| 1. |
- Maróti, Zoltán, et al.
(author)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Journal article (peer-reviewed)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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| 2. |
- Kotmayer, L, et al.
(author)
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Landscape of BCL2 Resistance Mutations in a Real-World Cohort of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax
- 2023
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 24:6
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Journal article (peer-reviewed)abstract
- The oral, highly selective Bcl2 inhibitor venetoclax has substantially improved the therapeutic landscape of chronic lymphocytic leukemia (CLL). Despite the remarkable response rates in patients with relapsed/refractory (R/R) disease, acquired resistance is the leading cause of treatment failure, with somatic BCL2 mutations being the predominant genetic drivers underpinning venetoclax resistance. To assess the correlation between disease progression and the most common BCL2 mutations G101V and D103Y, sensitive (10−4) screening for the most common BCL2 mutations G101V and D103Y was performed in 67 R/R CLL patients during venetoclax single-agent or venetoclax–rituximab combination therapy. With a median follow-up time of 23 months, BCL2 G101V and D103Y were detected in 10.4% (7/67) and 11.9% (8/67) of the cases, respectively, with four patients harboring both resistance mutations. Ten out of eleven patients carrying BCL2 G101V and/or D103Y experienced relapse during the follow-up period, representing 43.5% of the cases (10/23) showing clinical signs of disease progression. All BCL2 G101V or D103Y variants were detected in patients receiving venetoclax as a continuous single-agent treatment while these mutations were not observed during or after fixed-duration venetoclax therapy. Targeted ultra-deep sequencing of BCL2 uncovered three additional variants in four patient samples obtained at relapse, suggesting convergent evolution and implying a cooperating role of BCL2 mutations in driving venetoclax resistance. This cohort is the largest R/R CLL patient population reported to date in which BCL2 resistance mutations were investigated. Our study demonstrates the feasibility and clinical value of sensitive screening for BCL2 resistance mutations in R/R CLL.
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| 4. |
- Széles, Lajos, et al.
(author)
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Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.
- 2010
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In: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 24, s. 2218-2231
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Journal article (peer-reviewed)abstract
- Retinoid X receptors (RXRs) are heterodimerization partners for many nuclear receptors and also act as homodimers. Heterodimers formed by RXR and a nonpermissive partner, e.g. retinoic acid receptor (RAR) and vitamin D receptor (VDR), can be activated only by the agonist of the partner receptor. In contrast, heterodimers that contain permissive partners, e.g. liver X receptor (LXR) and peroxisome proliferator-activated receptor (PPAR), can be activated by agonists for either the partner receptor or RXR, raising the possibility of pleiotropic RXR signaling. However, it is not known to what extent the receptor's activation results in triggering mechanisms dependent or independent of permissive heterodimers. In this study, we systematically and quantitatively characterized all probable RXR-signaling pathways in differentiating human monocyte-derived dendritic cells (Mo-DCs). Using pharmacological, microarray and quantitative RT-PCR techniques, we identified and characterized gene sets regulated by RXR agonists (LG100268 and 9-cis retinoic acid) and agonists for LXRs, PPARs, RARα, and VDR. Our results demonstrated that permissiveness was partially impaired in Mo-DCs, because a large number of genes regulated by PPAR or LXR agonists was not affected by RXR-specific agonists or was regulated to a lesser extent. As expected, we found that RXR agonists regulated only small portions of RARα or VDR targets. Importantly, we could identify and characterize PPAR- and LXR-independent pathways in Mo-DCs most likely mediated by RXR homodimers. These data suggested that RXR signaling in Mo-DCs was mediated via multiple permissive heterodimers and also by mechanism(s) independent of permissive heterodimers, and it was controlled in a cell-type and gene-specific manner.
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| 5. |
- Balz, Reto, 1985, et al.
(author)
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Experimental and numerical investigation of cavitation in marine Diesel injectors
- 2021
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In: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310. ; 169
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Journal article (peer-reviewed)abstract
- To further increase the efficiency and decrease emissions of large two-stroke marine Diesel engines, the understanding of the fuel injection, spray breakup and the resulting combustion plays a vital role. Investigations have shown that the strongly asymmetrically and eccentrically arranged nozzle bores of the fuel injectors can lead to undesirable spray deflections that provoke increased component temperatures, emissions and fuel consumption. In order to investigate the origin of these spray deviations, transparent nozzles have been used to qualitatively visualize the in-nozzle flow under realistic geometrical and fuel pressure conditions. Three different, 0.75 mm diameter, single-hole nozzle geometries that represent typical geometrical characteristics have been used in cavitating nozzle flow experiments. The optical measurement technique Shadowgraphy has been applied to visualize the in-nozzle flow over the complete fuel injection process. The experiments have been performed with Diesel fuel at a rail pressure of 50 MPa with ambient back-pressure and temperature. Impingement measurements have been executed to compare the nozzle performance and validate CFD simulations using URANS with cavitation modeling in order to provide qualitative and quantitative support to the experimental results. The volume of fluid (VOF) method has been applied to simulate the multiphase flow with High Resolution Interface Capturing (HRIC). The cavitation model is based on a flash-boiling method with rapid heat transfer between the liquid and vapor phases. A Homogeneous Relaxation Model (HRM) has been utilized to describe the rate at which the instantaneous quality, the mass fraction of vapor in a two-phase mixture, will approach its equilibrium value. The numerical modeling of the cavitation inside the nozzle bore and the evaluated momentum flux have been compared to the experimental findings and show good agreement for the qualitative comparison of the cavitation patterns and differences of less than 6% for the quantitative momentum flux comparison.
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| 8. |
- Dévai, Gergely, et al.
(author)
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Efficient Code Generation from the High-level Domain-specific Language Feldspar for DSPs
- 2010
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In: 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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Conference paper (peer-reviewed)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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| 9. |
- Fischer, Peter, et al.
(author)
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Towards a 100 TW, sub-5-fs Optical Parametric Synthesizer
- 2020
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In: <em>OSA High-brightness Sources and Light-driven Interactions Congress 2020 (EUVXRAY, HILAS, MICS)</em>. - : Optical Society of America. - 9781943580736
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Conference paper (peer-reviewed)abstract
- We report on details of a peak-power upgrade of a sub-5-fs Optical Parametric Synthesizer towards 100TW. System design, pump pulse delaying and relay imaging system arepresented. A tailored second and third harmonic generation reaches conversion efficiencies of 80% and 60% with 80ps pump pulses.
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| 10. |
- Garamszegi, László Zsolt, et al.
(author)
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Evolution of relative brain size in dogs—no effects of selection for breed function, litter size, or longevity
- 2023
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In: Evolution. - 0014-3820 .- 1558-5646. ; 77:7, s. 1591-1606
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Journal article (peer-reviewed)abstract
- Domestication is a well-known example of the relaxation of environmentally based cognitive selection that leads to reductions in brain size. However, little is known about how brain size evolves after domestication and whether subsequent directional/artificial selection can compensate for domestication effects. The first animal to be domesticated was the dog, and recent directional breeding generated the extensive phenotypic variation among breeds we observe today. Here we use a novel endocranial dataset based on high-resolution CT scans to estimate brain size in 159 dog breeds and analyze how relative brain size varies across breeds in relation to functional selection, longevity, and litter size. In our analyses, we controlled for potential confounding factors such as common descent, gene flow, body size, and skull shape. We found that dogs have consistently smaller relative brain size than wolves supporting the domestication effect, but breeds that are more distantly related to wolves have relatively larger brains than breeds that are more closely related to wolves. Neither functional category, skull shape, longevity, nor litter size was associated with relative brain size, which implies that selection for performing specific tasks, morphology, and life history does not necessarily influence brain size evolution in domesticated species.
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