Tuneable defect-curvature coupling and topological transitions in active shells.

Recent experimental observations have suggested that topological defects can facilitate the creation of sharp features in developing embryos. Whereas these observations echo established knowledge about the interplay between geometry and topology in two-dimensional passive liquid crystals, the role of activity has mostly remained unexplored. In this article we focus on deformable shells consisting of either polar or nematic active liquid crystals and demonstrate that activity renders the mechanical coupling between defects and curvature much more involved and versatile than previously thought. Using a combination of linear stability analysis and three-dimensional computational fluid dynamics, we demonstrate that such a coupling can in fact be tuned, depending on the type of liquid crystal order, the specific structure of the defect (i.e. asters or vortices) and the nature of the active forces. In polar systems, this can drive a spectacular transition from spherical to toroidal topology, in the presence of large extensile activity. Our analysis strengthens the idea that defects could serve as topological morphogens and provides a number of predictions that could be tested in in vitro studies, for instance in the context of organoids.

Psychosocial health and quality of life in ICSI and naturally conceived adolescents: a cross-sectional comparison.

PURPOSE: Psychosocial health (PH) and quality of life (QoL) are important health outcomes. We compared PH and QoL of adolescents conceived with intrazytoplasmatic sperm injection (ICSI) and of naturally conceived controls. The impact of disclosure of ICSI-conception on QoL and PH was quantified. METHODS: The cross-sectional sample consisted of 545 ICSI-conceived adolescents and 427 unmatched singleton controls aged 14-18 years. Adolescents reported PH with the 'Strengths and Difficulties Questionnaire' (low values indicating high PH), and QoL with the KINDL questionnaire (high values indicating high QoL). Because of clustering of multiples within families, adjusted linear regressions with generalized estimating equations were used to compare ICSI- and naturally conceived adolescents. Missing values were treated by multiple imputation. Minimal importance was defined as half a standard deviation. RESULTS: Both ICSI and control adolescents had high PH (low mean 'total difficulties' score: 9 of 40) and high QoL (mean 'total KINDL' score: 75 of 100). Differences were generally in favour of the ICSI group. Significant differences occurred for 'impact of behavioural problems' (p = 0.033), the 'total KINDL' score (p = 0.021) and the dimensions 'physical wellbeing' (p = 0.031) and 'school' (p = 0.005), but all differences were far below minimal importance. About 80% of ICSI adolescents were informed about their mode of conception. PH and QoL were slightly higher in informed adolescents; behavioural difficulties ('total behavioural problems' and 'conduct problems') were significantly lower (p = 0.013 and p = 0.003), behavioural strengths ('prosocial behaviour') and 'physical QoL' significantly higher (p = 0.004 and p = 0.018), but differences remained clearly below minimal importance. CONCLUSIONS: Our results are reassuring for parents using ICSI and their children. Speaking openly about an ICSI conception in the family may be beneficial.

Toll-like receptor 3 expression in myeloid cells is essential for efficient regeneration after acute pancreatitis in mice.

Stringent regulation of the inflammatory response is crucial for normal tissue regeneration. Here, we analyzed the role of Toll-like receptor 3 (TLR3) in pancreatic regeneration after acute pancreatitis (AP). AP was induced by caerulein treatment in mice with global TLR3 deficiency (TLR3OFF ) or in mice re-expressing TLR3 exclusively in the myeloid cell lineage (TLR3Mye ). Compared to WT mice, TLR3OFF mice had a markedly increased formation of acinar-to-ductal metaplasia (ADM) that persisted until day 7 after initiation of AP. Pancreatic tissue of WT mice was completely regenerated after 5 days with no detectable ADM structures. The enhancing effect of TLR3-deficiency on ADM formation was closely linked with an increased and prolonged accumulation of macrophages in pancreata of TLR3OFF mice. Importantly, the phenotype of TLR3OFF mice was rescued in TLR3Mye mice, demonstrating the causative role of myeloid cell selective TLR3 signaling. Moreover, in vitro stimulation of macrophages through TLR3 initiated cell death by a caspase-8-associated mechanism. Therefore, these findings provide evidence that TLR3 signaling in myeloid cells is sufficient to limit inflammation and ADM formation and to promote regeneration after AP. Notably, resolution of inflammation after AP was associated with macrophage sensitivity to TLR3-mediated cell death.

Operator Scaling Dimensions and Multifractality at Measurement-Induced Transitions.

Repeated local measurements of quantum many-body systems can induce a phase transition in their entanglement structure. These measurement-induced phase transitions (MIPTs) have been studied for various types of dynamics, yet most cases yield quantitatively similar critical exponents, making it unclear how many distinct universality classes are present. Here, we probe the properties of the conformal field theories governing these MIPTs using a numerical transfer-matrix method, which allows us to extract the effective central charge, as well as the first few low-lying scaling dimensions of operators at these critical points for (1+1)-dimensional systems. Our results provide convincing evidence that the generic and Clifford MIPTs for qubits lie in different universality classes and that both are distinct from the percolation transition for qudits in the limit of large on-site Hilbert space dimension. For the generic case, we find strong evidence of multifractal scaling of correlation functions at the critical point, reflected in a continuous spectrum of scaling dimensions.

The Tukey trend test: Multiplicity adjustment using multiple marginal models.

In dose-response analysis, it is a challenge to choose appropriate linear or curvilinear shapes when considering multiple, differently scaled endpoints. It has been proposed to fit several marginal regression models that try sets of different transformations of the dose levels as explanatory variables for each endpoint. However, the multiple testing problem underlying this approach, involving correlated parameter estimates for the dose effect between and within endpoints, could only be adjusted heuristically. An asymptotic correction for multiple testing can be derived from the score functions of the marginal regression models. Based on a multivariate t-distribution, the correction provides a one-step adjustment of p-values that accounts for the correlation between estimates from different marginal models. The advantages of the proposed methodology are demonstrated through three example datasets, involving generalized linear models with differently scaled endpoints, differing covariates, and a mixed effect model and through simulation results. The methodology is implemented in an R package.

Coherent Beam Splitting of Flying Electrons Driven by a Surface Acoustic Wave.

We develop a coherent beam splitter for single electrons driven through two tunnel-coupled quantum wires by surface acoustic waves (SAWs). The output current through each wire oscillates with gate voltages to tune the tunnel coupling and potential difference between the wires. This oscillation is assigned to coherent electron tunneling motion that can be used to encode a flying qubit and is well reproduced by numerical calculations of time evolution of the SAW-driven single electrons. The oscillation visibility is currently limited to about 3%, but robust against decoherence, indicating that the SAW electron can serve as a novel platform for a solid-state flying qubit.

Unusual Near-Horizon Cosmic-Ray-like Events Observed by ANITA-IV.

ANITA's fourth long-duration balloon flight in 2016 detected 29 cosmic-ray (CR)-like events on a background of 0.37_{-0.17}^{+0.27} anthropogenic events. CRs are mainly seen in reflection off the Antarctic ice sheets, creating a phase-inverted waveform polarity. However, four of the below-horizon CR-like events show anomalous noninverted polarity, a p=5.3×10^{-4} chance if due to background. All anomalous events are from locations near the horizon; ANITA-IV observed no steeply upcoming anomalous events similar to the two such events seen in prior flights.

Steric Effects on the Thermal Processes of Hemithioindigo Based Molecular Motor Rotation.

Tuning the thermal behavior of light driven molecular motors is fundamentally important for their future rational design. In many molecular motors thermal ratcheting steps are comprised of helicity inversions, energetically stabilizing the initial photoproducts. In this work we investigated a series of five hemithioindigo (HTI) based molecular motors to reveal the influence of steric hindrance in close proximity to the rotation axle on this process. Applying a high yielding synthetic procedure, we synthesized constitutional isomeric derivatives to distinguish between substitution effects at the aromatic and aliphatic position on the rotor fragment. The kinetics of thermal helix inversions were elucidated using low temperature 1 H NMR spectroscopy and an in situ irradiation technique. In combination with a detailed theoretical description, a comparative analysis of substituent effects on the thermal helix inversions of the rotation cycle is now possible. Such deeper understanding of the rotational cycle of HTI molecular motors is essential for speed regulation and future applications of visible light triggered nanomachines.

Structural Evolution of Pt, Au and Cu Anodes by Electrolysis up to Contact Glow Discharge Electrolysis in Alkaline Electrolytes*.

Applying a voltage to metal electrodes in contact with aqueous electrolytes results in the electrolysis of water at voltages above the decomposition voltage and plasma formation in the electrolyte at much higher voltages referred to as contact glow discharge electrolysis (CGDE). While several studies explore parameters that lead to changes in the I-U characteristics in this voltage range, little is known about the evolution of the structural properties of the electrodes. Here we study this aspect on materials essential to electrocatalysis, namely Pt, Au, and Cu. The stationary I-U characteristics are almost identical for all electrodes. Detailed structural characterization by optical microscopy, scanning electron microscopy, and electrochemical approaches reveal that Pt is stable during electrolysis and CGDE, while Au and Cu exhibit a voltage-dependent oxide formation. More importantly, oxides are reduced when the Au and Cu electrodes are kept in the electrolysis solution after electrolysis. We suspect that H2 O2 (formed during electrolysis) is responsible for the oxide reduction. The reduced oxides (which are also accessible via electrochemical reduction) form a porous film, representing a possible new class of materials in energy storage and conversion studies.

Using historical control data in bioassays for regulatory toxicology.

Historical control data (HCD) consist of pooled control group responses from bioassays. These data must be collected and are often used or reported in regulatory toxicology studies for multiple purposes: as quality assurance for the test system, to help identify toxicological effects and their effect-size relevance and to address the statistical multiple comparison problem. The current manuscript reviews the various classical and potential new approaches for using HCD. Issues in current practice are identified and recommendations for improved use and discussion are provided. Furthermore, stakeholders are invited to discuss whether it is necessary to consider uncertainty when using HCD formally and statistically in toxicological discussions and whether binary inclusion/exclusion criteria for HCD should be revised to a tiered information contribution to assessments. Overall, the critical value of HCD in toxicological bioassays is highlighted when used in a weight-of-evidence assessment.

Mechanistic basis for the activation of plant membrane receptor kinases by SERK-family coreceptors.

Plant-unique membrane receptor kinases with leucine-rich repeat ectodomains (LRR-RKs) can sense small molecule, peptide, and protein ligands. Many LRR-RKs require SERK-family coreceptor kinases for high-affinity ligand binding and receptor activation. How one coreceptor can contribute to the specific binding of distinct ligands and activation of different LRR-RKs is poorly understood. Here we quantitatively analyze the contribution of SERK3 to ligand binding and activation of the brassinosteroid receptor BRI1 and the peptide hormone receptor HAESA. We show that while the isolated receptors sense their respective ligands with drastically different binding affinities, the SERK3 ectodomain binds the ligand-associated receptors with very similar binding kinetics. We identify residues in the SERK3 N-terminal capping domain, which allow for selective steroid and peptide hormone recognition. In contrast, residues in the SERK3 LRR core form a second, constitutive receptor-coreceptor interface. Genetic analyses of protein chimera between BRI1 and SERK3 define that signaling-competent complexes are formed by receptor-coreceptor heteromerization in planta. A functional BRI1-HAESA chimera suggests that the receptor activation mechanism is conserved among different LRR-RKs, and that their signaling specificity is encoded in the kinase domain of the receptor. Our work pinpoints the relative contributions of receptor, ligand, and coreceptor to the formation and activation of SERK-dependent LRR-RK signaling complexes regulating plant growth and development.

Electrodeposition of Zinc onto Au(111) and Au(100) from the Ionic Liquid [MPPip][TFSI].

The improvement of rechargeable zinc/air batteries was a hot topic in recent years. Predominantly, the influence of water and additives on the structure of the Zn deposit and the possible dendrite formation were studied. However, the effect of the surface structure of the underlying substrate was not focused on in detail, yet. We now show the differences in electrochemical deposition of Zn onto Au(111) and Au(100) from the ionic liquid N-methyl-N-propylpiperidinium bis(trifluoromethanesulfonyl)imide. The fundamental processes were initially characterized via cyclic voltammetry and in situ scanning tunnelling microscopy. Bulk deposits were then examined using Auger electron spectroscopy and scanning electron microscopy. Different structures of Zn deposits are observed during the initial stages of electrocrystallisation on both electrodes, which reveals the strong influence of the crystallographic orientation on the metal deposition of zinc on gold.

Versatile 3D-Printed Micro-Reference Electrodes for Aqueous and Non-Aqueous Solutions.

While numerous reference electrodes suitable for aqueous electrolytes exist, there is no well-defined standard for non-aqueous electrolytes. Furthermore, reference electrodes are often large and do not meet the size requirements for small cells. In this work, we present a simple method for fabricating stable 3D-printed micro-reference electrodes. The prints are made from polyvinylidene fluoride, which is chemically inert in strong acids, bases, and commonly used non-aqueous solvents. We chose six different reference systems based on Ag, Cu, Zn, and Na, including three aqueous and three non-aqueous systems to demonstrate the versatility of the approach. Subsequently, we conducted cyclic voltammetry experiments and measured the potential difference between the aqueous homemade reference electrodes and a commercial Ag/AgCl-electrode. For the non-aqueous reference electrodes, we chose the ferrocene redox couple as an internal standard. From these measurements, we deduced that this new class of micro-reference electrodes is leak-tight and shows a stable electrode potential.

Pubertal development and reproductive hormone levels of singleton ICSI offspring in adolescence: results of a prospective controlled study.

STUDY QUESTION: Are there any differences in the pubertal development and reproductive hormone status during adolescence between singletons following ICSI therapy or spontaneous conception (SC)? SUMMARY ANSWER: Pubertal development and reproductive hormone levels are largely similar between ICSI and SC adolescents, except for a tendency towards lower inhibin B levels as well as significantly higher estradiol levels and a lower testosterone-to-estradiol-ratio in male adolescents. WHAT IS KNOWN ALREADY: Previous data are scarce and partly inconclusive regarding pubertal development in female ICSI adolescents as well as demonstrating a tendency towards lower inhibin B serum levels in male ICSI offspring. STUDY DESIGN, SIZE, DURATION: Prospective controlled study including 274 singleton ICSI-conceived adolescents (141 girls, 133 boys) followed up for the third time, and 273 SC controls (142 girls, 131 boys) from seven German registration offices (Aachen, Eichstätt, Erfurt, Lübeck, Hamburg, Heidelberg and Schwerin). PARTICIPANTS/MATERIALS, SETTING, METHODS: Pubertal development assessed by Tanner staging (breast, genital and pubic hair development), age at menarche and reproductive hormone levels were analyzed in ICSI and SC adolescents at the mean age of 16.5 years. Differences were analyzed by multinomial regression (Tanner stages) or t test and linear regression for hormonal assessments. MAIN RESULTS AND THE ROLE OF CHANCE: Both female and male ICSI and SC adolescents showed adequate pubertal maturation according to their age, and the mean age at menarche (at 12.7 versus 12.8 years) was similar. Tanner stages as well did not display any relevant or significant differences between the groups. Reproductive hormone levels in female adolescents not using hormonal contraception were largely similar before and after adjustment for several factors such as preterm birth, Tanner stages, BMI or physical activity. In male ICSI adolescents, a tendency towards lower inhibin B (-14.8 pg/ml, 95% CI: -34.2 to 4.6 pg/ml), significantly higher estradiol (2.6 ng/l, 95% CI: 0.0 to 5.2 ng/l) and a significantly lower testosterone-to estradiol ratio (-0.047, 95% CI: -0.089 to -0.004) was found. LIMITATIONS, REASONS FOR CAUTION: The all-over response rate and the willingness to participate in the blood test and medical examination were very low in the control group. Participating control families may have greater health awareness, and selection bias cannot be ruled out. Hormonal data in the females were measured irrespective of the cycle day and restricted to those not using hormonal contraception. Some parameters from the questionnaire data such as usage of hormonal contraception might suffer from reporting bias. As this is an observational study, we can draw only limited causal conclusions from the findings. WIDER IMPLICATIONS OF THE FINDINGS: Differences in male reproductive hormones may indicate altered testicular function. However, at this time possible consequences for later reproductive success are unknown. STUDY FUNDING/COMPETING INTEREST(S): DFG research grant KA 1643/4-1. The authors declare no conflict of interest.

Measurement of Backaction from Electron Spins in a Gate-Defined GaAs Double Quantum dot Coupled to a Mesoscopic Nuclear Spin Bath.

Decoherence of a quantum system arising from its interaction with an environment is a key concept for understanding the transition between the quantum and classical world as well as performance limitations in quantum technology applications. The effects of large, weakly coupled environments are often described as a classical, fluctuating field whose dynamics is unaffected by the qubit, whereas a fully quantum description still implies some backaction from the qubit on the environment. Here we show direct experimental evidence for such a backaction for an electron-spin qubit in a GaAs quantum dot coupled to a mesoscopic environment of order 10^{6} nuclear spins. By means of a correlation measurement technique, we detect the backaction of a single qubit-environment interaction whose duration is comparable to the qubit's coherence time, even in such a large system. We repeatedly let the qubit interact with the spin bath and measure its state. Between such cycles, the qubit is reinitialized to different states. The correlations of the measurement outcomes are strongly affected by the intermediate qubit state, which reveals the action of a single electron spin on the nuclear spins.

Chiral stresses in nematic cell monolayers.

Recent experiments on monolayers of spindle-like cells plated on adhesive stripe-shaped domains have provided a convincing demonstration that certain types of collective phenomena in epithelia are well described by active nematic hydrodynamics. While recovering some of the hallmark predictions of this framework, however, these experiments have also revealed a number of unexpected features that could be ascribed to the existence of chirality over length scales larger than the typical size of a cell. In this article we elaborate on the microscopic origin of chiral stresses in nematic cell monolayers and investigate how chirality affects the motion of topological defects, as well as the collective motion in stripe-shaped domains. We find that chirality introduces a characteristic asymmetry in the collective cellular flow, from which the ratio between chiral and non-chiral active stresses can be inferred by particle-image-velocimetry measurements. Furthermore, we find that chirality changes the nature of the spontaneous flow transition under confinement and that, for specific anchoring conditions, the latter has the structure of an imperfect pitchfork bifurcation.

Socioeconomic and migration status as predictors of emergency caesarean section: a birth cohort study.

BACKGROUND: Women with a migration background are reportedly at a higher risk of emergency caesarean section. There is evidence that this is due in part to suboptimal antenatal care use and quality of care. Despite the fact that migrant women and descendants of migrants are often at risk of socioeconomic disadvantage, there is, in comparison, scarce and incomplete evidence on the role of socioeconomic position as an independent risk factor for emergency caesarean delivery. We therefore investigate whether and how migration background and two markers of socioeconomic position affect the risk of an emergency caesarean section and whether they interact with each other. METHODS: In 2013-2016, we recruited women during the perinatal period in Bielefeld, Germany, collecting data on health and socioeconomic and migration background, as well as routine perinatal data. We studied associations between migration background (1st generation migrant, 2nd/3rd generation woman, no migration background), socioeconomic status (educational attainment and net monthly household income), and the outcome emergency caesarean section. RESULTS: Of the 881 participants, 21% (n = 185) had an emergency caesarean section. Analyses showed no association between having an emergency caesarean section and migration status or education. Women in the lowest (< 800€/month) and second lowest (between 800 and 1750€/month) income categories were more likely (aOR: 1.96, CI: 1.01-3.81; and aOR: 2.36, CI: 1.27-4.40, respectively) to undergo an emergency caesarean section than women in the higher income groups. CONCLUSIONS: Migration status and education did not explain heterogeneity in mode of birth. Having a low household income, however, increased the chances of emergency caesarean section and thereby contributed towards producing health disadvantages. Awareness of these findings and measures to correct these inequalities could help to improve the quality of obstetric care.

Alternatives to statistical decision trees in regulatory (eco-)toxicological bioassays.

The goal of (eco-) toxicological testing is to experimentally establish a dose or concentration-response and to identify a threshold with a biologically relevant and probably non-random deviation from "normal". Statistical tests aid this process. Most statistical tests have distributional assumptions that need to be satisfied for reliable performance. Therefore, most statistical analyses used in (eco-)toxicological bioassays use subsequent pre- or assumption-tests to identify the most appropriate main test, so-called statistical decision trees. There are however several deficiencies with the approach, based on study design, type of tests used and subsequent statistical testing in general. When multiple comparisons are used to identify a non-random change against negative control, we propose to use robust testing, which can be generically applied without the need of decision trees. Visualization techniques and reference ranges also offer advantages over the current pre-testing approaches. We aim to promulgate the concepts in the (eco-) toxicological community and initiate a discussion for regulatory acceptance.

Use compatibility intervals in regulatory toxicology.

Recently it was recommended to avoid significance tests, in particular dichotomization into significant/non-significant on the basis of a p-value and a fixed 5% significance level (i.e. false positive rate). As an alternative, the interpretation of a suitable effect size and its compatibility interval is recommended, i.e. confidence intervals whose compatibility with the data, the assumptions, and the models is shown. This concept is used for the evaluation of assays in regulatory toxicology with special emphasis on the proof of hazard and proof of safety. Three case studies for multiple endpoints, multiple models and the consideration of historical controls illustrate the applicability of this concept. The corresponding software code for the open-source R project for statistical computing (www.r-project.org) is provided.

Optical Detection of Single-Electron Tunneling into a Semiconductor Quantum Dot.

The maximum information of a dynamic quantum system is given by real-time detection of every quantum event, where the ultimate challenge is a stable, sensitive detector with high bandwidth. All physical information can then be drawn from a statistical analysis of the time traces. We demonstrate here an optical detection scheme based on the time-resolved resonance fluorescence on a single quantum dot. Single-electron resolution with high signal-to-noise ratio (4σ confidence) and high bandwidth of 10 kHz make it possible to record the individual quantum events of the transport dynamics. Full counting statistics with factorial cumulants gives access to the nonequilibrium dynamics of spin relaxation of a singly charged dot (γ_{↑↓}=3 ms^{-1}), even in an equilibrium transport measurement.