A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution.

This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada. Substantial differences were identified in the legal requirements for risk assessment of combined exposure to multiple chemicals and its implementation between EU and non-EU countries and across several regulatory sectors. Frameworks currently proposed and in use for assessing risks from combined exposure to multiple chemicals via multiple routes and different durations of exposure are summarized. In order to avoid significant discrepancies between regulatory sectors or countries, the approach for assessing risks of combined exposure should be based on similar principles for all types of chemicals. OECD and EFSA identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area. The Horizon 2020 project "EuroMix" aims to contribute to the further development of internationally harmonized approaches for such risk assessments by the development of an integrated test strategy using in vitro and in silico tests verified for chemical mixtures based on more appropriate data on potential combined effects. These approaches and testing strategies should be integrated in a scientifically based weight of evidence approach to account for complexity and uncertainty, to improve risk assessment.

Coherent Coupling of Remote Spin Ensembles via a Cavity Bus.

We report coherent coupling between two macroscopically separated nitrogen-vacancy electron spin ensembles in a cavity quantum electrodynamics system. The coherent interaction between the distant ensembles is directly detected in the cavity transmission spectrum by observing bright and dark collective multiensemble states and an increase of the coupling strength to the cavity mode. Additionally, in the dispersive limit we show transverse ensemble-ensemble coupling via virtual photons.

The unsolved chapter of vocal fold scars and how tissue engineering could help us solve the problem.

Vocal fold scarring is a relatively small field in scar research with prerequisites found nowhere else. The deterioration of the delicate tri-layered micro-structure of the epithelium of the vocal folds leads to impaired vibration characteristics resulting in a permanent hoarse and breathy voice. Tissue engineering approaches could help to restore the pre-injury status. Despite a considerable progress in this field during the last years, routine clinical applications are not available so far. One reason might be that vocal fold fibroblasts, as the responsible cell type for fibrogenesis, have very particular properties that are only poorly characterized. Moreover, in vivo trials are costly and time consuming and a representative in vitro model does not exist so far. These particular circumstances lead to innovative in vitro strategies and concepts such as macro-molecular crowding that can also be applied in adjacent fields.

Gravity resonance spectroscopy constrains dark energy and dark matter scenarios.

We report on precision resonance spectroscopy measurements of quantum states of ultracold neutrons confined above the surface of a horizontal mirror by the gravity potential of Earth. Resonant transitions between several of the lowest quantum states are observed for the first time. These measurements demonstrate that Newton's inverse square law of gravity is understood at micron distances on an energy scale of 10-14 eV. At this level of precision, we are able to provide constraints on any possible gravitylike interaction. In particular, a dark energy chameleon field is excluded for values of the coupling constant ß>5.8×108 at 95% confidence level (C.L.), and an attractive (repulsive) dark matter axionlike spin-mass coupling is excluded for the coupling strength gsgp>3.7×10-16 (5.3×10-16) at a Yukawa length of λ=20 µm (95% C.L.).

Pump-induced exceptional points in lasers.

We demonstrate that the above-threshold behavior of a laser can be strongly affected by exceptional points which are induced by pumping the laser nonuniformly. At these singularities, the eigenstates of the non-Hermitian operator which describes the lasing modes coalesce. In their vicinity, the laser may turn off even when the overall pump power deposited in the system is increased. Such signatures of a pump-induced exceptional point can be experimentally probed with coupled ridge or microdisk lasers.

Chiral and degenerate perfect absorption on exceptional surfaces.

Engineering light-matter interactions using non-Hermiticity, particularly through spectral degeneracies known as exceptional points (EPs), is an emerging field with potential applications in areas such as cavity quantum electrodynamics, spectral filtering, sensing, and thermal imaging. However, tuning and stabilizing a system to a discrete EP in parameter space is a challenging task. Here, we circumvent this challenge by operating a waveguide-coupled resonator on a surface of EPs, known as an exceptional surface (ES). We achieve this by terminating only one end of the waveguide with a tuneable symmetric reflector to induce a nonreciprocal coupling between the frequency-degenerate clockwise and counterclockwise resonator modes. By operating the system at critical coupling on the ES, we demonstrate chiral and degenerate perfect absorption with squared-Lorentzian lineshape. We expect our approach to be useful for studying quantum processes at EPs and to serve as a bridge between non-Hermitian physics and other fields that rely on radiation engineering.

Topological modes in a laser cavity through exceptional state transfer.

Shaping the light emission characteristics of laser systems is of great importance in various areas of science and technology. In a typical lasing arrangement, the transverse spatial profile of a laser mode tends to remain self-similar throughout the entire cavity. Going beyond this paradigm, we demonstrate here how to shape a spatially evolving mode such that it faithfully settles into a pair of bi-orthogonal states at the two opposing facets of a laser cavity. This was achieved by purposely designing a structure that allows the lasing mode to encircle a non-Hermitian exceptional point while deliberately avoiding non-adiabatic jumps. The resulting state transfer reflects the unique topology of the associated Riemann surfaces associated with this singularity. Our approach provides a route to developing versatile mode-selective active devices and sheds light on the interesting topological features of exceptional points.

Cavity QED with magnetically coupled collective spin states.

We report strong coupling between an ensemble of nitrogen-vacancy center electron spins in diamond and a superconducting microwave coplanar waveguide resonator. The characteristic scaling of the collective coupling strength with the square root of the number of emitters is observed directly. Additionally, we measure hyperfine coupling to (13)C nuclear spins, which is a first step towards a nuclear ensemble quantum memory. Using the dispersive shift of the cavity resonance frequency, we measure the relaxation time of the NV center at millikelvin temperatures in a nondestructive way.

All-optical adaptive control of quantum cascade random lasers.

Spectral fingerprints of molecules are mostly accessible in the terahertz (THz) and mid-infrared ranges, such that efficient molecular-detection technologies rely on broadband coherent light sources at such frequencies. If THz Quantum Cascade Lasers can achieve octave-spanning bandwidth, their tunability and wavelength selectivity are often constrained by the geometry of their cavity. Here we introduce an adaptive control scheme for the generation of THz light in Quantum Cascade Random Lasers, whose emission spectra are reshaped by applying an optical field that restructures the permittivity of the active medium. Using a spatial light modulator combined with an optimization procedure, a beam in the near infrared (NIR) is spatially patterned to transform an initially multi-mode THz random laser into a tunable single-mode source. Moreover, we show that local NIR illumination can be used to spatially sense complex near-field interactions amongst modes. Our approach provides access to new degrees of freedom that can be harnessed to create broadly-tunable sources with interesting potential for applications like self-referenced spectroscopy.

Learning input correlations through nonlinear temporally asymmetric Hebbian plasticity.

Triggered by recent experimental results, temporally asymmetric Hebbian (TAH) plasticity is considered as a candidate model for the biological implementation of competitive synaptic learning, a key concept for the experience-based development of cortical circuitry. However, because of the well known positive feedback instability of correlation-based plasticity, the stability of the resulting learning process has remained a central problem. Plagued by either a runaway of the synaptic efficacies or a greatly reduced sensitivity to input correlations, the learning performance of current models is limited. Here we introduce a novel generalized nonlinear TAH learning rule that allows a balance between stability and sensitivity of learning. Using this rule, we study the capacity of the system to learn patterns of correlations between afferent spike trains. Specifically, we address the question of under which conditions learning induces spontaneous symmetry breaking and leads to inhomogeneous synaptic distributions that capture the structure of the input correlations. To study the efficiency of learning temporal relationships between afferent spike trains through TAH plasticity, we introduce a novel sensitivity measure that quantifies the amount of information about the correlation structure in the input, a learning rule capable of storing in the synaptic weights. We demonstrate that by adjusting the weight dependence of the synaptic changes in TAH plasticity, it is possible to enhance the synaptic representation of temporal input correlations while maintaining the system in a stable learning regime. Indeed, for a given distribution of inputs, the learning efficiency can be optimized.

Constant-intensity waves and their modulation instability in non-Hermitian potentials.

In all of the diverse areas of science where waves play an important role, one of the most fundamental solutions of the corresponding wave equation is a stationary wave with constant intensity. The most familiar example is that of a plane wave propagating in free space. In the presence of any Hermitian potential, a wave's constant intensity is, however, immediately destroyed due to scattering. Here we show that this fundamental restriction is conveniently lifted when working with non-Hermitian potentials. In particular, we present a whole class of waves that have constant intensity in the presence of linear as well as of nonlinear inhomogeneous media with gain and loss. These solutions allow us to study the fundamental phenomenon of modulation instability in an inhomogeneous environment. Our results pose a new challenge for the experiments on non-Hermitian scattering that have recently been put forward.

Neural dynamics in cortical networks--precision of joint-spiking events.

Electrophysiological studies of cortical function on the basis of multiple single-neuron recordings reveal neuronal interactions which depend on stimulus context and behavioural events. These interactions exhibit dynamics on different time scales, with time constants down to the millisecond range. Mechanisms underlying such dynamic organization of the cortical network were investigated by experimental and theoretical approaches. We review some recent results from these studies, concentrating on the occurrence of precise joint-spiking events in cortical activity, both in physiological and in model neural networks. These findings suggest that a combinatorial neural code, based on rapid associations of groups of neurons co-ordinating their activity at the single spike level, is biologically feasible.

Wound healing in nude mice: a study on the regulatory role of lymphocytes in fibroplasia.

In order to understand the role of T cells in postinjury fibroplasia, we have studied wound healing in congenitally athymic nude mice that lack a normally developed T cell system. Healing of incisional wounds, as assessed by wound breaking strength, was significantly stronger in nude mice compared with normal thymus-bearing animals. This was accompanied by a marked increase in the amount of reparative collagen synthesized at the wound site, as assessed by the hydroxyproline content of subcutaneously implanted sponges. Because nude mice have some extrathymic T cell maturation, we used an anti-Thy-1.2 (30H12) monoclonal antibody to selectively deplete T cells in vivo. Although such treatments impaired wound healing in normal mice, they had no effect on any wound healing parameter in nude mice. In a separate experiment, T cell reconstitution of nude mice, sufficient to significantly enhance in vivo delayed hypersensitivity responses, led to a decrease in both wound breaking strength and hydroxyproline deposition in subcutaneously implanted polyvinyl sponges. The data suggest that T cells play a dual role in wound healing: an early stimulatory role on macrophages, endothelial cells, and fibroblasts, and a late counterregulatory role, which may be responsible for the orderly completion of wound repair.

Single-trial estimation of neuronal firing rates: from single-neuron spike trains to population activity.

We present a method to estimate the neuronal firing rate from single-trial spike trains. The method, based on convolution of the spike train with a fixed kernel function, is calibrated by means of simulated spike trains for a representative selection of realistic dynamic rate functions. We derive rules for the optimized use and performance of the kernel method, specifically with respect to an effective choice of the shape and width of the kernel functions. An application of our technique to the on-line, single-trial reconstruction of arm movement trajectories from multiple single-unit spike trains using dynamic population vectors illustrates a possible use of the proposed method.

MEA-Tools: an open source toolbox for the analysis of multi-electrode data with MATLAB.

Recent advances in electrophysiological techniques have created new tools for the acquisition and storage of neuronal activity recorded simultaneously with numerous electrodes. These techniques support the analysis of the function as well as the structure of individual electrogenic cells in the context of surrounding neuronal or cardiac network. Commercially available tools for the analysis of such data, however, cannot be easily adapted to newly emerging requirements for data analysis and visualization, and cross compatibility between them is limited. In this report we introduce a free open source toolbox called microelectrode array tools (MEA-Tools) for the analysis of multi-electrode data based on the common data analysis environment MATLAB (version 5.3-6.1, The Mathworks, Natick, MA). The toolbox itself is platform independent. The file interface currently supports files recorded with MCRack (Multi Channel Systems, Reutlingen, Germany) under Microsoft Windows 95, 98, NT, and 2000, but can be adapted to other data acquisition systems. Functions are controlled via command line input and graphical user interfaces, and support common requirements for the analysis of local field potentials, extracellular spike activity, and continuous recordings, in addition to supplementary data acquired by additional instruments, e.g. intracellular amplifiers. Data may be processed as continuous recordings or time windows triggered to some event.

Tunable Fano resonances in transport through microwave billiards.

We present a tunable microwave scattering device that allows the controlled variation of Fano line shape parameters in transmission through quantum billiards. Transport in this device is nearly fully coherent. By comparison with quantum calculations, employing the modular recursive Green's-function method, the scattering wave function and the degree of residual decoherence can be determined. The parametric variation of Fano line shapes in terms of interacting resonances is analyzed.

Accurate spike synchronization in cortex.

In view of the enormous capacity and complexity of mammalian brains it is evident that a detailed account of their anatomy and physiology alone cannot lead to a complete understanding of their function. Computer simulation and mathematical analysis of abstract, yet biologically realistic models for neurons and networks yield additional and useful information about the interplay of the underlying anatomical structures, the physiological processes operating on the neuronal substrate, and the resulting brain functions during the performance of behavioral tasks. We discuss some contributions of such experiment-guided theory to the issue of accurate spike synchronization.

The single-channel regime of transport through random media.

The propagation of light through samples with random inhomogeneities can be described by way of transmission eigenchannels, which connect incoming and outgoing external propagating modes. Although the detailed structure of a disordered sample can generally not be fully specified, these transmission eigenchannels can nonetheless be successfully controlled and used for focusing and imaging light through random media. Here we demonstrate that in deeply localized quasi-1D systems, the single dominant transmission eigenchannel is formed by an individual Anderson-localized mode or by a 'necklace state'. In this single-channel regime, the disordered sample can be treated as an effective 1D system with a renormalized localization length, coupled through all the external modes to its surroundings. Using statistical criteria of the single-channel regime and pulsed excitations of the disordered samples allows us to identify long-lived localized modes and short-lived necklace states at long and short time delays, respectively.