Leiden University Scholary Publications
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Introduction: towards a long-term history of scholarly vices
Full text linkPolitics, Culture and National Identities 1789-presen
Unveiling the interplay of electronic and phononic excitations in laser-induced oxygen activation on Ru(0001)
No full textUnderstanding laser-induced dynamics on metal surfaces poses significant challenges due to the intricate interplay between electronic and phononic degrees of freedom, which evolve on distinct timescales. In this study, we introduce a machine learning-accelerated approach to molecular dynamics simulations that incorporates anisotropic electronic friction, providing deeper insights into these complex processes. Our framework extends the accessible time and length scales for nonadiabatic dynamics simulations, enabling a detailed investigation of the laser-induced activation of oxygen on the Ru(0001) surface. Statistical analysis reveals that strong electronic excitation dominates the first 800 fs after laser exposure. Beyond this timescale, energy deposited by electronic excitation continues to drive oxygen activation, while phonons, although always present as a dissipation channel, play a weaker role by buffering energy loss and redistributing kinetic energy among vibrational modes. The observed non-linear yield-fluence relationship, described by Y similar to Fn, underscores the pivotal role of electronic excitation. In addition, we identify the z-direction as the key activation mode for oxygen diffusion, with the exponent of the power law representing the quantized energy required for this process. This approach significantly accelerates dynamic simulations while offering valuable insights into the interplay between electronic and phononic excitations during laser-induced oxygen activation on Ru(0001).Theoretical Chemistr
Using muscle homing peptide CyPep10 to deliver phosphorodiamidate morpholino oligomers in the mdx mouse
Full text linkThe severe muscle wasting disorder Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin, a protein that is essential for muscle stability. Restoring this protein has therapeutic potential. Antisense oligonucleotides (ASOs), designed to target and skip exons, can restore the reading frame that is disrupted in these patients, enabling the production of partially functional dystrophin. Achieving optimal dystrophin restoration remains challenging due to limited delivery and cellular uptake. Muscle homing peptides conjugated to ASOs are a way to achieve this. Previously, CyPep10 (CP10) has been used to significantly increase exon skipping efficiency for the 2 '-O-methyl phosphorothioate chemistry in the mdx mouse model for DMD. Here, we explore the effect of using peptide CP10 as a conjugate to phosphorodiamidate morpholino oligomers (PMOs) ASOs to improve muscle delivery, thereby hoping to achieve increased treatment efficiency. Overall, we confirmed the homing ability of CP10 and observed significantly increased muscle tissue concentration levels of PMO when CP10 was conjugated. This did not lead to increased levels of exon skipping or dystrophin restoration. Conjugating both a cell-penetrating peptide (CPP) and CP10 to a PMO showed that increased exon skipping efficiency can be achieved to a slightly greater extent than with CPP-PMO treatment.Functional Genomics of Muscle, Nerve and Brain Disorder
Juridische en psychosociale hulpverlening aan slachtoffers van partnergeweld: een overzicht van het landschap op basis van slachtofferervaringen
Full text linkCriminal Justice: Maatschappelijk effectieve strafrechtspleging 2023-202
Alternating hemiplegia of childhood associated mutations in Atp1a3 reveal diverse neurological alterations in mice
Full text linkPathogenic variants in the neuronal Na+/K+ ATPase transmembrane ion transporter (ATP1A3) cause a spectrum of neurological disorders including alternating hemiplegia of childhood (AHC). The most common de novo pathogenic variants in AHC are p.D801N (similar to 40 % of patients) and p.E815K (similar to 25 % of patients), which lead to early mortality by spontaneous death in mice. Nevertheless, knowledge of the development of clinically relevant neurological phenotypes without the obstacle of premature death, is critical for the identification of pathophysiological mechanisms and ultimately, for the testing of therapeutic strategies in disease models. Here, we used hybrid vigor attempting to mitigate the fragility of AHC mice and then performed behavioral, electrophysiological, biochemical, and molecular testing to comparatively analyze mice that carry either of the two most common AHC patient observed variants in the Atp1a3 gene. Collectively, our data reveal the presence but also the differential impact of the p.D801N and p.E815K variants on disease relevant alterations such as spontaneous and stress-induced paroxysmal episodes, motor function, behavioral and neurophysiological activity, and neuroinflammation. Our alternate AHC mouse models with their phenotypic deficits open novel avenues for the investigation of disease biology and therapeutic testing for ATP1A3 research.Functional Genomics of Muscle, Nerve and Brain Disorder
‘Are they just putting up with me’? How diversity approaches impact LGBTQ+ employees' sense of being tolerated at work
Full text linkSocial decision makin
Connecting Cyprus: interregional interaction and society in the third millennium BC
Full text linkHow and why communities on Cyprus connected with the broader eastern Mediterranean in the third millennium BC has been much debated. In particular, the nature of the so-called Philia horizon, with its clear afnities with Anatolian assemblages, has been the topic of widely divergent perspectives on what happened and what role people on the island played. Using a constructed boundary perspective, I will reconsider the manner in which communities on Cyprus connected to adjacent lands in the third millennium BC during the Late Chalcolithic (2900–2500 BC) and the Philia (2500–2200 BC) periods. The aim is to demonstrate the selective nature of Anatolian assemblages and practices taken up in Cyprus in these periods, and how they are appropriated in local cultural practices that diverge considerably from those known on the mainland. This perspective leads to a marked shift in our ability to understand how Cyprus became increasingly connected to the broader eastern Mediterranean in the third millennium BC.World Archaeolog
