mTORC2 critically regulates renal potassium handling

The mTOR pathway orchestrates cellular homeostasis. The rapamycin-sensitive mTOR complex (mTORC1) in the kidney has been widely studied; however, mTORC2 function in renal tubules is poorly characterized. Here, we generated mice lacking mTORC2 in the distal tubule (Rictorfl/fl Ksp-Cre mice), which were viable and had no obvious phenotype, except for a 2.5-fold increase in plasma aldosterone. Challenged with a low-Na+ diet, these mice adequately reduced Na+ excretion; however, Rictorfl/fl Ksp-Cre mice rapidly developed hyperkalemia on a high-K+ diet, despite a 10-fold increase in serum aldosterone levels, implying that mTORC2 regulates kaliuresis. Phosphorylation of serum- and glucocorticoid-inducible kinase 1 (SGK1) and PKC-α was absent in Rictorfl/fl Ksp-Cre mice, indicating a functional block in K+ secretion activation via ROMK channels. Indeed, patch-clamp experiments on split-open tubular segments from the transition zone of the late connecting tubule and early cortical collecting duct demonstrated that Ba2+-sensitive apical K+ currents were barely detectable in the majority of Rictorfl/fl Ksp-Cre mice. Conversely, epithelial sodium channel (ENaC) activity was largely preserved, suggesting that the reduced ability to maintain K+ homeostasis is the result of impaired apical K+ conductance and not a reduced electrical driving force for K+ secretion. Thus, these data unravel a vital and nonredundant role of mTORC2 for distal tubular K+ handling

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

Social capital of venture capitalists and start-up funding

How does the social capital of venture capitalists (VCs) affect the funding of start-ups? By building on the rich social capital literature, we hypothesize a positive effect of VCs' social capital, derived from past syndication, on the amount of money that start-ups receive. Specifically, we argue that both structural and relational aspects of VCs' social networks provide VCs with superior access to information about current investment objects and opportunities to leverage them in the future, increasing their willingness to invest in these firms. Our empirical results, derived from a novel dataset containing more than 1,500 first funding rounds in the Internet and IT sector, strongly confirm our hypotheses. We discuss the implications of our findings for theories of venture capital and entrepreneurship, showing that the role and effect of VCs' social capital on start-up firms may be more complex than previously argued in the literature

Nontunneling high-order harmonics from ultra-intense laser-driven tightly bound systems

High-order harmonic emission is investigated by numerical solution of the weakly relativistic, two-dimensional Schrödinger equation for the case of ultra-intense laser-driven tightly bound systems (for example, multiply charged ions such as O7+ exposed to laser fields of the order of 1018 W cm-2 at 248 nm). In contrast to their usual substantial decrease, the low-order harmonics having an energy less than the ionization potential exhibit a high efficiency (i.e. intense) plateau with a well defined cutoff. The shape of this plateau is found to depend on the shape of the binding potential. A classical “surfing” mechanism for the generation of these harmonics is proposed that does not involve tunneling and that nevertheless explains the observed cutoff. Thus we call them “nontunneling harmonics.” The significance of relativistic effects for these harmonics is investigated and found to be small, despite the high laser intensity, because of the absence of tunneling

Interference in strong-field ionization of a two-centre atomic system

Strong-field photoionization of argon dimers by a few-cycle laser pulse is investigated using electron-ion coincidence momentum spectroscopy. The momentum distribution of the photoelectrons exhibits interference due to the emission from the two atomic argon centres, in analogy with a Young's doubleslit experiment. However, a simulation of the dimer photoelectron momentum spectrum based on the atomic spectrum supplemented with a theoretically derived interference term leads to distinct deviations from the experimental result. The deviations may have their origin in a complex electron dynamics during strong-field ionization of the Ar2 dimer. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft

Laser Induced Non-Sequential Double Ionization Investigated at and Below the Threshold for Electron Impact Ionization

We use correlated electron–ion momentum measurements to investigate laserinduced non-sequential double ionization of Ar and Ne. Light intensities are chosen in a regime at and below the threshold where, within the rescattering model, electron impact ionization of the singly charged ion core is expected to become energetically forbidden. Yet we find Ar2+ ion momentum distributions and an electron–electron momentum correlation indicative of direct impactionization. Within the quasistatic model this may be understood by assuming that the electric field of the light wave reduces the ionization potential of the singly charged ion core at the instant of scattering. The width of the projection of the ion momentum distribution onto an axis perpendicular to the light beam polarization vector is found to scalewiththe square root of the peak electric field strength in the light pulse. A scaling like this is not expected from the phase space available after electron impact ionization. It may indicate that the electric field at the instant of scattering is usually different fromzero and determines the transverse momentum distribution. A comparison of our experimental results with several theoretical results is give

The main concerns of European anaesthesiology postgraduate trainees: A European survey

This is the first study intended to identify the European anaesthesiology trainees' main concerns, to initiate a process of improvement of the training in anaesthesiology by the European Society of Anaesthesiology (ESA). The authors developed an electronic survey which addressed seven different concerns: autonomy transition, technical skills, exchange programs, residency costs, residency workload, employment prospects and educational contents/preparation for the European Diploma in Anaesthesiology and Intensive Care (EDAIC). The survey was disseminated by email to all anaesthesiology trainees registered in ESA and all European National Societies were asked to distribute the survey to their graduating trainees. 665 trainees initiated the survey with a completion rate of 54.6%. The trainees' main concerns were in descending order: educational contents, residency costs, employment prospects, residency workload, exchange programs, technical skills and autonomy transition. This report analyzes the three main concerns in more detail. 68% of respondents were unaware of the existence of the ESA e-learning platform. Other means to improve the preparation for the EDAIC such as a multiple-choice questions book should be developed. The main reason for not becoming an ESA Trainee member was the associated cost and 68% of respondents gave up activities or opportunities during their residency due to economic constraints; 56% of respondents considered emigrating for economic reasons and 28% elected Northern/Central Europe. The results of the present survey may provide additional background information for the development of specific improvements in strategies for training in anaesthesiology. (c) 2018 Elsevier Ltd. All rights reserved

P2Y2R Signaling Is Involved in the Onset of Glomerulonephritis

Endogenously released adenosine-5’-triphosphate (ATP) is a key regulator of physiological function and inflammatory responses in the kidney. Genetic or pharmacological inhibition of purinergic receptors has been linked to attenuation of inflammatory disorders and hence constitutes promising new avenues for halting and reverting inflammatory renal diseases. However, the involvement of purinergic receptors in glomerulonephritis (GN) has only been incompletely mapped. Here, we demonstrate that induction of GN in an experimental antibody-mediated GN model results in a significant increase of urinary ATP-levels and an upregulation of P2Y2R expression in resident kidney cells as well as infiltrating leukocytes pointing toward a possible role of the ATP/P2Y2R-axis in glomerular disease initiation. In agreement, decreasing extracellular ATP-levels or inhibition of P2R during induction of antibody-mediated GN leads to a reduction in all cardinal features of GN such as proteinuria, glomerulosclerosis, and renal failure. The specific involvement of P2Y2R could be further substantiated by demonstrating the protective effect of the lack of P2Y2R in antibody-mediated GN. To systematically differentiate between the function of P2Y2R on resident renal cells versus infiltrating leukocytes, we performed bone marrow-chimera experiments revealing that P2Y2R on hematopoietic cells is the main driver of the ATP/P2Y2R-mediated disease progression in antibody-mediated GN. Thus, these data unravel an important pro-inflammatory role for P2Y2R in the pathogenesis of GN

Separation of Recollision Mechanisms in Nonsequential Strong Field Double Ionization of Ar: The Role of Excitation Tunneling

Vector momentum distributions of two electrons created in double ionization of Ar by 25 fs, 0.25PW/cm2 laser pulses at 795 nm have been measured using a “reaction microscope.” At this intensity, where nonsequential ionization dominates, distinct correlation patterns are observed in the two-electron momentum distributions. A kinematical analysis of these spectra within the classical “recollision model” revealed an (e,2e)-like process and excitation with subsequent tunneling of the second electron as two different ionization mechanisms. This allows a qualitative separation of the two mechanisms demonstrating that excitation-tunneling is the dominant contribution to the total double ionization yield

Non-Sequential Double Ionization of Ne in Intense Laser Pulses: A Coincidence Experiment

The dynamics of Neon double ionization by 25 fs, 1.0 PW/cm2 laser pulses at 795 nm has been studied in a many particle coincidence experiment. The momentum vectors of all ejected atomic fragments (electrons and ions) have been measured using combined electron and recoil-ion momentum spectroscopy. Electron emission spectra for double and single ionization will be discussed. In both processes the mean electron energies differ considerably and high energetic electrons with energies of more than 120 eV have been observed for double ionization. The experimental results are in qualitative agreement with the rescattering model