| 1. |
- 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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| 2. |
- Kovacs-Krausz, Zoltan, et al.
(författare)
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Revealing the band structure of ZrTe5 using multicarrier transport
- 2023
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 107:7
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Tidskriftsartikel (refereegranskat)abstract
- The layered material ZrTe5 appears to exhibit several exotic behaviors, which resulted in significant interest recently, although the exact properties are still highly debated. Among these we find a Dirac/Weyl semimetallic behavior, nontrivial spin textures revealed by low-temperature transport, and a potential weak or strong topological phase. The anomalous behavior of resistivity has been recently elucidated as originating from band shifting in the electronic structure. Our work examines magnetotransport behavior in ZrTe5 samples in the context of multicarrier transport. The results, in conjunction with ab initio band structure calculations, indicate that many of the transport features of ZrTe5 across the majority of the temperature range can be adequately explained by the semiclassical multicarrier transport model originating from a complex Fermi surface.
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| 3. |
- 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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| 4. |
- Cinege, Gyöngyi, et al.
(författare)
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Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insects have specialized cell types that participate in the elimination of parasites, for instance, the lamellocytes of the broadly studied species Drosophila melanogaster. Other drosophilids, such as Drosophila ananassae and the invasive Zaprionus indianus, have multinucleated giant hemocytes, a syncytium of blood cells that participate in the encapsulation of the eggs or larvae of parasitoid wasps. These cells can be formed by the fusion of hemocytes in circulation or originate from the lymph gland. Their ultrastructure highly resembles that of the mammalian megakaryocytes.Methods: Morphological, protein expressional, and functional features of blood cells were revealed using epifluorescence and confocal microscopy. The respective hemocyte subpopulations were identified using monoclonal antibodies in indirect immunofluorescence assays. Fluorescein isothiocyanate (FITC)-labeled Escherichia coli bacteria were used in phagocytosis tests. Gene expression analysis was performed following mRNA sequencing of blood cells.Results: D. ananassae and Z. indianus encapsulate foreign particles with the involvement of multinucleated giant hemocytes and mount a highly efficient immune response against parasitoid wasps. Morphological, protein expressional, and functional assays of Z. indianus blood cells suggested that these cells could be derived from large plasmatocytes, a unique cell type developing specifically after parasitoid wasp infection. Transcriptomic analysis of blood cells, isolated from naïve and wasp-infected Z. indianus larvae, revealed several differentially expressed genes involved in signal transduction, cell movements, encapsulation of foreign targets, energy production, and melanization, suggesting their role in the anti-parasitoid response. A large number of genes that encode proteins associated with coagulation and wound healing, such as phenoloxidase activity factor-like proteins, fibrinogen-related proteins, lectins, and proteins involved in the differentiation and function of platelets, were constitutively expressed. The remarkable ultrastructural similarities between giant hemocytes and mammalian megakaryocytes, and presence of platelets, and giant cell-derived anucleated fragments at wound sites hint at the involvement of this cell subpopulation in wound healing processes, in addition to participation in the encapsulation reaction.Conclusion: Our observations provide insights into the broad repertoire of blood cell functions required for efficient defense reactions to maintain the homeostasis of the organism. The analysis of the differentiation and function of multinucleated giant hemocytes gives an insight into the diversification of the immune mechanisms.
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| 5. |
- Maria, Csidey, et al.
(författare)
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Congenital aniridia patients experience on their visual impairment in Hungary An ANIRIDIA-NET survey
- 2023
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Ingår i: ORVOSI HETILAP. - : AKADEMIAI KIADO ZRT. - 0030-6002. ; 164:34, s. 1342-1349
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Aniridia is a rare congenital panocular disease associated with varying degrees of visual acuity impair-ment. Objective: To assess the experiences of congenital aniridia patients in Hungary, with visual impairment using a ques-tionnaire developed by the ANIRIDIA-NET. Patients and method: Patients completed the Hungarian version of the 20-item ANIRIDIA-NET questionnaire with our assistance. The questionnaire covered demographic data, the most common complaints caused by the disease, the difficulties caused by low vision in different life situations and the frequency of low vision aids used in daily life. Results: 33 subjects (17 female [51.51%] and 16 male [48.48%]), 16 (48.5%) children and 17 (51.5%) adults com-pleted the questionnaire, with an age of 25.69 +/- 17.49 years (5-59 years). Daily photosensitivity was reported by 27 (81.8%), dry eyes by 5 (15.2%), tearing by 4 (12.1%), fluctuating vision by 3 (9.1%), and eye pain by 2 (6.1%) sub-jects. The majority of respondents said that personal communication with schoolmates (16 [48.5%]) or colleagues at work (11 [33.3%]) never caused difficulties because of their visual impairment. 29 people (87.9%) never needed help with daily routines at home, 24 (72.7%) with getting to school/work and 17 (51.5%) with various activities. 29 peo-ple (87.8%) never used low vision aids for communication, 23 (69.7%) for travelling, 20 (60.6%) for participating in social activities, 18 (54.5%) for studying/work. Conclusion: Although aniridia is associated with reduced visual acuity, the majority of people with congenital aniridia, especially in childhood, manage to cope with personal communication and various life situations without difficulty, despite their eye complaints. Low vision aids can be an important aid for them as they grow into adulthood and as they age.
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| 6. |
- May, Ross
(författare)
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On the Feasibility of Reinforcement Learning in Single- and Multi-Agent Systems : The Cases of Indoor Climate and Prosumer Electricity Trading Communities
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Over half of the world’s population live in urban areas, a trend which is expected to only grow as we move further into the future. With this increasing trend in urbanisation, challenges are presented in the form of the management of urban infrastructure systems. As an essential infrastructure of any city, the energy system presents itself as one of the biggest challenges. Indeed, as cities expand in population and economically, global energy consumption increases, and as a result, so do greenhouse gas (GHG) emissions. Key to realising the goals as laid out by the 2030 Agenda for Sustainable Development, is the energy transition - embodied in the goals pertaining to affordable and clean energy, sustainable cities and communities, and climate action. Renewable energy systems (RESs) and energy efficiency have been shown as key strategies towards achieving these goals. While the building sector is considered to be one of the biggest contributors to climate change, it is also seen as an area with many opportunities for realising the energy transition. Indeed, the emergence of the smart city and the internet of things (IoT), alongside Photovoltaic and battery technology, offers opportunities for both the smart management of buildings, as well as the opportunity to form self-sufficient peer-to-peer (P2P) electricity trading communities. Within this context, advanced building control offers significant potential for mitigating global warming, grid instability, soaring energy costs, and exposure to poor indoor building climates. Most advanced control strategies, however, rely on complex mathematical models, which require a great deal of expertise to construct, thereby costing in time and money, and are unlikely to be frequently updated - which can lead to sub-optimal or even wrong performance. Furthermore, arriving at solutions in economic settings as complex and dynamic as the P2P electricity markets referred to above, often leads to solutions that are computationally intractable. A model-based approach thus seems, as alluded to above, unsustainable, and I thus propose taking a model-free alternative instead. One such alternative is the reinforcement learning (RL) method. This method provides a beautiful solution that addresses many of the limitations seen in more classical approaches - those based on complex mathematical models - to single- and multi-agent systems. To address the feasibility of RL in the context of building systems, I have developed four papers. In studying the literature, while there is much review work in support of RL for controlling energy consumption, it was found that there were no such works analysing RL from a methodological perspective w.r.t. controlling the comfort level of building occupants. Thus, in Paper I, to fill in this gap in knowledge, a comprehensive review in this area was carried out. To follow up, in Paper II, a case study was conducted to further assess, among other things, the computational feasibility of RL for controlling occupant comfort in a single agent context. It was found that the RL method was able to improve thermal and indoor air quality by more than 90% when compared with historically observed occupant data. Broadening the scope of RL, Papers III and IV considered the feasibility of RL at the district scale by considering the efficient trade of renewable electricity in a peer-to-peer prosumer energy market. In particular, in Paper III, by extending an open source economic simulation framework, multi-agent reinforcement learning (MARL) was used to optimise a dynamic price policy for trading the locally produced electricity. Compared with a benchmark fixed price signal, the dynamic price mechanism arrived at by RL, increased community net profit by more than 28%, and median community self-sufficiency by more than 2%. Furthermore, emergent social-economic behaviours such as changes in supply w.r.t changes in price were identified. A limitation of Paper III, however, is that it was conducted in a single environment. To address this limitation and to assess the general validity of the proposed MARL-solution, in Paper IV a full factorial experiment based on the factors of climate - manifested in heterogeneous demand/supply profiles and associated battery parameters, community scale, and price mechanism, was conducted in order to ascertain the response of the community w.r.t net-loss (financial gain), self-sufficiency, and income equality from trading locally produced electricity. The central finding of Paper IV was that the community, w.r.t net-loss, performs significantly better under a learned dynamic price mechanism than under the benchmark fixed price mechanism, and furthermore, a community under such a dynamic price mechanism stands an odds of 2 to 1 in increased financial savings.
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| 7. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 8. |
- Pethő, Dávid, et al.
(författare)
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Ferryl hemoglobin and heme induce Α1‐microglobulin in hemorrhaged atherosclerotic lesions with inhibitory function against hemoglobin and lipid oxidation
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:13
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Tidskriftsartikel (refereegranskat)abstract
- Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α1‐microglobulin (A1M) is a radical‐scavenging and heme‐binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions. Using immunohistochemistry, we observed a significant A1M immunoreactivity in atheromas and hemorrhaged plaques of carotid arteries in smooth muscle cells (SMCs) and macrophages. The most prominent expression was detected in macrophages of organized hemorrhage. To reveal a possible inducer of A1M expression in ruptured lesions, we exposed aortic endothelial cells (ECs), SMCs and macrophages to heme, Oxy‐ and FerrylHb. Both heme and FerrylHb, but not OxyHb, upregulated A1M mRNA expression in all cell types. Importantly, only FerrylHb induced A1M protein secretion in aortic ECs, SMCs and macrophages. To assess the possible function of A1M in ruptured lesions, we analyzed Hb oxidation and heme‐catalyzed lipid peroxidation in the presence of A1M. We showed that recombinant A1M markedly inhibited Hb oxidation and heme‐driven oxidative modification of low‐density lipoproteins as well plaque lipids derived from atheromas. These results demonstrate the presence of A1M in atherosclerotic plaques and suggest its induction by heme and FerrylHb in the resident cells.
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