Explore the vast range of titles available.

The glomerular filtration barrier (GFB) produces primary urine and is composed of a fenestrated endothelium, a glomerular basement membrane (GBM), podocytes, and a slit diaphragm. Impairment of the GFB leads to albuminuria and microhematuria. The GBM is generated via secreted proteins from both endothelial cells and podocytes and is supposed to majorly contribute to filtration selectivity. While genetic mutations or variations of GBM components have been recently proposed to be a common cause of glomerular diseases, pathways modifying and stabilizing the GBM remain incompletely understood. Here, we identified prolyl 3-hydroxylase 2 (P3H2) as a regulator of the GBM in an a cohort of patients with albuminuria. P3H2 hydroxylates the 3' of prolines in collagen IV subchains in the endoplasmic reticulum. Characterization of a P3h2ΔPod mouse line revealed that the absence of P3H2 protein in podocytes induced a thin basement membrane nephropathy (TBMN) phenotype with a thinner GBM than that in WT mice and the development of microhematuria and microalbuminuria over time. Mechanistically, differential quantitative proteomics of the GBM identified a significant decrease in the abundance of collagen IV subchains and their interaction partners in P3h2ΔPod mice. To our knowledge, P3H2 protein is the first identified GBM modifier, and loss or mutation of P3H2 causes TBMN and focal segmental glomerulosclerosis in mice and humans.

In this review, we will primarily focus on the role of members of the low-density lipoprotein receptor (LDL-R) family that are involved in trafficking and processing of the amyloid precursor protein (APP). We will discuss the role of the LDL-receptor family members, low-density lipoprotein receptor-related protein 1 (LRP1), LRP1b, apolipoprotein E receptor 2, sortilin-related receptor (SorLA/LR11) and megalin/LRP2 on the physiological function of APP and its cellular localization. Additionally, we will focus on adaptor proteins that have been shown to influence the physiological function of LDL-R family members in combination with APP processing. The results in this review emphasize that the physiological function of APP cannot be explained by the focus on the APP protein alone but rather in combination with various direct or indirect interaction partners within the cellular environment.

Majorana fermions, which are their own antiparticles, are expected to exist in topological superconductors. A study using superconducting leads in contact with a quantum well reveals the presence of supercurrents along one-dimensional sample edges of a quantum spin Hall state. These edge supercurrents are topological. Topological insulators are a newly discovered phase of matter characterized by gapped bulk states surrounded by conducting boundary states 1 , 2 , 3 . Since their theoretical discovery, these materials have encouraged intense efforts to study their properties and capabilities. Among the most striking results of this activity are proposals to engineer a new variety of superconductor at the surfaces of topological insulators 4 , 5 . These topological superconductors would be capable of supporting localized Majorana fermions, particles whose braiding properties have been proposed as the basis of a fault-tolerant quantum computer 6 . Despite the clear theoretical motivation, a conclusive realization of topological superconductivity remains an outstanding experimental goal. Here we present measurements of superconductivity induced in two-dimensional HgTe/HgCdTe quantum wells, a material that becomes a quantum spin Hall insulator when the well width exceeds d C  = 6.3 nm (ref.  7 ). In wells that are 7.5 nm wide, we find that supercurrents are confined to the one-dimensional sample edges as the bulk density is depleted. However, when the well width is decreased to 4.5 nm the edge supercurrents cannot be distinguished from those in the bulk. Our results provide evidence for supercurrents induced in the helical edges of the quantum spin Hall effect, establishing this system as a promising avenue towards topological superconductivity. In addition to directly confirming the existence of the topological edge channels, our results also provide a measurement of their widths, which range from 180 nm to 408 nm.

In stochastic resonance, the combination of a weak signal with noise leads to its amplification and optimization1. This phenomenon has been observed in several systems in contexts ranging from palaeoclimatology, biology, medicine, sociology and economics to physics1–9. In all these cases, the systems were either operating in the presence of thermal noise or were exposed to external classical noise sources. For quantum-mechanical systems, it has been theoretically predicted that intrinsic fluctuations lead to stochastic resonance as well, a phenomenon referred to as quantum stochastic resonance1,10,11, but this has not been reported experimentally so far. Here we demonstrate tunnelling-controlled quantum stochastic resonance in the a.c.-driven charging and discharging of single electrons on a quantum dot. By analysing the counting statistics12–16, we demonstrate that synchronization between the sequential tunnelling processes and a periodic driving signal passes through an optimum, irrespective of whether the external frequency or the internal tunnel coupling is tuned.Quantum stochastic resonance, in which the quantum fluctuation represents the noise needed to amplify an otherwise weak signal, is reported in the charging and discharging of a single-electron quantum dot.

The splitting of electron pairs, which is essential for electron-based quantum information processing, can now be obtained with electron pairs that have been generated on-demand. The on-demand generation and separation of entangled photon pairs are key components of quantum information processing in quantum optics 1 , 2 , 3 . In an electronic analogue, the decomposition of electron pairs represents an essential building block for using the quantum state of ballistic electrons in electron quantum optics 4 , 5 , 6 , 7 . The scattering of electrons has been used to probe the particle statistics of stochastic sources in Hanbury Brown and Twiss experiments 8 , 9 and the recent advent of on-demand sources further offers the possibility to achieve indistinguishability between multiple sources in Hong–Ou–Mandel experiments 10 , 11 , 12 , 13 , 14 , 15 . Cooper pairs impinging stochastically at a mesoscopic beamsplitter have been successfully partitioned, as verified by measuring the coincidence of arrival 16 , 17 , 18 , 19 , 20 , 21 . Here, we demonstrate the splitting of electron pairs generated on demand. Coincidence correlation measurements allow the reconstruction of the full counting statistics, revealing regimes of statistically independent, distinguishable or correlated partitioning, and have been envisioned as a source of information on the quantum state of the electron pair 22 , 23 , 24 , 25 , 26 . The high pair-splitting fidelity opens a path to future on-demand generation of spin-entangled electron pairs from a suitably prepared two-electron quantum-dot ground state.

Power Hardware-in-the-Loop (PHiL) simulation is an emerging testing methodology of real hardware equipment within an emulated virtual environment. The closed loop interfacing between the Hardware under Test (HuT) and the Real Time Simulation (RTS) enables a realistic simulation but can also result in an unstable system. In addition to fundamentals in PHiL simulation and interfacing, this paper therefore provides a consistent and comprehensive study of PHiL stability. An analytic analysis is compared with a simulative approach and is supplemented by practical validations of the stability limits in PHiL simulation. Special focus is given on the differences between a switching and a linear amplifier as power interface (PI). Stability limits and the respective factors of influence (e.g., Feedback Current Filtering) are elaborated with a minimal example circuit with voltage-type Ideal Transformer Model (ITM) PHiL interface algorithm (IA). Finally, the findings are transferred to a real low-voltage grid PHiL application with residential load and photovoltaic system.

Chronic kidney disease (CKD) is a major health-care burden. Increasing evidence suggests that a considerable proportion of patients are affected by a monogenic kidney disorder. In this study, the kidney transplantation waiting list at the Charité was screened for patients with undetermined cause of CKD. By next-generation sequencing (NGS) we targeted all 600 genes described and associated with kidney disease or allied disorders. In total, 635 patients were investigated. Of these, 245 individuals had a known cause of CKD (38.5%) of which 119 had a proven genetic disease (e.g., ADPKD, Alport). The other 340 patients (53.5%) were classified as undetermined diagnosis, of whom 87 had kidney failure (KF) onset <40 years. To this latter group genetic testing was offered as well as to those patients (n = 29) with focal segmental glomerulosclerosis (FSGS) and all individuals (n = 21) suspicious for thrombotic microangiopathy (TMA) in kidney biopsy. We detected diagnostic variants in 26 of 126 patients (20.6%) of which 14 of 126 (11.1%) were pathogenic or likely pathogenic. In another 12 of 126 (9.5%) patients, variants of unknown significance (VUS) were detected. Our study demonstrates the diagnostic value of comprehensive genetic testing among patients with undetermined CKD.

Shot noise can be suppressed, which is essential for improving the performance of quantum transport devices, by using an electronic closed-loop feedback that monitors and adjusts the counting statistics. Feedback control of quantum mechanical systems is rapidly attracting attention not only due to fundamental questions about quantum measurements 1 , but also because of its novel applications in many fields in physics. Quantum control has been studied intensively in quantum optics 1 , 2 but progress has recently been made in the control of solid-state qubits 3 , 4 , 5 as well. In quantum transport only a few active 6 , 7 , 8 and passive 9 , 10 , 11 feedback experiments have been realized on the level of single electrons, although theoretical proposals 12 , 13 , 14 exist. Here we demonstrate the suppression of shot noise in a single-electron transistor using an exclusively electronic closed-loop feedback to monitor and adjust the counting statistics 6 , 15 , 16 , 17 , 18 , 19 , 20 . With increasing feedback response we observe a stronger suppression and faster freezing of charge current fluctuations. Our technique is analogous to the generation of squeezed light with in-loop photodetection 1 , 21 , 22 as used in quantum optics. Sub-Poisson single-electron sources will pave the way for high-precision measurements in quantum transport similar to optical or optomechanical 23 equivalents.

The transition to inverter-dominated power systems with novel control strategies has created weak grid scenarios, prompting extensive research into grid-forming (GFM) converters and advanced GFM control schemes. This study evaluates two GFM control strategies for their stabilizing effects in weakly interconnected and islanded power systems: the established Virtual Synchronous Machine (VSM) control and the newly developed Phase-Restoring Principle (PRP). The evaluation is conducted using a real-time electromagnetic transient (EMT) simulation testbed with Hardware-in-the-Loop (HiL) capabilities. The system includes a multi-terminal medium-voltage (MVDC) and high-voltage direct current (HVDC) network weakly coupled to a network equivalent, represented by a scaled synchronous machine (SynM) to replicate grid inertia. Modular multilevel converters (MMCs) model the converters, while Power Hardware-in-the-Loop (PHiL) experiments integrate real power hardware. Dynamic interactions, including islanded conditions, are emulated to assess the performance of GFM controls and their interactions in HV/MV and AC/DC systems. The results demonstrate the compatibility of diverse GFM schemes with grid-following controls and synchronous machines, emphasizing their positive contributions to system stability. This modular demonstrator, as a realistic prototype of future power systems, provides a flexible platform for testing emerging GFM strategies and hardware, supporting the development of robust and stable inverter-based grids.

BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).