IST Austria: PubRep (Institute of Science and Technology)
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Dual electronic and optical monitoring of biointerfaces by a grating-structured coplanar-gated field-effect transistor
No full textWe present a novel, portable sensor platform that enables concurrent monitoring of surface mass and charge density variations at thin biointerfaces. This platform combines a coplanar-gated field-effect transistor (FET) architecture with grating-coupled surface plasmon resonance (SPR), yielding an integrated disposable sensor chip prepared by nanoimprint and maskless photolithography techniques. The sensor chip design is suitable for scalable production and relies on reduced graphene oxide (rGO), serving as the FET’s semiconductor material for the electronic readout, and a metallic gate electrode surface that is corrugated with a multi-diffractive structure for optical probing with resonantly excited surface plasmons. Together with its integration in a compact instrumentation this results in a form factor optimized solution for dual-mode investigations without compromising the optical or electronic sensor performance. A poly-L-lysine (PLL) – based thin linker layer was deployed at the sensor surface to covalently attach azide-conjugated biomolecules by using incorporated “clickable” dibenzocyclooctyne (DBCO) moieties. Interestingly, the dual-mode measurements allow elucidating the role of the globular nature of the PLL chains when increasing the density of DBCO attached to their backbone, leading to PLL folding and internalization of DBCO moieties, and thus reducing the coupling yield for the used DNA oligomers. We envision that this platform can be employed to studying a range of other biointerface architectures and biomolecular interaction phenomena, which are inherently tied to mass and charge density variations
Tracy-Widom limit for free sum of random matrices
No full textWe consider fluctuations of the largest eigenvalues of the random matrix model A + UBU∗ where A and B are N × N deterministic Hermitian (or symmetric) matrices and U is a Haar-distributed unitary (or orthogonal) matrix. We prove that the largest eigenvalue weakly converges to the GUE (or GOE) Tracy–Widom distribution, under mild assumptions on A and B to
guarantee that the density of states of the model decays as square root around
the upper edge. Our proof is based on the comparison of the Green function
along the Dyson Brownian motion starting from the matrix A + UBU∗ and
ending at time N−1/3+o(1). As a byproduct of our proof, we also prove an
optimal local law for the Dyson Brownian motion up to the constant time
scale
On heroes in digraphs with forbidden induced forests
No full textWe continue a line of research which studies which hereditary families of digraphs have bounded dichromatic number. For a class of digraphs C, a hero in C is any digraph H
such that H -free digraphs in C have bounded dichromatic number. We show that if F
is an oriented star of degree at least five, the only heroes for the class of F -free digraphs are transitive tournaments. For oriented stars F of degree exactly four, we show the only heroes in F -free digraphs are transitive tournaments, or possibly special joins of transitive tournaments. Aboulker et al. characterized the set of heroes of {H,K1+P2→} -free digraphs almost completely, and we show the same characterization for the class of {H,rK1+P3→} -free digraphs. Lastly, we show that if we forbid two "valid" orientations of brooms, then every transitive tournament is a hero for this class of digraphs
Prethermalization for deformed Wigner matrices
No full textWe prove that a class of weakly perturbed Hamiltonians of the form H_λ= H_0 + λW, with W being a Wigner matrix, exhibits prethermalization. That is, the time evolution generated by H_λ relaxes to its ultimate thermal state via an intermediate prethermal state with a lifetime of order λ^{-2}. Moreover, we obtain a general relaxation formula, expressing the perturbed dynamics via the unperturbed dynamics and the ultimate thermal state. The proof relies on a two-resolvent law for the deformed Wigner matrix H_λ
Recessed microelectrodes as a platform to investigate the intrinsic redox process of Prussian blue analogs for energy storage application
No full textThe determination of the intrinsic properties of solid active material candidates is essential for their performance optimization. However, macroscopic electrodes and related analytical techniques show challenges concerning the number of additional influencing parameters. We explore recessed microelectrodes (rME) as a platform that allows for a binder-free investigation of Prussian Blue analogues (PBA), a family of promising battery materials. The enhanced diffusion using microelectrochemical tools is indispensable to assess the intrinsic material performance, overcoming the limitation of cation diffusion from the electrolyte to the solid interface during (dis)charging cycles and allowing the investigation of limiting steps in the coupled ion-electron transfer process. The intrinsic electrochemical performance of PBAs was studied in a three-electrode configuration by means of cyclic voltammetry and galvanostatic (dis)charging in aqueous Na+-containing electrolyte. We extended the evaluation to the role of the electrolyte on the performance of cathodic and anodic processes of a Mn-based PBA. Ex-situ and operando chemical characterization were coupled to support the microelectrochemical results
Linking molecular mechanisms to their evolutionary consequences: a primer
No full textA major obstacle to predictive understanding of evolution stems from the complexity of biological systems, which prevents detailed characterization of key evolutionary properties. Here, we highlight some of the major sources of complexity that arise when relating molecular mechanisms to their evolutionary consequences and ask whether accounting for every mechanistic detail is important to accurately predict evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial promoter regulated by 2 proteins, allowing us to connect any promoter genotype to 6 phenotypes that capture the dynamics of gene expression following an environmental switch. Accounting for the mechanisms that govern how this system works enabled us to provide an in-depth picture of how regulated bacterial promoters might evolve. More importantly, we used the model to explore which factors that contribute to the complexity of this system are essential for understanding its evolution, and which can be simplified without information loss. We found that several key evolutionary properties—the distribution of phenotypic and fitness effects of mutations, the evolutionary trajectories during selection for regulation—can be accurately captured without accounting for all, or even most, parameters of the system. Our findings point to the need for a mechanistic approach to studying evolution, as it enables tackling biological complexity and in doing so improves the ability to predict evolutionary outcomes
Information-flow interfaces
No full textContract-based design is a promising methodology for taming the complexity of developing sophisticated systems. A formal contract distinguishes between assumptions, which are constraints that the designer of a component puts on the environments in which the component can be used safely, and guarantees, which are promises that the designer asks from the team that implements the component. A theory of formal contracts can be formalized as an interface theory, which supports the composition and refinement of both assumptions and guarantees. Although there is a rich landscape of contract-based design methods that address functional and extra-functional properties, we present the first interface theory designed to ensure system-wide security properties. Our framework provides a refinement relation and a composition operation that support both incremental design and independent implementability. We develop our theory for both stateless and stateful interfaces. Additionally, we introduce information-flow contracts where assumptions and guarantees are sets of flow relations. We use these contracts to illustrate how to enrich information-flow interfaces with a semantic view. We illustrate the applicability of our framework with two examples inspired by the automotive domain
Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway
No full textIn the developing vertebrate central nervous system, neurons and glia typically arise
sequentially from common progenitors. Here, we report that the transcription factor Forkhead
Box G1 (Foxg1) regulates gliogenesis in the mouse neocortex via distinct cell-autonomous roles in progenitors and postmitotic neurons that regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate that loss of Foxg1 in cortical progenitors at neurogenic stages causes premature astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway component Fgfr3, which is suppressed by FOXG1 cell-autonomously to maintain neurogenesis. Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the augmentation of FGF signalling. We identify a second novel function of FOXG1 in regulating the expression of gliogenic cues in newborn neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons non-autonomously enhances gliogenesis in the progenitors via FGF signalling. These results fit well with the model that newborn neurons secrete cues that trigger progenitors to produce the next wave of cell types, astrocytes. If FGF signalling is attenuated in Foxg1 null progenitors, they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic signalling via the FGF pathway to regulate the sequential generation of neurons, astrocytes, and oligodendrocytes in the cerebral cortex
Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology
No full textVoltage-gated CaV2.1 (P/Q-type) Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to synaptic plasticity and to processes such as learning and memory. Despite their recognized importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact of AD pathology on the density and nanoscale compartmentalization of CaV2.1 channels in the hippocampus in association with GABAB receptors. Histoblotting experiments showed that the density of CaV2.1 channel was significantly reduced in the hippocampus of APP/PS1 mice in a laminar-dependent manner. CaV2.1 channel was enriched in the active zone of the axon terminals and was present at a very low density over the surface of dendritic tree of the CA1 pyramidal cells, as shown by quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL). In APP/PS1 mice, the density of CaV2.1 channel in the active zone was significantly reduced in the strata radiatum and lacunosum-moleculare, while it remained unaltered in the stratum oriens. The decline in Cav2.1 channel density was found to be associated with a corresponding impairment in the GABAergic synaptic function, as evidenced by electrophysiological experiments carried out in the hippocampus of APP/PS1 mice. Remarkably, double SDS-FRL showed a co-clustering of CaV2.1 channel and GABAB1 receptor in nanodomains (~40–50 nm) in wild type mice, while in APP/PS1 mice this nanoarchitecture was absent. Together, these findings suggest that the AD pathology-induced reduction in CaV2.1 channel density and CaV2.1-GABAB1 de-clustering may play a role in the synaptic transmission alterations shown in the AD hippocampus. Therefore, uncovering these layer-dependent changes in P/Q calcium currents associated with AD pathology can benefit the development of future strategies for AD management
Marcus kinetics control singlet and triplet oxygen evolving from superoxide
No full textOxygen redox chemistry is central to life1 and many human-made technologies, such as in energy storage2,3,4. The large energy gain from oxygen redox reactions is often connected with the occurrence of harmful reactive oxygen species3,5,6. Key species are superoxide and the highly reactive singlet oxygen3,4,5,6,7, which may evolve from superoxide. However, the factors determining the formation of singlet oxygen, rather than the relatively unreactive triplet oxygen, are unknown. Here we report that the release of triplet or singlet oxygen is governed by individual Marcus normal and inverted region behaviour. We found that as the driving force for the reaction increases, the initially dominant evolution of triplet oxygen slows down, and singlet oxygen evolution becomes predominant with higher maximum kinetics. This behaviour also applies to the widely observed superoxide disproportionation, in which one superoxide is oxidized by another, in both non-aqueous and aqueous systems, with Lewis and Brønsted acidity controlling the driving forces. Singlet oxygen yields governed by these conditions are relevant, for example, in batteries or cellular organelles in which superoxide forms. Our findings suggest ways to understand and control spin states and kinetics in oxygen redox chemistry, with implications for fields, including life sciences, pure chemistry and energy storage