Rega Institute for Medical Research

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    263134 research outputs found

    Rethinking category selectivity: insights from the macaque inferior temporal cortex

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    Ritchie et al. argue that the traditional framework of category selectivity has limited value for understanding the organization of the ventral visual stream and propose shifting focus toward behavioral relevance and examining vision under naturalistic task conditions. While I agree with many of their points, I expand on their discussion of category selectivity, as well as the drivers of ventral stream organization, from a nonhuman primate perspective.sponsorship: R. V. was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [grant agreement No. 856495]. (European Research Council|856495, European Research Council (ERC)|856495)status: Published onlin

    Limits of Consent

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    status: Publishe

    Dynamic Referencing for 3D Localization of Fiber-Optic Shape Estimation in Endovascular Interventions

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    sponsorship: This work was supported in part by the European Union's H2020 Research and Innovation Program under Grant Agreement 101017140 (ARTERY), and in part by KU Leuven under Project C3/23/062 LumiSense and Project IDN/21/013 CURE. (European Union|101017140, KU Leuven|C3/23/062, KU Leuven|IDN/21/013)status: Publishe

    Phase relationship investigation of Cerium-Germanium binary system

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    sponsorship: This work is financially supported by the Fundamental Research Funds for the Central Universities (No. 2023MS025) , and the Natural Science Foundation of Hebei Province, China (No. E2024502020) . Thanks to the Royal Institute of Technology Sweden and CompuTherm LLC for supplying Thermo-Calc software and Pandat Software packages respectively. The contribution of Prof. Dr. Changrong Li on supervision of phase equilibrium analysis and thermodynamic optimization is greatly acknowledged. (Fundamental Research Funds for the Central Universities|2023MS025, Natural Science Foundation of Hebei Province, China|E2024502020)status: Publishe

    Coexistence of Longitudinal and Transverse Oscillations in Polar Plumes Observed with Solar Orbiter/Extreme Ultraviolet Imager

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    sponsorship: Solar Orbiter is a space mission of international collaboration between ESA and NASA, operated by ESA. The EUI instrument was built by CSL, IAS, MPS, MSSL/UCL, PMOD/WRC, ROB, and LCF/IO, with funding from the Belgian Federal Science Policy Office (BELSPO/PRODEX PEA 4000134088, 4000112292, and 4000106864); the Centre National d'Etudes Spatiales (CNES); the UK Space Agency (UKSA); the Bundesministerium fur Wirtschaft und Energie (BMWi), through the Deutsches Zentrum fur Luft- und Raumfahrt (DLR); and the Swiss Space Office (SSO). U.B. acknowledges the support from an EUI guest investigatorship. U.B. would like to thank Cis Verbeeck, Nancy Narang, and David Berghmans for their hospitality during her stay at ROB. V.P. is supported by a SERB startup research grant (File no. SRG/2022/001687). S.K.P. is grateful to SERB/ANRF for a startup research grant (No. SRG/2023/002623). N.N. is supported by the Belgian Federal Science Policy Office (BELSPO) through the contract B2/223/P1/CLOSE-UP. C.V. thanks BELSPO for the provision of financial support in the framework of the PRODEX Programme of the European Space Agency (ESA) under contract number 4000134088. T.V.D. was supported by the C1 grant TRACEspace of Internal Funds KU Leuven and a Senior Research Project (G088021N) of the FWO Vlaanderen. Furthermore, T.V.D. received financial support from the Flemish Government under the long-term structural Methusalem funding program, project SOUL: Stellar evolution in full glory, grant METH/24/012, at KU Leuven. This is also part of the DynaSun project and has thus received funding under the Horizon Europe program of the European Union under grant agreement no. 101131534. The views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union and therefore the European Union cannot be held responsible for them. T.V.D. would like to thank Vaibhav Pant and Krishna Prasad for their hospitality during his sabbatical stay at ARIES in spring 2025. The authors also acknowledge Dipankar Banerjee, Daye Lim, and the EUI team for their constructive comments. Finally, the authors wish to thank the reviewers for their valuable suggestions. (Belgian Federal Science Policy Office|BELSPO/PRODEX PEA 4000134088, Belgian Federal Science Policy Office|4000112292, Belgian Federal Science Policy Office|4000106864, Centre National d'Etudes Spatiales (CNES), UK Space Agency (UKSA), Bundesministerium fr Wirtschaft und Energie (BMWi), through the Deutsches Zentrum fr Luft- und Raumfahrt (DLR), Swiss Space Office (SSO), EUI guest investigatorship, SERB startup research grant|SRG/2022/001687, SERB startup research grant|SRG/2023/002623, Belgian Federal Science Policy Office (BELSPO)|B2/223/P1/CLOSE-UP, PRODEX Programme of the European Space Agency (ESA)|4000134088, C1 grant TRACEspace of Internal Funds KU Leuven|G088021N, FWO Vlaanderen, Flemish Government under the long-term structural Methusalem funding program, project SOUL: Stellar evolution in full glory|METH/24/012, Horizon Europe program of the European Union|101131534)status: Publishe

    Adaptive Transgenerational Effects Offset the Increased Toxicity of the Pesticide Chlorpyrifos under Heat Stress

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    Although the importance of transgenerational effects and multiple stressors in ecotoxicology is well-established, transgenerational interactions between toxicants and natural stressors remain largely unexplored, yet are critical for advancing ecological risk assessment. In this study, we exposed the water flea Daphnia magna to a heat spike (25 °C vs 32 °C) followed by exposure to chlorpyrifos at an environmentally relevant concentration (0.5 μg/L) across the parental and grand-offspring generations using a full-factorial design. In both generations, chlorpyrifos reduced survival and acute heat tolerance, which, as expected, were further magnified by the preceding heat spike. Notably, parental exposure to chlorpyrifos decreased the sensitivity of grand-offspring to the toxicant, and more strikingly, offset the synergistic interaction between the heat spike and chlorpyrifos. Both the increased toxicity of the pesticide after exposure to the heat spike and the mitigating impact of the transgenerational effects on this synergism could be explained by changes in acetylcholinesterase activity and hemoglobin concentration. These findings underscore the critical role of transgenerational effects in ecotoxicology, including their potential to shape toxicant-warming interactions. Our results emphasize the necessity of incorporating transgenerational effects and multistressor scenarios into ecological risk assessments of toxicants in the context of global warming.sponsorship: This study was supported by the Jing-Jin-Ji Regional Integrated Environmental Improvement-National Science and Technology Major Project of Ministry of Ecology and Environment of China (2025ZD1200800), National Natural Science Foundation of China (31800307 and 32471608), FWO grant (G.0144.23N), and KU Leuven C1 grant (C16/23/003). (Jing-Jin-Ji Regional Integrated Environmental Improvement - National Science and Technology Major Project of Ministry of Ecology and Environment of China|2025ZD1200800, KU Leuven C1 grant|C16/23/003, National Natural Science Foundation of China (NSFC)|31800307, 32471608, FWO grant|G.0144.23N)status: Publishe

    Deep transfer learning for codling moth damage detection in 'Conference' pear using X-ray radiography

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    sponsorship: We thank Gertie Peusens of pcfruit npo (Belgium) , KU Leuven XCT core facility and UZ Leuven for their collaboration and for supporting this research. The authors of this article also greatly appreciate the financial support of the Flanders Fund for Scientific Research (FWO Vlaanderen, SB Jiaqi He, 1SH8Q24N, Belgium) and VLAIO (SystControl project, HBC.2021.1069) . (Flanders Fund for Scientific Research (FWO Vlaanderen), Belgium|1SH8Q24N, VLAIO|HBC.2021.1069)status: Accepte

    Sec61-gerichte remmers van virale eiwitimport in het ER als antivirale middelen tegen orthoflavivirussen

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    The genus of Orthoflaviviruses includes mosquito-borne RNA viruses like dengue, Zika and yellow fever virus which impose a significant threat to global health. Dengue virus (DENV) is currently the most widespread arbovirus, endemic in more than 100 countries. Due to the spread of its Aedes vector, DENV is further expanding to new areas in Europe and the Americas. Infections by one of the four DENV serotypes manifest across a broad clinical spectrum, ranging from subclinical or self-limiting febrile illness to life-threatening severe dengue. At present, no FDA-approved specific antiviral treatment is available, and the safety of a vaccine against DENV is still on debate. The first chapter gives an overview of the role of the ER in DENV replication and describes the different ER translocation inhibitors. The endoplasmic reticulum (ER) plays a central role in orthoflaviviral infections, supporting multiple stages of the viral life cycle, including translation, post-translational modification, genome replication, and assembly. Integration of the orthoflaviviral polyprotein into the ER membrane is proposed to occur through the Sec61-dependent co-translational translocation pathway. Although inhibitors of Sec61-dependent translocation are considered as promising candidates for anti-cancer therapies or to treat several human diseases, their potential in the context of antiviral treatment has received limited attention. In the Vermeire lab, the small molecule inhibitors cyclotriazadisulfonamides (CADAs) have been discovered as a new class of Sec61 translocon inhibitors with high substrate selectivity. CADA interferes with Sec61-mediated co-translational protein translocation in a signal peptide (SP)-dependent manner. In this PhD project, we explored the antiviral potential of CADA derivatives against DENV and other orthoflaviviruses and studied the mode-of-action of CADAs as translocation inhibitors of DENV. In the first part of this project (chapter 4), we describe the antiviral activity for the CADA derivative Flavitransin (FT), previously named VGD020, against DENV serotype 2 (DENV2) in various cell lines and primary immune cells at sub-micromolar concentrations. Moreover, FT showed consistent antiviral activity against all four DENV serotypes, and also against Zika and yellow fever virus. In the second part of the project (chapter 5), we focus on the mode-of-action of FT. A time-of-drug addition assay suggested that FT interferes with a post-entry event of virus replication taking place between 4-8 hours post infection, in line with its anticipated Sec61 inhibition. Through a set of cell-transfection experiments and complimentary cell-free in vitro translation/translocation assays we could irrefutably demonstrate that FT specifically and selectively inhibits the first translocation step of the DENV polyprotein, i.e., the translocation of the pre-membrane protein. Additional cell-transfection experiments indicated that only the first (N-terminal) transmembrane domain (TMD), which serves as the main Sec61 targeting sequence of the viral nascent chain, conferred sensitivity to FT. In contrast, the more downstream SP-like TMD of the Envelope and Non-Structural protein 1 showed full resistance to FT. Combinational treatment of transfected cells with a proteasome inhibitor and FT, showed that upon FT treatment, a small fraction of the non-translocated protein is re-routed to the cytosol for proteasomal degradation. In the third and fourth part of this project (chapter 6 and 7), we mapped the complex interplay between FT, the Sec61 translocon (host), and the DENV targeting sequence. Selection and genotyping of FT-resistant HCT116 cells revealed a unique set of mutations in the Sec61α subunit e.g. A70V, E78A and L449F. In the presence of these mutations, FT's antiviral activity was diminished or completely abolished as verified in DENV-infected cells, transfected cells with DENV-reporter constructs, but also in a cell-free in vitro translation/translocation system. In addition, FT exerted a high barrier to the development of viral resistance. FT-desensitized DENV, obtained after a high number of passages under increasing FT pressure, had acquired multiple AA substitutions at different sites (also at the first TMD) throughout the polyprotein, but remained fully sensitive to high concentrations of FT. In the final chapter, we explored the antiviral activity of FT in the mosquito vector context. FT preserved its antiviral activity in the Aedes albopictus mosquito cell line and blocked the translocation of the DENV pre-membrane protein in a cell-free translation/translocation assay with insect microsomes. In an ex vivo DENV2 infected midgut model of Aedes aegypti mosquitoes FT preserved its antiviral activity, although in the micromolar range and with some related toxicity. In conclusion, this PhD project characterised the pan-DENV serotype and pan-orthoflaviviral potency of the CADA derivative FT. The antiviral activity of FT could be clearly attributed to selective inhibition of Sec61-directed translocation of the first N-terminal SP-like TMD of the viral polyprotein into the ER membrane. This confirms the critical role of the ER in orthoflavivirus replication and sets the base for selective Sec61 inhibitors as an alternative antiviral strategy against orthoflaviviruses.status: Publishe

    De effecten van een acute corticale beroerte op de subthalamische kern, motorische cortex en motorisch gedrag bij ratten

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    Stroke is the third leading cause of motor disability worldwide. Approximately 80% of patients with acute stroke experience upper limb motor impairments, and 50-60% of them continue to suffer long-term deficits. As a result, post-stroke motor recovery remains a major medical and societal challenge. Current therapies are often insufficient, largely due to an incomplete understanding of the neural mechanisms underlying motor disability and recovery. This study investigates the impact of acute cortical stroke (ACS) on neural activity in the subthalamic nucleus (STN) and examines the correlation between changes in STN activity and motor disability. Additionally, we assess whether ACS induces abnormal neural activity in the motor cortex and disrupts MC-STN coherence. These insights may inform the development of targeted interventions, especially the potential use of STN deep brain stimulation to improve motor outcomes after strokestatus: Publishe

    Inzichten in elektronengeleiding in op amorf indium-gallium-zinkoxide gebaseerde transistors

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    Amorphous metal oxide semiconductor like Indium-Gallium-Zinc-Oxide (IGZO) is the most commonly used oxide material in display application due to their field-effect mobility, good uniformity over large glass substrates sizes and low temperature process.Besides driving innovative thin-film transistors for display applications, IGZO is also seen as a strong candidate for replacing silicon in some architectures, helping the semiconductor industry to boost the scaling by placing the transistors in the Back-End-Of-Line of a chip rather than in the periphery. For example, thanks to its extremely low leakage current and its relatively good carrier mobility, IGZO TFT used as selector can make DRAM memories more power efficient while maintaining the data writing and reading at very high speed. In addition, channel material IGZO can be formed at a relatively low temperature, making it conducive for fabrication in stack array. Integration of such material in DRAM cell architecture opens up the possibility of 3D DRAM integration, which helps to continue the DRAM scaling roadmap. Our goal is to explore new schemes and improved material processing in order for IGZO devices to become practical in DRAM application.status: Publishe

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