Using small-angle scattering to guide functional magnetic nanoparticle design

in Nanoscale Advances (2022), 4

Association of ultra-rare coding variants with genetic generalized epilepsy: A case–control whole exome sequencing study

in Epilepsia (2022)

Abstract Objective We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set ... [more ▼]

Abstract Objective We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods We performed a case–control whole exome sequencing study in unrelated individuals of European descent diagnosed with GGE (previously recruited and sequenced through multiple international collaborations) and ancestry-matched controls. The association of ultra-rare variants (URVs; in 18 834 protein-coding genes) with epilepsy was examined in 1928 individuals with GGE (vs. 8578 controls), then separately in 945 individuals with familial GGE (vs. 8626 controls), and finally in 1005 individuals with sporadic GGE (vs. 8621 controls). We additionally examined the association of URVs with familial and sporadic GGE in two gene sets important for inhibitory signaling (19 genes encoding γ-aminobutyric acid type A [GABAA] receptors, 113 genes representing the GABAergic pathway). Results GABRG2 was associated with GGE (p = 1.8 × 10−5), approaching study-wide significance in familial GGE (p = 3.0 × 10−6), whereas no gene approached a significant association with sporadic GGE. Deleterious URVs in the most intolerant subgenic regions in genes encoding GABAA receptors were associated with familial GGE (odds ratio [OR] = 3.9, 95 confidence interval [CI] = 1.9–7.8, false discovery rate [FDR]-adjusted p = .0024), whereas their association with sporadic GGE had marginally lower odds (OR = 3.1, 95 CI = 1.3–6.7, FDR-adjusted p = .022). URVs in GABAergic pathway genes were associated with familial GGE (OR = 1.8, 95 CI = 1.3–2.5, FDR-adjusted p = .0024) but not with sporadic GGE (OR = 1.3, 95 CI = .9–1.9, FDR-adjusted p = .19). Significance URVs in GABRG2 are likely an important risk factor for familial GGE. The association of gene sets of GABAergic signaling with familial GGE is more prominent than with sporadic GGE. [less ▲]

Focal adhesion kinase plays a dual role in TRAIL resistance and metastatic outgrowth of malignant melanoma

in Cell Death and Disease (2022)

Despite remarkable advances in therapeutic interventions, malignant melanoma (MM) remains a life-threating disease. Following high initial response rates to targeted kinase-inhibition metastases quickly ... [more ▼]

Despite remarkable advances in therapeutic interventions, malignant melanoma (MM) remains a life-threating disease. Following high initial response rates to targeted kinase-inhibition metastases quickly acquire resistance and present with enhanced tumor progression and invasion, demanding alternative treatment options. We show 2nd generation hexameric TRAIL-receptor-agonist IZI1551 (IZI) to effectively induce apoptosis in MM cells irrespective of the intrinsic BRAF/NRAS mutation status. Conditioning to the EC50 dose of IZI converted the phenotype of IZI-sensitive parental MM cells into a fast proliferating and invasive, IZI-resistant metastasis. Mechanistically, we identified focal adhesion kinase (FAK) to play a dual role in phenotype-switching. In the cytosol, activated FAK triggers survival pathways in a PI3K- and MAPK-dependent manner. In the nucleus, the FERM domain of FAK prevents activation of wtp53, as being expressed in the majority of MM, and consequently intrinsic apoptosis. Caspase-8-mediated cleavage of FAK as well as FAK knockdown, and pharmacological inhibition, respectively, reverted the metastatic phenotype-switch and restored IZI responsiveness. FAK inhibition also re-sensitized MM cells isolated from patient metastasis that had relapsed from targeted kinase inhibition to cell death, irrespective of the intrinsic BRAF/NRAS mutation status. Hence, FAK-inhibition alone or in combination with 2nd generation TRAIL-receptor agonists may be recommended for treatment of initially resistant and relapsed MM, respectively. [less ▲]

Intersectional Inequalities in Science

in Proceedings of the National Academy of Sciences of the United States of America (2022), 119(2), 2113067119

The US scientific workforce is primarily composed of White men. Studies have demonstrated the systemic barriers preventing women and other minoritized populations from gaining entry to science; few ... [more ▼]

The US scientific workforce is primarily composed of White men. Studies have demonstrated the systemic barriers preventing women and other minoritized populations from gaining entry to science; few, however, have taken an intersectional perspective and examined the consequences of these inequalities on scientific knowledge. We provide a large-scale bibliometric analysis of the relationship between intersectional identities, topics, and scientific impact. We find homophily between identities and topic, suggesting a relationship between diversity in the scientific workforce and expansion of the knowledge base. However, topic selection comes at a cost to minoritized individuals for whom we observe both between- and within-topic citation disadvantages. To enhance the robustness of science, research organizations should provide adequate resources to historically underfunded research areas while simultaneously providing access for minoritized individuals into high-prestige networks and topics. [less ▲]

Dairy Intake and Parkinson's Disease: A Mendelian Randomization Study

in Movement Disorders (2022)

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained ... [more ▼]

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). Methods We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95 confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P-difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society [less ▲]

DYT6 mutated THAP1 is a cell type dependent regulator of the SP1 family.

in Brain : a journal of neurology (2022), 145(11), 3968-3984

DYT6 dystonia is caused by mutations in the transcription factor THAP1. THAP1 knock-out or knock-in mouse models revealed complex gene expression changes, which are potentially responsible for the ... [more ▼]

DYT6 dystonia is caused by mutations in the transcription factor THAP1. THAP1 knock-out or knock-in mouse models revealed complex gene expression changes, which are potentially responsible for the pathogenesis of DYT6 dystonia. However, how THAP1 mutations lead to these gene expression alterations and whether the gene expression changes are also reflected in the brain of THAP1 patients are still unclear. In this study we used epigenetic and transcriptomic approaches combined with multiple model systems [THAP1 patients' frontal cortex, THAP1 patients' induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic neurons, THAP1 heterozygous knock-out rat model, and THAP1 heterozygous knock-out SH-SY5Y cell lines] to uncover a novel function of THAP1 and the potential pathogenesis of DYT6 dystonia. We observed that THAP1 targeted only a minority of differentially expressed genes caused by its mutation. THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell type dependent manner. Comparing global differentially expressed genes detected in THAP1 patients' iPSC-derived midbrain dopaminergic neurons and THAP1 heterozygous knock-out rat striatum, we observed many common dysregulated genes and 61 of them were involved in dystonic syndrome-related pathways, like synaptic transmission, nervous system development, and locomotor behaviour. Further behavioural and electrophysiological studies confirmed the involvement of these pathways in THAP1 knock-out rats. Taken together, our study characterized the function of THAP1 and contributes to the understanding of the pathogenesis of primary dystonia in humans and rats. As SP1 family members were dysregulated in some neurodegenerative diseases, our data may link THAP1 dystonia to multiple neurological diseases and may thus provide common treatment targets. [less ▲]

Calibration of the Latest Generation Superconducting Gravimeter iGrav-043 Using the Observatory Superconducting Gravimeter OSG-CT040 and the Comparisons of Their Characteristics at the Walferdange Underground Laboratory for Geodynamics, Luxembourg

in Pure and Applied Geophysics (2022)

In December 2019, the latest generation transportable superconducting gravimeter (SG) iGrav-043 purchased by the University of Bonn was installed in the Walferdange Underground Laboratory for Geodynamics ... [more ▼]

In December 2019, the latest generation transportable superconducting gravimeter (SG) iGrav-043 purchased by the University of Bonn was installed in the Walferdange Underground Laboratory for Geodynamics (WULG) in the Grand Duchy of Luxembourg. In this paper, we estimate the calibration factor of the iGrav-043, which is essential for long-term gravity monitoring. We used simultaneously collected gravity data from the un-calibrated iGrav-043 and the calibrated Observatory superconducting gravimeter OSG-CT040 that operates continuously at WULG since 2002. The tidal analysis provides a simple way to transfer the calibration factor of one SG to the other. We then assess and compare tidal analyses, instrumental drifts and high frequency noises. After 20 years of continuous operation, the instrumental drift of the OSG-CT040 is almost zero. From 533 days of joint operation, we found that the instrumental drift of iGrav-043 exhibits a composite behavior: just after the setup and for two months a fast exponential decrease of 171 nm s−2, then a linear with a rate of 66 nm s−2 ± 10 nm s−2 per year. We suggest that a period of 3 months is sufficient for calibrating the iGrav. Accidental electrical power cuts triggered slight differences in the reaction and recovery of the OSG-CT040 and iGrav-043. However, it has been found that the long-term linear behavior of the drift was not affected. [less ▲]

When less is more: Investigating factors influencing the distraction effect of virtual reality from pain

in Frontiers in Pain Research (2022), 2

MAGNETOHYDRODYNAMIC ENHANCED ENTRY SYSTEM FOR SPACE TRANSPORTATION (MEESST) AS A KEY BUILDING BLOCK FOR LOW-COST INTERPLANETARY MISSIONS

in Journal of the British Interplanetary Society (2022), 74(12), 448-453

Aside from the launch environment, atmospheric re-entry imposes one of the most demanding environments which a spacecraft can experience. The combination of high spacecraft velocity and the presence of ... [more ▼]

Aside from the launch environment, atmospheric re-entry imposes one of the most demanding environments which a spacecraft can experience. The combination of high spacecraft velocity and the presence of atmospheric particles leads to partially ionised gas forming around the vehicle, which significantly inhibits radio communications, and leads to the generation of high thermal loads on the spacecraft surface. Currently, the latter is solved using expensive, heavy, and often expendable thermal protection systems (TPS). The use of electromagnetic fields to exploit Magnetohydrodynamic (MHD) principles has long been considered as an attractive solution for this problem. By displacing the ionised gas away from the spacecraft, the thermal loads can be reduced, while also opening a magnetic window for radio waves, mitigating the blackout phenomenon. The application of this concept has to date not been possible due to the large magnetic fields required, which would necessitate the use of exceptionally massive and power-hungry copper coils. High Temperature Superconductors (HTS) have now reached industrial maturity. HTS coils can now offer the necessary low weight and compactness required for space applications. The MEESST consortium the has been awarded a grant from the EU Horizon 2020 programme for the development and demonstration of a novel HTS-based re-entry system based with its foundation on MHD principles. The project will first harmonize existing numerical codes, and then design, manufacture, and test a HTS magnet. The study shows that the use of MEESST technology can have a positive impact on the cost-effectiveness and available payload of interplanetary missions. [less ▲]

Plateformes de règlement de litiges décentralisées : vers "une justice plus juste" ?

in Dalloz IP/IT (2022), 1

Proposition de modification des directives OPCVM et AIFM : Délégation par un gestionnaire de fonds d’investissement

in Revue de Droit Bancaire et Financier (2022)

Consultation de la Commission européenne sur le Listing Act : propositions, parfois iconoclastes, pour encourager la cotation des PME

in Revue des Sociétés (2022), (1), 56

Critical Review of the ATAD Implementation: The Implementation of the ATAD in Luxembourg

in Intertax (2022), 50(1), 56-65

This article examines the implementation of the ATAD in Luxembourg. Specifically, it analyses all the additions and amendments that had to be made into Luxembourg law, due to the ATAD. It does so in an ... [more ▼]

This article examines the implementation of the ATAD in Luxembourg. Specifically, it analyses all the additions and amendments that had to be made into Luxembourg law, due to the ATAD. It does so in an analytical and critical manner by going through all ATAD anti-avoidance provisions and examining the way they were implemented into Luxembourg law and how they differentiate from the previous rules (if they existed at all). It also critically assesses whether these changes have given rise to any inconsistencies or remaining questions. [less ▲]

Leveraging stretching directions for stationkeeping in Earth-Moon halo orbits

in Advances in Space Research (2022), 69(1), 620-646

Near Rectilinear Halo Orbits (NRHOs) are stable or nearly stable orbits that are defined as part of the L1 and L2 halo orbit families in the circular restricted three-body problem. Within the Earth-Moon ... [more ▼]

Near Rectilinear Halo Orbits (NRHOs) are stable or nearly stable orbits that are defined as part of the L1 and L2 halo orbit families in the circular restricted three-body problem. Within the Earth-Moon regime, the L1 and L2 NRHOs are proposed as long horizon trajectories for cislunar exploration missions, including NASA’s upcoming Gateway mission. The spacecraft, however, incurs continuous deviations due to unmodeled forces and orbit determination errors in this dynamically sensitive region. The current investigation focuses on an impulsive stationkeeping technique to maintain the spacecraft near a virtual reference orbit despite these uncertainties. The flow dynamics in the region are utilized to identify appropriate maneuver and target locations. The investigation reflects the impact of various factors on maneuver cost and efficacy. For orbits where position and velocity states are particularly sensitive to epoch time, an additional feedback control strategy is applied for phasing constraints. [less ▲]

Proposition de modification des directives OPCVM et AIFM

in Banque et Droit (2022)

Introduction to Smart Cities in Transition: Challenges of Participation in Urban Environments

in International Journal of Human-Computer Interaction (2022)

Opinion Statement ECJ-TF 2/2021 on the ECJ Decision of 25 February 2021 in Société Générale (Case C-403/19) on the Calculation of the Maximum Amount of a Foreign Direct Tax Credit

in European Taxation (2022)

The Court’s decision in Société Générale reinforces established case law that EU law neither prohibits juridical double taxation nor does it impose an obligation on the residence Member State to prevent ... [more ▼]

The Court’s decision in Société Générale reinforces established case law that EU law neither prohibits juridical double taxation nor does it impose an obligation on the residence Member State to prevent the disadvantages that could arise from the exercise of competence thus attributed by the two Member States. The parallel existence of taxing jurisdiction, however, must be distinguished from the exercise of such jurisdiction by each Member State. While Member States are free to determine the connecting factors for the allocation of taxing jurisdiction in tax treaties, in exercising the “power of taxation, so allocated by bilateral conventions for the avoidance of double taxation, the Member States must comply with EU rules and, more particularly, observe the principle of equal treatment”. It is generally accepted in the Court’s case law that both the ordinary credit and exemption (including exemption with progression) methods are permissible to avoid double taxation. In Société Générale, this position was confirmed, specifically as regards the “maximum deduction” under the ordinary credit method in tax treaties, even though this treatment can result in a disadvantage for cross-border income as compared with domestic income. As the disadvantage in Société Générale was due to the difference between gross-basis taxation of dividends in the source Member States (Italy, the Netherlands and the United Kingdom) and net-basis taxation of those foreign-sourced dividends in the residence state (France), it remains to be seen whether or not future cases will bring clarity in light of the Seabrokers decision of the EFTA Court, which examined how expenses can be lawfully allocated to foreign income from the perspective of the residence Member State. [less ▲]

Normative Coherence for Development and Regionalism: Gender equality in ASEAN’s migration policies

in Development Policy Review (2022)

Motivation:The United Nations2030 Agenda recognizesregions as important actors in implementing the sustainable development agenda.At the same time, regions are often criticized for lackingeffective ... [more ▼]

Motivation:The United Nations2030 Agenda recognizesregions as important actors in implementing the sustainable development agenda.At the same time, regions are often criticized for lackingeffective implementation, especially in relation to gender equality.Purpose:This study examines whether the Association of Southeast Asian Nations (ASEAN) implements its global commitment to gender equality at a regional level. Methods and approach:We apply qualitative analysis of key ASEAN documents in order to determinehow gender equality is implemented regionally. We particularly focus onframeworks related to female migrant workers in ASEAN. Findings: The analysis shows that ASEAN is formally committed to improving gender equality at a regional level, however, female migrants often end up in unfavourable conditions and precarious work relationships without any institutionalized protection because ASEAN's gender equality initiatives are largely concentrated in the Cultural Community and absent from the Economic Community, indicating an absence of normative coherence for developmentwith regard to gender equality. Policy implications:This limited impact of emerging regional commitments to gender equality arises from incoherencies in ASEAN’s normative governance. [less ▲]

Proposition de modification des directives OPCVM et AIFM : Dépositaires

in Revue de Droit Bancaire et Financier (2022)

Representaciones (ficticias) de un pequeño medio literario: el caso de la literatura luxemburguesa

in Theory Now (2022), 5(1), 77-96

Proposition de modification des directives OPCVM et AIFM : Qualité des dirigeants et moyens humains des gestionnaires de fonds d’investissement

in Revue de Droit Bancaire et Financier (2022)

Chronique de droit des marchés financiers

in Revue des Sociétés (2022)

From hybrid polariton to dipolariton using non-Hermitian Hamiltonians to handle particle lifetimes

in Physical Review. B, Condensed Matter (2022)

We consider photons strongly coupled to the excitonic excitations of a coupled quantum well, in the presence of an electric field. We show how, under a field increase, the hybrid polariton made of a ... [more ▼]

We consider photons strongly coupled to the excitonic excitations of a coupled quantum well, in the presence of an electric field. We show how, under a field increase, the hybrid polariton made of a photon coupled to hybrid carriers lying in the two wells transforms into a dipolariton made of a photon coupled to direct and indirect excitons. We also show how the cavity photon lifetime and the coherence time of the carrier wave vectors that we analytically handle through non-hermitian Hamiltonians affect these polaritonic states. While the hybrid polaritons display a spectral singularity where the eigenvalues coalesce, known as an exceptional point, that depends on detuning and lifetimes, we find that the three dipolaritonic states display an anticrossing without exceptional point due to the interaction between photons, direct, and indirect excitons. [less ▲]

Exploiting plasmonic enhancement with light-emitting diode excitation in surface-enhanced Raman scattering

in Journal of Raman Spectroscopy (2022), (April), 1--6

Surface-enhanced Raman scattering (SERS) is a well-established technique that enables the detection of very low molecular concentrations down to single molecules. Typical applications of SERS are the ... [more ▼]

Surface-enhanced Raman scattering (SERS) is a well-established technique that enables the detection of very low molecular concentrations down to single molecules. Typical applications of SERS are the consistent identification of various samples used in chemistry, biology, and physics among others. In contrast to common SERS setups, where lasers are used as excitation source, we exploit SERS to perform Raman spectroscopy with a light-emitting diode (LED). We demonstrate the applicability of our approach on four different Raman reporters. We unambiguously distinguish two similar designer molecules 4-nitrothiophenol (p-NTP) and 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) that are often used in SERS experiments. Additionally, we probe Rhodamine 6G that is used in many different applications and carbon nanotubes as a one-dimensional solid state nanosystem. The LED excited surface-enhanced Raman spectra reproduce the characteristic Raman modes of the different samples. We compare the LED spectra to Raman spectra excited with a laser at the same wavelength. We envision the combination of LED sources with SERS substrates in the next generation of handheld devices and low-cost Raman setups. [less ▲]

Rez.: Rolf G. Renner, "Peter Handke. Erzählwelten – Bilderordnungen"

in Zeitschrift für Germanistik (2022), 32(1), 239-241

Maxwell Demon that Can Work at Macroscopic Scales

in Physical Review Letters (2022), 129(12), 120602

Assessing the Performance of Gradient-Boosting Models for Predicting the Travel Mode Choice Using Household Survey Data

in Journal of Urban Planning and Development (2022), 148(2), 04022007

Nanomechanical Spectroscopy of 2D Materials

in Nano Letters (2022), 22(20), 8037--8044

We introduce a nanomechanical platform for fast and sensitive measurements of the spectrally resolved optical dielectric function of 2D materials. At the heart of our approach is a suspended 2D material ... [more ▼]

We introduce a nanomechanical platform for fast and sensitive measurements of the spectrally resolved optical dielectric function of 2D materials. At the heart of our approach is a suspended 2D material integrated into a high Q silicon nitride nanomechanical resonator illuminated by a wavelength-tunable laser source. From the heating-related frequency shift of the resonator as well as its optical reflection measured as a function of photon energy, we obtain the real and imaginary parts of the dielectric function. Our measurements are unaffected by substrate-related screening and do not require any assumptions on the underling optical constants. This fast ($\tau$rise∼135 ns), sensitive (noise-equivalent power = 90 pW/√Hz), and broadband (1.2-3.1 eV, extendable to UV-THz) method provides an attractive alternative to spectroscopic or ellipsometric characterization techniques. [less ▲]

Insights from an information thermodynamics analysis of a synthetic molecular motor

in Nature Chemistry (2022), 14(5), 530-537

Information is physical, a realization that has transformed the physics of measurement and communication. However, the flow between information, energy and mechanics in chemical systems remains largely ... [more ▼]

Information is physical, a realization that has transformed the physics of measurement and communication. However, the flow between information, energy and mechanics in chemical systems remains largely unexplored. Here we analyse a minimalist autonomous chemically driven molecular motor in terms of information thermodynamics, a framework that quantitatively relates information to other thermodynamic parameters. The treatment reveals how directional motion is generated by free energy transfer from chemical to mechanical (conformational and/or co-conformational) processes by `energy flow' and `information flow'. It provides a thermodynamic level of understanding of molecular motors that is general, complements previous analyses based on kinetics and has practical implications for machine design. In line with kinetic analysis, we find that power strokes do not affect the directionality of chemically driven machines. However, we find that power strokes can modulate motor velocity, the efficiency of free energy transfer and the number of fuel molecules consumed per cycle. This may help explain the role of such (co-)conformational changes in biomachines and illustrates the interplay between energy and information in chemical systems. [less ▲]

Reliability and entropy production in nonequilibrium electronic memories

in Physical Review. E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics (2022), 105(3), 034107

Imaging Erythrocyte Sedimentation in Whole Blood

in Frontiers in Physiology (2022), 12

The erythrocyte sedimentation rate (ESR) is one of the oldest medical diagnostic tools. However, currently there is some debate on the structure formed by the cells during the sedimentation process. While ... [more ▼]

The erythrocyte sedimentation rate (ESR) is one of the oldest medical diagnostic tools. However, currently there is some debate on the structure formed by the cells during the sedimentation process. While the conventional view is that erythrocytes sediment as separate aggregates, others have suggested that they form a percolating gel, similar to other colloidal suspensions. However, visualization of aggregated erythrocytes, which would settle the question, has always been challenging. Direct methods usually study erythrocytes in 2D situations or low hematocrit (∼1%). Indirect methods, such as scattering or electric measurements, provide insight on the suspension evolution, but cannot directly discriminate between open or percolating structures. Here, we achieved a direct probing of the structures formed by erythrocytes in blood at stasis. We focused on blood samples at rest with controlled hematocrit of 45%, from healthy donors, and report observations from three different optical imaging techniques: direct light transmission through thin samples, two-photon microscopy and light-sheet microscopy. The three techniques, used in geometries with thickness from 150 μm to 3 mm, highlight that erythrocytes form a continuous network with characteristic cracks, i.e., a colloidal gel. The characteristic distance between the main cracks is of the order of ∼100 μm. A complete description of the structure then requires a field of view of the order of ∼1 mm, in order to obtain a statistically relevant number of structural elements. A quantitative analysis of the erythrocyte related processes and interactions during the sedimentation need a further refinement of the experimental set-ups. [less ▲]

Le financement du plan de relance européen : audaces fortuna juvat

in Revue des Affaires Européennes (2022), 2022(2), 797-806

Exploration of whether socioeconomic factors affect the results of priority setting partnerships: updating the top 10 research priorities for the management of Parkinson's in an international setting.

in BMJ open (2022), 12(6), 049530

OBJECTIVES: Explore whether socioeconomic differences of patients affect the prioritisation of pre-existing research questions and explore the agreement between healthcare professionals (HCP) and patients ... [more ▼]

OBJECTIVES: Explore whether socioeconomic differences of patients affect the prioritisation of pre-existing research questions and explore the agreement between healthcare professionals (HCP) and patients in priority setting partnerships (PSPs). DESIGN AND SETTING: Prospective, three centre survey across UK (400 participants), Tuebingen (176 participants) and Luxembourg (303 participants). People with Parkinson's (PwP), research participants, relatives and HCP associated with three Parkinson's cohort studies were invited to participate, along with linked centres (clinical care settings, research groups, charities). Responders were encouraged to pass on the survey to friends/families/carers. METHODS: The survey involved rating the importance of research questions on a Likert scale, allowing for the generation of one new question participants felt was particularly important. Collection of demographic information allowed for comparisons of priorities across a range of socioeconomic variables; the top 10 research priorities for each group were then compared. Questions added by participants were subject to a thematic analysis. RESULTS: 879 participants completed the survey (58% PwP, 22% family/friends, 13% HCP, 4% carers). Finding the best form of physiotherapy for PwP was the number one priority across the majority of analyses. HCP were the only subgroup not to place physiotherapy in the top 10. Factors most likely to affect prioritisation in PwP included educational level, presence of carer support and disease duration. There was little difference between other socioeconomic categories. CONCLUSIONS: Socioeconomic factors modestly influenced some research priority ratings but did not significantly affect the top priority in most comparisons. Future studies must ensure patients from a range of socioeconomic backgrounds are recruited, ensuring results generalisable to the public while also identifying any key disparities in prioritisation. PSP should also take care that HCP do not skew results during prioritisation of questions, as in this study the most important priority to patients was not identified by professionals. [less ▲]

Exploring the soil: Not a sentimental journey

in OASE: Tijdschrift voor Architectuur (2022), (110), 4-15

Single-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson’s disease

in Communications Biology (2022), 5(1), 1--19

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly ... [more ▼]

Parkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson’s disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD. [less ▲]

FinTech and the Four Horsemen of the Apocalypse

in Banking and Finance Law Review (2022), 39

Executing trades in style: Retail investors vs. institutions.

in Asia-Pacific Journal of Accounting and Economics (2022), 29(2), 344-362

Continuous Percoll Gradient Centrifugation of Erythrocytes-Explanation of Cellular Bands and Compromised Age Separation

in CELLS (2022), 11(8),

(1) Background: When red blood cells are centrifuged in a continuous Percoll-based density gradient, they form discrete bands. While this is a popular approach for red blood cell age separation, the ... [more ▼]

(1) Background: When red blood cells are centrifuged in a continuous Percoll-based density gradient, they form discrete bands. While this is a popular approach for red blood cell age separation, the mechanisms involved in banding were unknown. (2) Methods: Percoll centrifugations of red blood cells were performed under various experimental conditions and the resulting distributions analyzed. The age of the red blood cells was measured by determining the protein band 4.1a to 4.1b ratio based on western blots. Red blood cell aggregates, so-called rouleaux, were monitored microscopically. A mathematical model for the centrifugation process was developed. (3) Results: The red blood cell band pattern is reproducible but re-centrifugation of sub-bands reveals a new set of bands. This is caused by red blood cell aggregation. Based on the aggregation, our mathematical model predicts the band formation. Suppression of red blood cell aggregation reduces the band formation. (4) Conclusions: The red blood cell band formation in continuous Percoll density gradients could be explained physically by red blood cell aggregate formation. This aggregate formation distorts the density-based red blood cell age separation. Suppressing aggregation by osmotic swelling has a more severe effect on compromising the RBC age separation to a higher degree. [less ▲]

Obstacles to demand response: Why industrial companies do not adapt their power consumption to volatile power generation

in Energy Policy (2022), 165

Various flexibility options in power systems, such as storage, grid expansion, and demand flexibility, gain increasing importance to balance the intermittent power supply of renewables. On the demand side ... [more ▼]

Various flexibility options in power systems, such as storage, grid expansion, and demand flexibility, gain increasing importance to balance the intermittent power supply of renewables. On the demand side, especially the industrial sector represents promising potential for Demand Response, i.e., the alignment of its power demand with the current power supply of renewables. However, there exist various obstacles that currently prevent companies from investing in new or (fully) exploiting existing flexibility potentials. In this paper, we investigate how economic, regulatory, technological, organizational, behavioral, informational, and competence obstacles pose barriers for companies to adjust their power consumption flexibly. For this purpose, we combine both a structured literature analysis and a case study. For the case study, we conduct 16 interviews with energy experts from companies from different industries. Our findings reveal that due to technical risk of disrupting the production process, lacking revenues, and too low cost savings, companies do not flexibilize their power consumption. Moreover, in particular, contradictory legislative incentives and missing IT standardization and interoperability represent key obstacles. Therefore, our results constitute a basis for targeted policy making in order to foster the exploitation of (existing) flexibility potential of industrial companies on the demand side. [less ▲]

The EU Sustainable Finance Framework in Light of International Standards

in Journal of International Economic Law (2022), 25(4), 659679

Voir ou être vu : analyses de visibilité depuis le site de Chèvremont (commune de Chaudfontaine, Belgique)

in Bulletin de la Société Géographique de Liège (2022), 1

Le site de Chèvremont est connu dans l’histoire liégeoise depuis le Haut Moyen-Âge. L’archéologie a montré que la colline a été fréquentée depuis au moins la période néolithique. Intuitivement, tous les ... [more ▼]

Le site de Chèvremont est connu dans l’histoire liégeoise depuis le Haut Moyen-Âge. L’archéologie a montré que la colline a été fréquentée depuis au moins la période néolithique. Intuitivement, tous les auteurs qui se sont rendus sur le site décrivent un endroit d’où le panorama est impressionnant. Nous tentons ici d’utiliser les analyses de visibilité pour mesurer et comparer l’ampleur de la visibilité atteinte depuis plusieurs points du plateau sommital. [less ▲]

Do financial performance indicators predict 10-K text sentiments? An application of artificial intelligence

in Research in International Business and Finance (2022), 61

n this study, we employ Natural Language Processing (NLP), a subdomain of artificial intelligence (AI), to predict the sentiments while analyzing 3729 annual 10-k financial reports of S&P 500 companies ... [more ▼]

n this study, we employ Natural Language Processing (NLP), a subdomain of artificial intelligence (AI), to predict the sentiments while analyzing 3729 annual 10-k financial reports of S&P 500 companies over the 2002–2019 time period. Our findings suggest that the firm’s financial performance indicators help reduce negativity in the textual part of 10-ks. In contrast, we do not observe any significant association between the firm’s financial performance indicators and 10-ks positivity. Our findings are robust to alternative econometric specifications and alternative measures of key variables. Our results contribute to the accounting and financial disclosure literature by indicating that corporate financial performance indicators can predict the tone of 10-k filings. [less ▲]

Channel Estimation for UAV Communication Systems Using Deep Neural Networks

in Drones (2022)

Channel modeling of unmanned aerial vehicles (UAVs) from wireless communications has gained great interest for rapid deployment in wireless communication. The UAV channel has its own distinctive ... [more ▼]

Channel modeling of unmanned aerial vehicles (UAVs) from wireless communications has gained great interest for rapid deployment in wireless communication. The UAV channel has its own distinctive characteristics compared to satellite and cellular networks. Many proposed techniques consider and formulate the channel modeling of UAVs as a classification problem, where the key is to extract the discriminative features of the UAV wireless signal. For this issue, we propose a framework of multiple Gaussian–Bernoulli restricted Boltzmann machines (GBRBM) for dimension reduction and pre-training utilization incorporated with an autoencoder-based deep neural network. The developed system used UAV measurements of a town’s already existing commercial cellular network for training and validation. To evaluate the proposed approach, we run ray-tracing simulations in the program Remcom Wireless InSite at a distinct frequency of 28 GHz and used them for training and validation. The results demonstrate that the proposed method is accurate in channel acquisition for various UAV flying scenarios and outperforms the conventional DNNs. [less ▲]

Deterministic control of ferroelectric polarization by ultrafast laser pulses

in Nature Communications (2022), 13

No Ensemble Averaging Below the Black Hole Threshold

in Journal of High Energy Physics (2022), 7

In the AdS/CFT correspondence, amplitudes associated to connected bulk manifolds with disconnected boundaries have presented a longstanding mystery. A possible interpretation is that they reflect the ... [more ▼]

In the AdS/CFT correspondence, amplitudes associated to connected bulk manifolds with disconnected boundaries have presented a longstanding mystery. A possible interpretation is that they reflect the effects of averaging over an ensemble of boundary theories. But in examples in dimension D≥3, an appropriate ensemble of boundary theories does not exist. Here we sharpen the puzzle by identifying a class of "sub-threshold" observables that we claim do not show effects of ensemble averaging. These are amplitudes that do not involve black hole states. To support our claim, we explore the example of D=3, and show that connected solutions of Einstein's equations with disconnected boundary never contribute to sub-threshold observables. To demonstrate this requires some novel results about the renormalized volume of a hyperbolic three-manifold, which we prove using modern methods in hyperbolic geometry. Why then do any observables show apparent ensemble averaging? We propose that this reflects the chaotic nature of black hole physics and the fact that the Hilbert space describing a black hole does not have a large N limit. [less ▲]

The rise of decentralized autonomous organizations (DAOs): a first empirical glimpse

in Venture Capital (2022)

Blockchain technology and smart contracts are catalysts for decentralization and disintermediation. These new technologies reduce transaction costs, agency costs, and offer a basis for trustless social ... [more ▼]

Blockchain technology and smart contracts are catalysts for decentralization and disintermediation. These new technologies reduce transaction costs, agency costs, and offer a basis for trustless social and economic interactions. They are fueling new business models for decentralized platforms and have revolutionized crowdfunding. A recent trend, Decentralized Autonomous Organizations (DAOs), stands to fundamentally transform organizing and governance. DAOs are blockchain-native, decentralized organizations that are collectively owned and managed by their members via smart contracts. In this note, we assess the promises and challenges of DAOs, with a focus on decentralized governance and disintermediation, and offer a first empirical glimpse at the rise and functioning of DAOs. Overall, DAOs may introduce a new era in organizational economics, transforming the global corporate landscape from hierarchical organizations to democratic and distributed organizations powered by organizational entrepreneurship and innovations. [less ▲]

An Evolving International Research Collaboration Network: Spatial and Thematic Developments in Co-Authored Higher Education Research, 1998–2018

in Scientometrics (2022), 127

Co-authored research articles in the disciplinarily heterogeneous field of higher education have dramatically increased in this century, largely driven, as in other fields, by rising international co ... [more ▼]

Co-authored research articles in the disciplinarily heterogeneous field of higher education have dramatically increased in this century, largely driven, as in other fields, by rising international co-authorships. We examine this evolving international collaboration network in higher education research over two decades. To do so, we apply automated bibliometric topic identification and social network analysis of 9,067 papers in 13 core higher education journals (1998–2018). Remarkable expansion in the volume of papers and co-authorships has, surprisingly, not resulted in a more diverse network. Rather, existing co-authorship patterns are strengthened, with the dominance of scholars from a few Anglophone countries largely maintained. Researchers globally seek to co-author with leading scholars in these countries, especially the US, UK, and Australia—at least when publishing in the leading general HE journals based there. Further, the two-mode social network analysis of countries and topics suggests that while Anglophone countries have led the development of higher education research, China and Germany, as leading research-producing countries, are increasingly influential within this world-spanning network. Topically, the vast majority of co-authored papers in higher education research focuses on individual-level phenomena, with organizational and system-level or country-level analysis constituting a (much) smaller proportion, despite policymakers’ emphasis on cross-national comparisons and the growing importance of university actorhood. We discuss implications thereof for the future of the multidisciplinary higher education field. [less ▲]

Dimensionality Reduction, Modelling, and Optimization of Multivariate Problems Based on Machine Learning

in Symmetry (2022), 14(7), 1282

Personalised meta-path generation for heterogeneous graph neural networks

in Data Mining and Knowledge Discovery (2022), 36(6), 2299-2333

In Vitro Erythropoiesis at Different pO(2) Induces Adaptations That Are Independent of Prior Systemic Exposure to Hypoxia

in CELLS (2022), 11(7),

Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a ... [more ▼]

Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation of the concept of neocytolysis. [less ▲]