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In toxicology, the validation of the concurrent control by historical control data (HCD) has become requirements. This validation is usually done by historical control limits (HCL) which in practice are often graphically displayed in a Sheward control chart like manner. In many applications, HCL are applied to dichotomous data, e.g. the number of rats with a tumor vs. the number of rats without a tumor (carcinogenicity studies) or the number of cells with a micronucleus out of a total number of cells. Dichotomous HCD may be overdispersed and can be heavily right- (or left-) skewed, which is usually not taken into account in the practical applications of HCL. To overcome this problem, four different prediction intervals (two frequentist, two Bayesian), that can be applied to such data, are proposed. Comprehensive Monte-Carlo simulations assessing the coverage probabilities of seven different methods for HCL calculation reveal, that frequentist bootstrap calibrated prediction intervals control the type-1-error best. Heuristics traditionally used in control charts (e.g. the limits in Sheward np-charts or the mean plus minus 2 SD) as well a the historical range fail to control a pre-specified coverage probability. The application of HCL is demonstrated based on a real life data set containing historical controls from long-term carcinogenicity studies run on behalf of the U.S. National Toxicology Program. The proposed frequentist prediction intervals are publicly available from the R package predint, whereas R code for the computation of the Bayesian prediction intervals is provided via GitHub.

In pre-clinical and medical quality control, it is of interest to assess the stability of the process under monitoring or to validate a current observation using historical control data. Classically, this is done by the application of historical control limits (HCL) graphically displayed in control charts. In many applications, HCL are applied to count data, e.g. the number of revertant colonies (Ames assay) or the number of relapses per multiple sclerosis patient. Count data may be overdispersed, can be heavily right-skewed and clusters may differ in cluster size or other baseline quantities (e.g. number of petri dishes per control group or different length of monitoring times per patient). Based on the quasi-Poisson assumption or the negative-binomial distribution, we propose prediction intervals for overdispersed count data to be used as HCL. Variable baseline quantities are accounted for by offsets. Furthermore, we provide a bootstrap calibration algorithm that accounts for the skewed distribution and achieves equal tail probabilities. Comprehensive Monte-Carlo simulations assessing the coverage probabilities of eight different methods for HCL calculation reveal, that the bootstrap calibrated prediction intervals control the type-1-error best. Heuristics traditionally used in control charts (e.g. the limits in Sheward c- or u-charts or the mean plus minus 2 SD) fail to control a pre-specified coverage probability. The application of HCL is demonstrated based on data from the Ames assay and for numbers of relapses of multiple sclerosis patients. The proposed prediction intervals and the algorithm for bootstrap calibration are publicly available via the R package predint.

Attempts to create quantum degenerate gases without evaporative cooling have been pursued since the early days of laser cooling, with the consensus that polarization gradient cooling (PGC, also known as "optical molasses") alone cannot reach condensation. In the present work, we report that simple PGC can generate a small Bose-Einstein condensate (BEC) inside a corrugated micrometer-sized optical dipole trap. The experimental parameters enabling BEC creation were found by machine learning, which increased the atom number by a factor of 5 and decreased the temperature by a factor of 2.5, corresponding to almost two orders of magnitude gain in phase space density. When the trapping light is slightly misaligned through a microscopic objective lens, a BEC of $\sim 250$ $^{87}$Rb atoms is formed inside a local dimple within 40 ms of PGC., Comment: 8 pages, 6 figures

A central goal in creating long-distance quantum networks and distributed quantum computing is the development of interconnected and individually controlled qubit nodes. Atom-like emitters in diamond have emerged as a leading system for optically networked quantum memories, motivating the development of visible-spectrum, multi-channel photonic integrated circuit (PIC) systems for scalable atom control. However, it has remained an open challenge to realize optical programmability with a qubit layer that can achieve high optical detection probability over many optical channels. Here, we address this problem by introducing a modular architecture of piezoelectrically-actuated atom-control PICs (APICs) and artificial atoms embedded in diamond nanostructures designed for high-efficiency free-space collection. The high-speed 4-channel APIC is based on a splitting tree mesh with triple-phase shifter Mach-Zehnder interferometers. This design simultaneously achieves optically broadband operation at visible wavelengths, high-fidelity switching ($> 40$ dB) at low voltages, sub-$\mu$s modulation timescales ($> 30$ MHz), and minimal channel-to-channel crosstalk for repeatable optical pulse carving. Via a reconfigurable free-space interconnect, we use the APIC to address single silicon vacancy color centers in individual diamond waveguides with inverse tapered couplers, achieving efficient single photon detection probabilities (15$\%$) and second-order autocorrelation measurements $g^{(2)}(0) < 0.14$ for all channels. The modularity of this distributed APIC - quantum memory system simplifies the quantum control problem, potentially enabling further scaling to 1000s of channels.

Advances in laser technology have driven discoveries in atomic, molecular, and optical (AMO) physics and emerging applications, from quantum computers with cold atoms or ions, to quantum networks with solid-state color centers. This progress is motivating the development of a new generation of "programmable optical control" systems, characterized by criteria (C1) visible (VIS) and near-infrared (IR) wavelength operation, (C2) large channel counts extensible beyond 1000s of individually addressable atoms, (C3) high intensity modulation extinction and (C4) repeatability compatible with low gate errors, and (C5) fast switching times. Here, we address these challenges by introducing an atom control architecture based on VIS-IR photonic integrated circuit (PIC) technology. Based on a complementary metal-oxide-semiconductor (CMOS) fabrication process, this Atom-control PIC (APIC) technology meets the system requirements (C1)-(C5). As a proof of concept, we demonstrate a 16-channel silicon nitride based APIC with (5.8$\pm$0.4) ns response times and -30 dB extinction ratio at a wavelength of 780 nm. This work demonstrates the suitability of PIC technology for quantum control, opening a path towards scalable quantum information processing based on optically-programmable atomic systems.

A prediction interval is a statistical interval that should encompass one (or more) future observation(s) with a given coverage probability and is usually computed based on historical control data. The application of prediction intervals is discussed in many fields of research, such as toxicology, pre-clinical statistics, engineering, assay validation or for the assessment of replication studies. Anyhow, the prediction intervals implemented in predint descent from previous work that was done in the context of toxicology and pre-clinical applications. Hence the implemented methodology reflects the data structures that are common in these fields of research. In toxicology the historical data is often comprised of dichotomous or counted endpoints. Hence it seems natural to model these kind of data based on the binomial or the Poisson distribution. Anyhow, the historical control data is usually comprised of several studies. These clustering gives rise to possible overdispersion which has to be reflected for interval calculation. In pre-clinical statistics, the endpoints are often assumed to be normal distributed, but usually are not independent from each other due to the experimental design (cross-classified and/or hierarchical structures). These dependencies can be modeled based on linear random effects models. Hence, predint provides functions for the calculation of prediction intervals and one-sided bounds for overdispersed binomial data, for overdispersed Poisson data and for data that is modeled by linear random effects models., Comment: 40 pages, 1 figure

In this work I demonstrate the interference of three photons, a generalisation of the famous Hong Ou Mandel (HOM) interference. I show that three-photon interference is governed by four parameters and measure three-photon interference independent of two-photon interference. I demonstrate that even when the states of the photons are highly distinguishable they can still exhibit strong quantum interference, challenging our intuition formed by the double slit and HOM interference. This is followed by a demonstration of four-photon interference, where surprisingly we can still observe a "fringe" when the involved particles are pairwise orthogonal. To explain these effects, I present a new framework to describe multi-photon interference in terms of a graph-theoretical approach, which illustrates the origin of different orders of multi-photon interference. My work leads to a more general definition of what we regard as an interference fringe in multi-photon scattering. This study of multi-photon interference is followed by an interdisciplinary work between photonics and solid state physics in the newly developing field of topological photonics. I realise a simulation of the Jackiw-Rossi model as a localised topological mode in a photonic-crystal analogue of the 2D graphene lattice. I succeed in the experimental demonstration of a single such excitation and I am able to study the detailed mode structure for the first time. The mode is a result of a topological defect and is, as such, protected against errors that do not change the topology of the system.

Solutions for scalable, high-performance optical control are important for the development of scaled atom-based quantum technologies. Modulation of many individual optical beams is central to the application of arbitrary gate and control sequences on arrays of atoms or atom-like systems. At telecom wavelengths, miniaturization of optical components via photonic integration has pushed the scale and performance of classical and quantum optics far beyond the limitations of bulk devices. However, these material platforms for high-speed telecom integrated photonics are not transparent at the short wavelengths required by leading atomic systems. Here, we propose and implement a scalable and reconfigurable photonic architecture for multi-channel quantum control using integrated, visible-light modulators based on thin-film lithium niobate. Our approach combines techniques in free-space optics, holography, and control theory together with a sixteen-channel integrated photonic device to stabilize temporal and cross-channel power deviations and enable precise and uniform control. Applying this device to a homogeneous constellation of silicon-vacancy artificial atoms in diamond, we present techniques to spatially and spectrally address a dynamically-selectable set of these stochastically-positioned point emitters. We anticipate that this scalable and reconfigurable optical architecture will lead to systems that could enable parallel individual programmability of large many-body atomic systems, which is a critical step towards universal quantum computation on such hardware., Comment: 16 pages, 15 figures

We study the impact of distinguishability and mixedness -- two fundamental properties of quantum states -- on quantum interference. We show that these can influence the interference of multiple particles in different ways, leading to effects that cannot be observed in the interference of two particles alone. This is demonstrated experimentally by interfering three independent photons in pure and mixed states and observing their different multiphoton interference, despite exhibiting the same two-photon Hong-Ou-Mandel (HOM) interference. Besides its fundamental relevance, our observation has important implications for quantum technologies relying on photon interference., Comment: 11 pages, 7 figures

Recent advances in photonic integrated circuits (PICs) have enabled a new generation of "programmable many-mode interferometers" (PMMIs) realized by cascaded Mach Zehnder Interferometers (MZIs) capable of universal linear-optical transformations on N input-output optical modes. PMMIs serve critical functions in photonic quantum information processing, quantum-enhanced sensor networks, machine learning and other applications. However, PMMI implementations reported to date rely on thermo-optic phase shifters, which limit applications due to slow response times and high power consumption. Here, we introduce a large-scale PMMI platform, based on a 200 mm CMOS process, that uses aluminum nitride (AlN) piezo-optomechanical actuators coupled to silicon nitride (SiN) waveguides, enabling low-loss propagation with phase modulation at greater than 100 MHz in the visible to near-infrared wavelengths. Moreover, the vanishingly low holding-power consumption of the piezo-actuators enables these PICs to operate at cryogenic temperatures, paving the way for a fully integrated device architecture for a range of quantum applications., Comment: 18 pages, 5 figures, 7 supplementary figures

One of the central principles of quantum mechanics is that if there are multiple paths that lead to the same event, and there is no way to distinguish between them, interference occurs. It is usually assumed that distinguishing information in the preparation, evolution or measurement of a system is sufficient to destroy interference. For example, determining which slit a particle takes in Young's double slit experiment or using distinguishable photons in the two-photon Hong-Ou-Mandel effect allow discrimination of the paths leading to detection events, so in both cases interference vanishes. Remarkably for more than three independent quantum particles, distinguishability of the prepared states is not a sufficient condition for multiparticle interference to disappear. Here we experimentally demonstrate this for four photons prepared in pairwise distinguishable states, thus fundamentally challenging intuition of multiparticle interference., Comment: 23 pages, 18 figures

Topological photonics sheds light on some of the surprising phenomena seen in condensed matter physics that arise with the appearance of topological invariants. Optical waveguides provide a well-controlled platform to investigate effects that relate to different topological phases of matter, providing insight into phenomena such as topological insulators and superconductors by direct simulation of the states that are protected by the topology of the system. Here, we observe a mode associated with a topological defect in the bulk of a 2D photonic material by introducing a vortex distortion to an hexagonal lattice and analogous to graphene. These observations are made possible by advances in our experimental methods. We were able to manufacture uniform large two-dimensional photonic crystal structures, containing thousands of identical waveguides arranged in two dimensions, and we developed a new method to excite multiples of these waveguides with a well-defined light field. This allows us to probe the detailed spatial features of topological defect modes for the first time. The observed modes lie mid-gap at zero energy and are closely related to Majorana bound states in superconducting vortices. This is the first experimental demonstration of a mode that is a solution to the Dirac equation in the presence of a vortex, as proposed by Jackiw and Rossi.

Photonic integrated circuits (PICs) directly written with a femtosecond laser have shown great potential in many areas such as quantum information processing (QIP). Many applications, like photon-based quantum computing, demand the up-scaling of PICs and ever-higher optical performance, such as controllable polarisation dependence and lower loss. In order to overcome current limitations in fabrication precision, repeatability and material uniformity, a solution for non-destructive testing of large-scale PICs in a component-wise manner is desired to meet those ever-stricter demands. Here we demonstrate a solution for non-destructive component-wise testing by predicting the performance of a PIC component based on imaging with an adaptive optical third-harmonic-generation (THG) three-dimensional (3D) microscope. The 3D THG imaging can be performed on any component or part of it inside multi-component PIC. Moreover, through discovering new phenomena we also demonstrated that 3D THG microscopy provides a new pathway towards studying the fundamentals of light-matter interaction in transparent materials.

We demonstrate how boson sampling with photons of partial distinguishability can be expressed in terms of interference of fewer photons. We use this observation to propose a classical algorithm to simulate the output of a boson sampler fed with photons of partial distinguishability. We find conditions for which this algorithm is efficient, which gives a lower limit on the required indistinguishability to demonstrate a quantum advantage. Under these conditions, adding more photons only polynomially increases the computational cost to simulate a boson sampling experiment.

Quantum interference of two independent particles in pure quantum states is fully described by the particles' distinguishability: the closer the particles are to being identical, the higher the degree of quantum interference. When more than two particles are involved, the situation becomes more complex and interference capability extends beyond pairwise distinguishability, taking on a surprisingly rich character. Here, we study many-particle interference using three photons. We show that the distinguishability between pairs of photons is not sufficient to fully describe the photons' behaviour in a scattering process, but that a collective phase, the triad phase, plays a role. We are able to explore the full parameter space of three-photon interference by generating heralded single photons and interfering them in a fibre tritter. Using multiple degrees of freedom - temporal delays and polarisation - we isolate three-photon interference from two-photon interference. Our experiment disproves the view that pairwise two-photon distinguishability uniquely determines the degree of non-classical many-particle interference.

We report on the observation of discrete structures in the electron energy distribution for strong field double ionization of Argon at 394 nm. The experimental conditions were chosen in order to ensure a non-sequential ejection of both electrons with an intermediate rescattering step. We have found discrete ATI (above-threshold ionization) like peaks in the sum energy of both electrons, as predicted by all quantum mechanical calculations. More surprisingly however is the observation of two ATI combs in the energy distribution of the individual electrons., Comment: Accepted for publication in Phys. Rev. Lett