| 1. |
- Dévai, Gergely, et al.
(författare)
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Efficient Code Generation from the High-level Domain-specific Language Feldspar for DSPs
- 2010
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Ingår i: ODES-8: 8th Workshop on Optimizations for DSP and Embedded Systems, workshop associated with IEEE/ACM International Symposium on Code Generation and Optimization (CGO).
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Konferensbidrag (refereegranskat)abstract
- Software for digital signal processors (DSPs) is traditionally highly hardware-dependent and hence porting it to new processors usually requires significant design effort. In this paper we present Feldspar (Functional Embedded Language for DSP and Parallelism), an embedded, high-level, domain-specific language for DSP algorithm design and the compilation techniques we developed for generating C code from specifications written in Feldspar. While Feldspar allows description of algorithms on specification level, we show that with the right set of abstractions and transformations this high level, functional specification can be transformed into C code that is comparable or better than reference, hand-crafted C language implementations. The Feldspar compiler is highly modular and plugin-based, hence future hardware-specific plugins will enable automatic generation of efficient, hardware-specific code. This approach enables the encapsulation of knowledge of hardware completely in the compiler and thus allows description of algorithms in completely hardware-independent, portable manner.
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| 2. |
- Gulyas, Katalin, et al.
(författare)
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Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis
- 2020
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 39:1, s. 167-175
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesRheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS.Patients and methodsThirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months.ResultsTNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP.ConclusionsAnti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.
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| 3. |
- Juhasz, Balazs, et al.
(författare)
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Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients
- 2021
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central (BMC). - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. Methods Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. Results We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. Conclusions BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect.
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| 4. |
- Axelsson, Emil, 1978, et al.
(författare)
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Feldspar: A Domain Specific Language for Digital Signal Processing algorithms
- 2010
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Ingår i: Eighth ACM/IEEE International Conference on Formal Methods and Models for Codesign. - 9781424478859 ; , s. 169-178
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Konferensbidrag (refereegranskat)abstract
- A new language, Feldspar, is presented, enabling high-level and platform-independent description of digital signal processing (DSP) algorithms. Feldspar is a pure functional language embedded in Haskell. It offers a high-level dataflow style of programming, as well as a more mathematical style based on vector indices. The key to generating efficient code from such descriptions is a high-level optimization technique called vector fusion. Feldspar is based on a low-level, functional core language which has a relatively small semantic gap to machine-oriented languages like C. The core language serves as the interface to the back-end code generator, which produces C. For very small examples, the generated code performs comparably to hand-written C code when run on a DSP target. While initial results are promising, to achieve good performance on larger examples, issues related to memory access patterns and array copying will have to be addressed.
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| 5. |
- Bott, Lukas Thomas, et al.
(författare)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Konferensbidrag (refereegranskat)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 6. |
- Büki, Andras, 1966-, et al.
(författare)
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Peptidergic innervation of human cerebral blood vessels and saccular aneurysms
- 1999
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Ingår i: Acta Neuropathologica. - : Springer. - 0001-6322 .- 1432-0533. ; 98:4, s. 383-388
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Tidskriftsartikel (refereegranskat)abstract
- Peptidergic innervation of the human cerebral vasculature has not yet been described in detail and its role in the maintenance of cerebral autoregulation still needs to be established. Similarly, few data exist on the innervation of vascular malformations. The aim of this study was to clarify the peptidergic innervation patterns of human cerebral arteries of various sizes, and, for the first time, that of saccular aneurysms. Light microscopic study of whole-mount preparations of human cerebral arteries and aneurysm sacs resected either during tumor removal or after neck-clipping were carried out by means of silver-intensified light microscopic immunocytochemistry visualizing neuropeptide-Y, calcitonin gene-related peptide and substance P immunoreactivity. Systematic morphological investigations confirmed the presence of longitudinal fiber bundles on the adventitia and a network-like deeper peptidergic system at the adventitia-media border, while in smaller pial and intraparenchymal vessels, only sparse longitudinal immunopositive axons could be detected. The innervation pattern was totally absent in the wall of saccular aneurysms with the complete disappearance of peptidergic nerve fibers in some areas. To the best of our knowledge neither the disappearance of this network on small pial and intraparenchymal vessels, nor the absence of an innervation pattern in saccular aneurysms have been described before. Nonhomogeneous peptidergic innervation of the human cerebral vascular tree might be one of the factors responsible for the distinct autoregulatory properties of the capacitance and resistance vessels. Malfunction of this vasoregulatory system might lead to the impairment of autoregulation during pathological conditions such as subarachnoid hemorrhage.
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| 7. |
- Endrődi, Balázs, 1987-, et al.
(författare)
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Challenges and rewards of the electrosynthesis of macroscopic aligned carbon nanotube array/conducting polymer hybrid assemblies
- 2015
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Ingår i: Journal of Polymer Science Part B. - : Wiley. - 0887-6266 .- 1099-0488. ; 53, s. 1507-1518
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid assemblies based on conducting polymers and carbon nanomaterials with organized nanoscale structure are excellent candidates for various application schemes ranging from thermal management to electrochemical energy conversion and storage. In the case of macroscopic samples, however, precise control of the nanoscale structure has remained a major challenge to be solved for the scientific community. In this study we demonstrate possible routes to homogeneously infiltrate poly(3-hexylthiophene), poly(3,4-ethylenedioxythiophene), and polyaniline into macroscopic arrays of vertically aligned multiwalled carbon nanotubes (MWCNTAs). Electron microscopic images and Raman spectroscopic analysis (performed along the longitudinal dimension of the hybrid samples) both confirmed that optimization of the electropolymerization circumstances allowed fine tuning of the hybrid structure towards the targeted application. In this vein, three different application avenues were tested. The remarkable anisotropy in both the electrical and thermal conductivity of the nanocomposites makes them eminently attractive candidates to be deployed in thermal management. Thermoelectric studies, aimed to understand the effect of organized nanoscale morphology on the important parameters (Seebeck coefficient, electrical-, and thermal conductivity) compared to their non-organized hybrid counterparts. Finally, extraordinary high charge storage capacity values were registered for the MWCNTA/PANI hybrids (500 F g−1 and 1–3 F cm−2).
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| 8. |
- Fülöp, Katalin, et al.
(författare)
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Arabidopsis anaphase-promoting complexes : multiple activators and wide range of substrates might keep APC perpetually busy
- 2005
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Ingår i: Cell Cycle. - Austin : Landes bioscience. - 1538-4101 .- 1551-4005. ; 4:8, s. 1084-1092
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Tidskriftsartikel (refereegranskat)abstract
- The anaphase-promoting complex (APC), a multisubunit E3 ubiquitin ligase, is an essential regulator of the cell cycle from metaphase until S phase in yeast and metazoans. APC mediates degradation of numerous cell cycle-related proteins, including mitotic cyclins and its activation and substrate-specificity are determined by two adaptor proteins, Cdc20 and Cdh1. Plants have multiple APC activators and the Cdh1-type proteins, in addition, are represented by two subclasses, known as Ccs52A and Ccs52B. The Arabidopsis genome contains five cdc20 genes as well as ccs52A1, ccs52A2 and ccs52B.In Schizosaccharomyces pombe, expression of the three Atccs52 genes elicited distinct phenotypes supporting nonredundant function of the AtCcs52 proteins. Consistent with these activities, the AtCcs52 proteins were able to bind both to the yeast and the Arabidopsis APCs. In synchronized Arabidopsis cell cultures the cdc20 transcripts were present from early G2 until the M-phase exit, ccs52B from G2/M to M while ccs52A1 and ccs52A2 were from late M until early G2, suggesting consecutive action of these APC activators in the plant cell cycle. The AtCcs52 proteins interacted with different subsets of mitotic cyclins, in accordance with their expression profiles, either in free- or CDK-bound forms. Expression of most APC subunits was constitutive, whereas cdc27a and cdc27b, corresponding to two forms of apc3, and ubc19 and ubc20 encoding E2-C type ubiquitin-conjugating enzymes displayed differences in their cell cycle regulation. These data indicate the existence of numerous APC(Cdc20/Ccs52/Cdc27) forms in Arabidopsis, which in conjunction with different E2 enzymes might have distinct or complementary functions at distinct stages of the cell cycle.
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| 9. |
- Hardisty, Alex R., et al.
(författare)
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BioVeL: A virtual laboratory for data analysis and modelling in biodiversity science and ecology
- 2016
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Ingår i: BMC Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 The Author(s).Background: Making forecasts about biodiversity and giving support to policy relies increasingly on large collections of data held electronically, and on substantial computational capability and capacity to analyse, model, simulate and predict using such data. However, the physically distributed nature of data resources and of expertise in advanced analytical tools creates many challenges for the modern scientist. Across the wider biological sciences, presenting such capabilities on the Internet (as "Web services") and using scientific workflow systems to compose them for particular tasks is a practical way to carry out robust "in silico" science. However, use of this approach in biodiversity science and ecology has thus far been quite limited. Results: BioVeL is a virtual laboratory for data analysis and modelling in biodiversity science and ecology, freely accessible via the Internet. BioVeL includes functions for accessing and analysing data through curated Web services; for performing complex in silico analysis through exposure of R programs, workflows, and batch processing functions; for on-line collaboration through sharing of workflows and workflow runs; for experiment documentation through reproducibility and repeatability; and for computational support via seamless connections to supporting computing infrastructures. We developed and improved more than 60 Web services with significant potential in many different kinds of data analysis and modelling tasks. We composed reusable workflows using these Web services, also incorporating R programs. Deploying these tools into an easy-to-use and accessible 'virtual laboratory', free via the Internet, we applied the workflows in several diverse case studies. We opened the virtual laboratory for public use and through a programme of external engagement we actively encouraged scientists and third party application and tool developers to try out the services and contribute to the activity. Conclusions: Our work shows we can deliver an operational, scalable and flexible Internet-based virtual laboratory to meet new demands for data processing and analysis in biodiversity science and ecology. In particular, we have successfully integrated existing and popular tools and practices from different scientific disciplines to be used in biodiversity and ecological research.
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| 10. |
- Horváth, Beatrix M, et al.
(författare)
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EBP1 regulates organ size through cell growth and proliferation in plants.
- 2006
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:20, s. 4909-20
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Tidskriftsartikel (refereegranskat)abstract
- Plant organ size shows remarkable uniformity within species indicating strong endogenous control. We have identified a plant growth regulatory gene, functionally and structurally homologous to human EBP1. Plant EBP1 levels are tightly regulated; gene expression is highest in developing organs and correlates with genes involved in ribosome biogenesis and function. EBP1 protein is stabilised by auxin. Elevating or decreasing EBP1 levels in transgenic plants results in a dose-dependent increase or reduction in organ growth, respectively. During early stages of organ development, EBP1 promotes cell proliferation, influences cell-size threshold for division and shortens the period of meristematic activity. In postmitotic cells, it enhances cell expansion. EBP1 is required for expression of cell cycle genes; CyclinD3;1, ribonucleotide reductase 2 and the cyclin-dependent kinase B1;1. The regulation of these genes by EBP1 is dose and auxin dependent and might rely on the effect of EBP1 to reduce RBR1 protein level. We argue that EBP1 is a conserved, dose-dependent regulator of cell growth that is connected to meristematic competence and cell proliferation via regulation of RBR1 level.
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| 11. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 12. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 13. |
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| 14. |
- Magyar, Zoltan, et al.
(författare)
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Arabidopsis E2FA stimulates proliferation and endocycle separately through RBR-bound and RBR-free complexes
- 2012
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Ingår i: EMBO Journal. - New York, NY, USA : Nature Publishing Group. - 0261-4189 .- 1460-2075. ; 31:6, s. 1480-1493
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Tidskriftsartikel (refereegranskat)abstract
- Post-embryonic growth in plants depends on the continuous supply of undifferentiated cells within meristems. Proliferating cells maintain their competence for division by active repression of differentiation and the associated endocycle entry. We show by upregulation and downregulation of E2FA that it is required for maintaining proliferation, as well as for endocycle entry. While E2FB-RBR1 (retinoblastoma-related protein 1) complexes are reduced after sucrose addition or at elevated CYCD3;1 levels, E2FA maintains a stable complex with RBR1 in proliferating cells. Chromatin immunoprecipitation shows that RBR1 binds in the proximity of E2F promoter elements in CCS52A1 and CSS52A2 genes, central regulators for the switch from proliferation to endocycles. Overexpression of a truncated E2FA mutant (E2FA(Delta RB)) lacking the RBR1-binding domain interferes with RBR1 recruitment to promoters through E2FA, leading to decreased meristem size in roots, premature cell expansion and hyperactivated endocycle in leaves. E2F target genes, including CCS52A1 and CCS52A2, are upregulated in E2FADRB and e2fa knockout lines. These data suggest that E2FA in complex with RBR1 forms a repressor complex in proliferating cells to inhibit premature differentiation and endocycle entry. Thus, E2FA regulates organ growth via two distinct, sequentially operating pathways. The EMBO Journal (2012) 31, 1480-1493. doi:10.1038/emboj.2012.13; Published online 3 February 2012
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| 15. |
- Maróti, Zoltán, et al.
(författare)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Tidskriftsartikel (refereegranskat)abstract
- Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this “immigrant core” of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common “proto-Ugric” gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring “native European” ancestry.
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| 16. |
- Motte, Damien, et al.
(författare)
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Assessment framework for a methodology under development – Application to the PDA methodology
- 2016
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Ingår i: Proceedings of the 11th International Symposium on Tools and Methods of Competitive Engineering - TMCE'16. - 9789461866356 ; , s. 373-388
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Konferensbidrag (refereegranskat)abstract
- This paper presents an assessment framework for methodologies under development. It is adapted from the evaluation framework for the design of an engineering model developed by Ben Ahmed and colleagues [1]. The assessment framework allows to take into account in a systematic way characteristics (that is, main categories or classes of potential requirements) that are of importance for the assessment of the quality a methodology, beyond effectiveness and efficiency. The framework is intended to be employed similarly to engineering design requirements checklists: ensuring first that no important characteristics are left out; deriving from these characteristics more specific requirements when necessary; using these characteristics or the derived requirements both to drive the development of the methodology and as evaluation criteria to assess the elements of the developed methodology. These characteristics can then be screened again as the methodology is improved. As the methodology is being developed, the assessments can go from wide and qualitative to more stringent. The framework is applied to assess the predictive design analysis (PDA) methodology.[1] Ben Ahmed, W., Mekhilef, M., Yannou, B., and Bigand, M., (2010), "Evaluation framework for the design of an engineering model", Artificial Intelligence for Engineering Design, Analysis and Manufacturing, 24(1), pp. 107-125.
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| 17. |
- Motte, Damien, et al.
(författare)
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Integration of the computer-based design analysis activity in the engineering design process - A literature survey
- 2014
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Ingår i: Proceedings of the 10th International Symposium on Tools and Methods of Competitive Engineering - TMCE'14. - Delft : Delft University of Technology. - 9789461861771 - 9461861761 - 9789461861764 ; 2, s. 1181-1194
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Konferensbidrag (refereegranskat)abstract
- Computer-based design analysis is nowadays a common activity in most development projects. Used for design evaluation, verification, validation, or as a support for design exploration, it fulfils an important support function for the engineering designer, thus making it essential to have an operationally efficient and effective integration between both the engineering design and design analysis activities in the overall development project. In this area, most works are focusing on software (mainly CAD/CAE) integra-tion, but not on the integration between computer-based design analysis and engineering design at the process level or on the collaboration between the engineering designer and the design analyst. This paper presents a review of the literature on that specific topic, namely the integration of the computer-based design analysis activity in the engineering design process. Different research topics are identified and elaborated upon: integration in general process models; rec-ommendations for the different analysis steps; analysis early in the engineering design process; integration of design analysis in the engineering designer's work; alternative usages of design analysis in the engineering design process; and others, such as recommending guidelines instead of process models, quality assurance aspects, education, and implementation issues. Some neglected aspects were also identified. Among others, there is a lack of research into the so-called technology development (development of design analysis procedures and guidelines), and a need for emphasis on uncertainties, both coupled with the design analysis activity.
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| 18. |
- Pusztai, Anita, et al.
(författare)
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Associations of vascular and bone status in arthritis patients
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease.
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| 19. |
- Romanov, Roman A., et al.
(författare)
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Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
- 2017
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 20:2, s. 176-188
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Tidskriftsartikel (refereegranskat)abstract
- The hypothalamus contains the highest diversity of neurons in the brain. Many of these neurons can co-release neurotransmitters and neuropeptides in a use-dependent manner. Investigators have hitherto relied on candidate protein-based tools to correlate behavioral, endocrine and gender traits with hypothalamic neuron identity. Here we map neuronal identities in the hypothalamus by single-cell RNA sequencing. We distinguished 62 neuronal subtypes producing glutamatergic, dopaminergic or GABAergic markers for synaptic neurotransmission and harboring the ability to engage in task-dependent neurotransmitter switching. We identified dopamine neurons that uniquely coexpress the Onecut3 and Nmur2 genes, and placed these in the periventricular nucleus with many synaptic afferents arising from neuromedin S+ neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S+ inputs originate from neurons expressing Per2 and Per3 and their tyrosine hydroxylase phosphorylation is regulated in a circadian fashion. Overall, our catalog of neuronal subclasses provides new understanding of. hypothalamic organization and function.
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| 20. |
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| 21. |
- Szucs, Edina, et al.
(författare)
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Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives
- 2020
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Ingår i: European Journal of Medicinal Chemistry. - : ELSEVIER. - 0223-5234 .- 1768-3254. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Morphine and its derivatives play inevitably important role in the m-opioid receptor (MOR) targeted antinociception. A structure-activity relationship study is presented for novel and known orvinol and thevinol derivatives with varying 3-O, 6-O, 17-N and 20-alkyl substitutions starting from agonists, antagonists and partial agonists. In vitro competition binding experiments with [H-3]DAMGO showed low subnanomolar affinity to MOR. Generally, 6-O-demethylation increased the affinity toward MOR and decreased the efficacy changing the pharmacological profile in some cases. In vivo tests in osteoarthritis inflammation model showed significant antiallodynic effects of thevinol derivatives while orvinol derivatives did not. The pharmacological character was modelled by computational docking to both active and inactive state models of MOR. Docking energy difference for the two states separates agonists and antagonists well while partial agonists overlapped with them. An interaction pattern of the ligands, involving the interacting receptor atoms, showed more efficient separation of the pharmacological profiles. In rats, thevinol derivatives showed antiallodynic effect in vivo. The orvinol derivatives, except for 6-O-desmethyl-dihydroetorfin (2c), did not show antiallodynic effect.
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| 22. |
- Toth, Luca, et al.
(författare)
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The Effect of Mild Traumatic Brain Injury on Cerebral Microbleeds in Aging
- 2021
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- A traumatic brain injury (TBI) induces the formation of cerebral microbleeds (CMBs), which are associated with cognitive impairments, psychiatric disorders, and gait dysfunctions in patients. Elderly people frequently suffer TBIs, especially mild brain trauma (mTBI). Interestingly, aging is also an independent risk factor for the development of CMBs. However, how TBI and aging may interact to promote the development of CMBs is not well established. In order to test the hypothesis that an mTBI exacerbates the development of CMBs in the elderly, we compared the number and cerebral distribution of CMBs and assessed them by analysing susceptibility weighted (SW) MRI in young (25 +/- 10 years old, n = 18) and elder (72 +/- 7 years old, n = 17) patients after an mTBI and in age-matched healthy subjects (young: 25 +/- 6 years old, n = 20; aged: 68 +/- 5 years old, n = 23). We found significantly more CMBs in elder patients after an mTBI compared with young patients; however, we did not observe a significant difference in the number of cerebral microhemorrhages between aged and aged patients with mTBI. The majority of CMBs were found supratentorially (lobar and basal ganglion). The lobar distribution of supratentorial CMBs showed that aging enhances the formation of parietal and occipital CMBs after mTBIs. This suggests that aging and mTBIs do not synergize in the induction of the development of CMBs, and that the different distribution of mTBI-induced CMBs in aged patients may lead to specific age-related clinical characteristics of mTBIs.
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| 23. |
- Toth, Luca, et al.
(författare)
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Traumatic brain injury-induced cerebral microbleeds in the elderly
- 2021
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Ingår i: GeroScience. - : Springer. - 2509-2715 .- 2509-2723. ; 43:1, s. 125-136
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) was shown to lead to the development of cerebral microbleeds (CMBs), which are associated with long term cognitive decline and gait disturbances in patients. The elderly is one of the most vulnerable parts of the population to suffer TBI. Importantly, ageing is known to exacerbate microvascular fragility and to promote the formation of CMBs. In this overview, the effect of ageing is discussed on the development and characteristics of TBI-related CMBs, with special emphasis on CMBs associated with mild TBI. Four cases of TBI-related CMBs are described to illustrate the concept that ageing exacerbates the deleterious microvascular effects of TBI and that similar brain trauma may induce more CMBs in old patients than in young ones. Recommendations are made for future prospective studies to establish the mechanistic effects of ageing on the formation of CMBs after TBI, and to determine long-term consequences of CMBs on clinically relevant outcome measures including cognitive performance, gait and balance function.
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| 24. |
- Wagner, Michelle, et al.
(författare)
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ORAMA Project - D6-6 Technical Final Report and Recommendations
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Securing the sustainable access to and supply of raw materials, and particularly of Critical Raw Materials (CRM), is of high importance for the European economy. Complex primary and secondary resources contain many different raw materials. The inability to easily produce reliable statistics about reserves, resources, stocks, and flows of raw materials limits the understanding of global trends in resource availability and hampers formulation of mineral and waste policies. This ultimately affects supply chain security and strategic decisions by industry. Hence, it is an issue of great concern for the European Commission (EC) and many other stakeholders. The ORAMA project (Optimising quality of information in RAw MAterial data collection across Europe) seeks to contribute to better supply of raw materials by improving the quality of harmonised raw materials data collection and information sharing among the different levels within the European Union (EU). Data collection practices for primary and secondary raw materials (PRM and SRM) face specific challenges in EU Member States (MS). For PRM data, the main concerns are related to data availability, geographical coverage, accessibility, harmonisation, interoperability, quality, and thematic coverage. The reporting of primary mineral resources and reserves statistics is currently carried out by a wide variety of systems, standards or codes which are not directly comparable. Hence, it is currently impossible to produce reliable pan-European figures for resources for any mineral commodity. ORAMA addresses these issues by recommending a single standard for reporting of resource data, the United Nations Framework Classification (UNFC), a framework for reporting mineral resource data developed by the UN. To enable and encourage data providers to adopt this standard for European PRM data, the ORAMA project has developed resources in the form of a range of training materials and good practice examples. The ORAMA project demonstrates that the analysis of various classifications and reporting systems that sit within the INSPIRE (Infrastructure for Spatial Information in the European Community) concept and data services, are not opposing but rather integral elements of the proper European level data collection and production of information for PRM and SRM. The use of UNFC/UNRMS (United Nations Resource Management System) in the framework of the INSPIRE compliant data service can significantly contribute to sustainable resource management taking into account not only geological knowledge and raw materials potential but also environmental and social issues, based on using the national/regional legislative elements for exploration and exploitation as well. In the case of SRM, the challenges are somewhat different. Regarding mining waste (MIN), the lack of information on deposit characteristics (composition, volumes, and suitable processing technology) is a huge barrier in the identification of recovery potential of the valuable materials that remain in the waste. Furthermore, the lack of a single reporting standard commonly accepted at EU level has created a dispersion of existing information in various systems and project deliverables. In the case of electrical and electronic equipment (EEE) and batteries, beyond the lack of harmonisation, substantial data gaps exist for the market inputs, materials consumption and stocks, and for waste electrical and electronic equipment (WEEE) for unaccounted flows ending up being scavenged, metal scrap and export channels. For vehicles, huge amounts of data, both on stocks and flows and on composition, are systematically collected by authorities and the manufacturing industry, but are only publicly available in a somewhat too aggregated form (placed on market (POM), stock, waste flows) or not at all (composition data). Even when collected, the reporting of the composition of these flows on a product, component and materials level are currently poorly described across all MS, and when actually ending up in recycling processes, the recovery efficiency for all elements and CRMs, in particular, is disappointing. In order to improve the data collection and reporting practices for SRM a structured review and inventory were made followed by a data gap analysis which resulted in the developments of recommendations and subsequently the selection of 6 case studies. The SRM case studies tackle the main data gaps encountered in the analysis and developed tools that will enable the improvement and harmonisation of collection and reporting practices in MS, treatment facilities, data providers, academia among others. The ORAMA project recommends to establish more structured and continuous funding for realising and maintaining a European data infrastructure for tracking both PRM and SRM. The current project-by-project based financing is insufficient and not sustainable to properly track and understand Europe’s strengths and weaknesses in the early resource intensive stages of global supply chains.
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| 25. |
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