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BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (SNT) is a treatment modality for Parkinson's Disease (PD). Either single central trajectory tract or multiple selected trajectory tracts based on microelectrode recordings (MER) are used for the placement of the final stimulating electrodes. This study aims to explore how many times trajectory tracts, other than the central tract are used for final lead placement. METHODS: Retrospective analysis of a randomly selected convenience sample of 24 subjects from patients who had DBS by a single neurosurgeon. After MRI and CT assessment, planning using a stereotactic frame for variable trajectory placement of temporary electrodes and MER that was the basis for site and tract selection for the final electrode placements used for DBS. RESULTS: Twenty four patients had 47 DBS electrodes placed: 1 unilateral and 23 bilateral. The central tract was used in 45 (95.75%) of these cases. The central trajectory tract accounted for 30 (63.83%), the anterior trajectory tract for 7 (14.89%), the medial tract for 5 (10.64%), the posterior for 4 (8.51%) and the lateral for 1 (2.13%) of final lead placements. CONCLUSION: The results of this study based on the predicted best stimulating sites following MER show that alternates to the central trajectory tract are required in 37% of site placements. A comparative study exploring clinical benefit is required to assess if variable electrode trajectory placement based on accurate physiological measurements is superior to single central trajectory placement.

The development of alternative platforms for computing has been a longstanding goal for physics, and represents a particularly pressing concern as conventional transistors approach the limit of miniaturization. A potential alternatice paradigm is that of reservoir computing, which leverages unknown, but highly non-linear transformations of input-data to perform computations. This has the advantage that many physical systems exhibit precisely the type of non-linear input-output relationships necessary for them to function as reservoirs. Consequently, the quantum effects which obstruct the further development of silicon electronics become an advantage for a reservoir computer. Here we demonstrate that even the most basic constituents of matter - atoms - can act as a reservoir for optical computers, thanks to the phenomenon of High Harmonic Generation (HHG). A prototype single-atom computer for classification problems is proposed, where parameters of the classification model are mapped to optical elements. We numerically demonstrate that this `all-optical' computer can successfully classify data with an accuracy that is strongly dependent on dynamical non-linearities. This may pave the way for the development of petahertz information processing platforms., 5 pages, 6 figures

Stem cell division is linked to tumorigenesis by yet-elusive mechanisms. The hematopoietic system reacts to stress by triggering hematopoietic stem and progenitor cell (HSPC) proliferation, which can be accompanied by chromosomal breakage in activated hematopoietic stem cells (HSCs). However, whether these lesions persist in their downstream progeny and induce a canonical DNA damage response (DDR) remains unclear. Inducing HSPC proliferation by simulated viral infection, we report that the associated DNA damage is restricted to HSCs and that proliferating HSCs rewire their DDR upon endogenous and clastogen-induced damage. Combining transcriptomics, single-cell and single-molecule assays on murine bone marrow cells, we found accelerated fork progression in stimulated HSPCs, reflecting engagement of PrimPol-dependent repriming, at the expense of replication fork reversal. Ultimately, competitive bone marrow transplantation revealed the requirement of PrimPol for efficient HSC amplification and bone marrow reconstitution. Hence, fine-tuning replication fork plasticity is essential to support stem cell functionality upon proliferation stimuli. Sí

Recent progress in nonlinear optical materials and microresonators has brought quantum computing with bulk optical nonlinearities into the realm of possibility. This platform is of great interest, not only because photonics is an obvious choice for quantum networks, but also as a promising route to quantum information processing at room temperature. We propose an approach for reprogrammable room-temperature photonic quantum logic that significantly simplifies the realization of various quantum circuits, and in particular, of error correction. The key element is the programmable photonic multi-mode resonator that implements reprogrammable bosonic quantum logic gates, while using only the bulk χ(2) nonlinear susceptibility. We theoretically demonstrate that just two of these elements suffice for a complete, compact error-correction circuit on a bosonic code, without the need for measurement or feed-forward control. Encoding and logical operations on the code are also easily achieved with these reprogrammable quantum photonic processors. An extrapolation of current progress in nonlinear optical materials and photonic circuits indicates that such circuitry should be achievable within the next decade., Photonic quantum computation via bulk optical nonlinearities presents challenges, due to the weakness of nonlinearity and the difficulties in doing without feed-forward control. Here, the authors propose an all-unitary approach that is based on a triply-resonant cavity with a time-dependent drive.

We propose and experimentally demonstrate an efficient scheme for bidirectional and deterministic photonic communication between two remote superconducting modules. The two chips, each consists of a transmon, are connected through a one-meter long coaxial cable that is coupled to a dedicated “communication” resonator on each chip. The two communication resonators hybridize with a mode of the cable to form a dark “communication mode” that is highly immune to decay in the coaxial cable. We overcome the various restrictions of quantum communication channels established by other recent approaches in deterministic communication for superconducting qubits. Our approach enables bidirectional communication, and eliminates the high insertion loss and large volume footprint of circulators. We modulate the transmon frequency via a parametric drive to generate sideband interactions between the transmon and the communication mode. We demonstrate bidirectional single-photon transfer with a success probability exceeding 60%, and generate an entangled Bell pair with a fidelity of 79.3 ± 0.3%. Quantum information can be passed between qubit devices by using nonlinear interactions to control transmission through a connecting cable. The construction of quantum networks and larger-scale quantum computers requires interconnections that can coherently transfer quantum information over long distances and between separate computing modules. Recent experiments have used controlled emission and absorption of microwave photons to produce one-way transmission between superconducting circuits. Nelson Leung and Yao Lu from the University of Chicago, with collaborators in the USA, have demonstrated two-way communication through a one-metre long coaxial cable. Manipulating the nonlinearities of their superconducting circuits via external controls allows the coupling between the qubits and the cable, and hence the inter-module transmission, to be turned on and off as necessary. This approach avoids some of the drawbacks of other quantum communication solutions with one-way transmission.

A central goal in photonic quantum information processing is the ability to perform high-fidelity logic gates between multiple optical qubits. Here, we present our recent theoretical work on using optical nonlinearities to implement controlled-phase gates between two optical qubits. Our approach is based on using dynamically coupled cavities to convert photons travelling in a waveguide into highly confined cavity modes. This conversion enables very strong interactions between photons in quasi-monochromatic modes, which enables high fidelity gates. We will discuss gate protocols based on second- and third order nonlinear materials as well as interactions with two-level emitters.

This work details a deterministic ensemble method for evolving open quantum systems and compare it with stochastic techniques.

In trapped-ion quantum information processing, interactions between spins (qubits) are mediated by collective modes of motion of an ion crystal. While there are many different experimental strategies to design such interactions, they all face both technical and fundamental limitations to the achievable coherent interaction strength. In general, obtaining strong interactions and fast gates is an ongoing challenge. Here, we extend previous work [W. Ge, B. C. Sawyer, J. W. Britton, K. Jacobs, J. J. Bollinger, and M. Foss-Feig, Phys. Rev. Lett. 122, 030501 (2019)] and present a general strategy for enhancing the interaction strengths in trapped-ion systems via parametric amplification of the ions’ motion. Specifically, we propose a stroboscopic protocol using alternating applications of parametric amplification and spin-motion coupling. In comparison with the previous work, we show that the current protocol can lead to larger enhancements in the coherent interaction that increase exponentially with the gate time.

We present a framework to control and track the observables of a general solid state system driven by an incident laser field. The main result is a non-linear equation of motion for tracking an observable, together with a constraint on the size of expectations which may be reproduced via tracking. Among other applications, this model provides a potential route to the design of laser fields which cause photo-induced superconductivity in materials above their critical temperature. As a first test, the strategy is used to make the expectation value of the current conform to an arbitrary function under a range of model parameters. Additionally, using two reference spectra for materials in the conducting and insulating regimes respectively, the tracking algorithm is used to make each material mimic the optical spectrum of the other., Comment: 5 pages, 3 figures, will be accompanied by an extended submission

Pursuing room-temperature quantum hardware, we discuss multi-mode optical cavities with nonlinear couplings and focus on material and fabrication requirements for such devices. We demonstrate their use for a number of quantum communication and computation tasks.

Networking superconducting quantum computers is a longstanding challenge in quantum science. The typical approach has been to cascade transducers: converting to optical frequencies at the transmitter and to microwave frequencies at the receiver. However, the small microwave-optical coupling and added noise have proven formidable obstacles. Instead, we propose optical networking via heralding end-to-end entanglement with one detected photon and teleportation. This new protocol can be implemented on standard transduction hardware while providing significant performance improvements over transduction. In contrast to cascaded direct transduction, our scheme absorbs the low optical-microwave coupling efficiency into the heralding step, thus breaking the rate-fidelity trade-off. Moreover, this technique unifies and simplifies entanglement generation between superconducting devices and other physical modalities in quantum networks.

Besides its role in homologous recombination, the tumor suppressor BRCA2 protects stalled replication forks from nucleolytic degradation. Defective fork stability contributes to chemotherapeutic sensitivity of BRCA2-defective tumors by yet-elusive mechanisms. Using DNA fiber spreading and direct visualization of replication intermediates, we report that reversed replication forks are entry points for fork degradation in BRCA2-defective cells. Besides MRE11 and PTIP, we show that RAD52 promotes stalled fork degradation and chromosomal breakage in BRCA2-defective cells. Inactivation of these factors restores reversed fork frequency and chromosome integrity in BRCA2-defective cells. Conversely, impairing fork reversal prevents fork degradation, but increases chromosomal breakage, uncoupling fork protection, and chromosome stability. We propose that BRCA2 is dispensable for RAD51-mediated fork reversal, but assembles stable RAD51 nucleofilaments on regressed arms, to protect them from degradation. Our data uncover the physiopathological relevance of fork reversal and illuminate a complex interplay of homologous recombination factors in fork remodeling and stability., BRCA2 is involved in both homologous recombination (HR) and the protection of stalled replication forks from degradation. Here the authors reveal how HR factors cooperate in fork remodeling, showing that BRCA2 supports RAD51 loading on the regressed arms of reversed replication forks to protect them from degradation.

We show that relatively simple integrated photonic circuits have the potential to realize a high fidelity deterministic controlled-phase gate between photonic qubits using bulk optical nonlinearities. The gate is enabled by converting travelling continuous-mode photons into stationary cavity modes using strong classical control fields that dynamically change the effective cavity-waveguide coupling rate. This architecture succeeds because it reduces the wave packet distortions that otherwise accompany the action of optical nonlinearities [J. Shapiro, Phys. Rev. A 73, 062305 (2006)PLRAAN1050-294710.1103/PhysRevA.73.062305; J. Gea-Banacloche, Phys. Rev. A 81, 043823 (2010)PLRAAN1050-294710.1103/PhysRevA.81.043823]. We show that high-fidelity gates can be achieved with self-phase modulation in χ^{(3)} materials as well as second-harmonic generation in χ^{(2)} materials. The gate fidelity asymptotically approaches unity with increasing storage time for an incident photon wave packet with fixed duration. We also show that dynamically coupled cavities enable a trade-off between errors due to loss and wave packet distortion. Our proposed architecture represents a new approach to practical implementation of quantum gates that is room-temperature compatible and only relies on components that have been individually demonstrated.

We study theoretically the interaction between two photons in a nonlinear cavity. The photons are absorbed into the cavity by an effective tuning of its input-output coupling via external control of a coupling to a second, strongly output-coupled cavity mode. Such ``dynamically coupled'' cavities, which can be implemented using bulk ${\ensuremath{\chi}}^{(2)}$ and ${\ensuremath{\chi}}^{(3)}$ nonlinearities, enable incoming photon wave packets to be absorbed into the cavity with high fidelity when the duration of the control is similar to that of the wave packets. Further, this configuration can be used to avoid limitations in the photon-photon interaction time set by the delay-bandwidth product of passive cavities and enables the elimination of wave-packet distortions caused by dispersive cavity transmission and reflection. We consider three kinds of nonlinearities, two arising from ${\ensuremath{\chi}}^{(2)}$ and ${\ensuremath{\chi}}^{(3)}$ materials and one due to an interaction with a two-level emitter. To analyze the input and output of few-photon wave packets, we use a Schr\"odinger-picture formalism in which traveling-wave fields are discretized into infinitesimal time bins. We suggest that dynamically coupled cavities provide a very useful tool for improving the performance of quantum devices relying on cavity-enhanced light-matter interactions such as single-photon sources and atomlike quantum memories with photon interfaces. As an example, we present simulation results showing that high-fidelity two-qubit entangling gates may be constructed using any of the considered nonlinear interactions.

Background & Aims Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. While the disruption of several IEC death regulating factors result in intestinal inflammation, the loss of the anti-apoptotic BCL2 family members BCL2 and BCL2L1 has no effect on intestinal homeostasis in mice. We investigated the functions of the antiapoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice. Methods We generated mice with IEC-specific disruption of Mcl1 (Mcl1ΔIEC mice) or tamoxifen-inducible IEC-specific disruption of Mcl1 (i-Mcl1ΔIEC mice); these mice and mice with full-length Mcl1 (controls) were raised under normal or germ-free conditions. Mice were analyzed by endoscopy and for intestinal epithelial barrier permeability. Intestinal tissues were analyzed by histology, in situ hybridization, proliferation assays, and immunoblots. Levels of calprotectin, a marker of intestinal inflammation, were measured in intestinal tissues and feces. Results Mcl1ΔIEC mice spontaneously developed apoptotic enterocolopathy, characterized by increased IEC apoptosis, hyperproliferative crypts, epithelial barrier dysfunction, and chronic inflammation. Loss of MCL1 retained intestinal crypts in a hyperproliferated state and prevented the differentiation of intestinal stem cells. Proliferation of intestinal stem cells in MCL1-deficient mice required WNT signaling and was associated with DNA damage accumulation. By 1 year of age, Mcl1ΔIEC mice developed intestinal tumors with morphologic and genetic features of human adenomas and carcinomas. Germ-free housing of Mcl1ΔIEC mice reduced markers of microbiota-induced intestinal inflammation but not tumor development. Conclusion The antiapoptotic protein MCL1, a member of the BCL2 family, is required for maintenance of intestinal homeostasis and prevention of carcinogenesis in mice. Loss of MCL1 results in development of intestinal carcinomas, even under germ-free conditions, and therefore does not involve microbe-induced chronic inflammation. Mcl1ΔIEC mice might be used to study apoptotic enterocolopathy and inflammatory bowel diseases., Graphical abstract

Realistic models of quantum systems must include dissipative interactions with an environment. For weakly-damped systems the Lindblad-form Markovian master equation is invaluable for this task due to its tractability and efficiency. This equation only applies, however, when the frequencies of any subset of the system's transitions are either equal (degenerate), or their differences are much greater than the transitions' linewidths (far-detuned). Outside of these two regimes the only available efficient description has been the Bloch-Redfield (B-R) master equation, the efficacy of which has long been controversial due to its failure to guarantee the positivity of the density matrix. The ability to efficiently simulate weakly-damped systems across all regimes is becoming increasingly important, especially in the area of quantum technologies. Here we solve this long-standing problem. We discover that a condition on the slope of the spectral density is sufficient to derive a Lindblad form master equation that is accurate for all regimes. We further show that this condition is necessary for weakly-damped systems to be described by the B-R equation or indeed any Markovian master equation. We thus obtain a replacement for the B-R equation over its entire domain of applicability that is no less accurate, simpler in structure, completely positive, allows simulation by efficient quantum trajectory methods, and unifies the previous Lindblad master equations. We also show via exact simulations that the new master equation can describe systems in which slowly-varying transition frequencies cross each other during the evolution. System identification tools, developed in systems engineering, play an important role in our analysis. We expect these tools to prove useful in other areas of physics involving complex systems., Comment: Revtex4-1, 16 pages, 7 png figures. v2: contains significant new material

The nonclassical properties of quantum states are of tremendous interest due to their potential applications in future technologies. It has recently been realized that the concept of a "resource theory" is a powerful approach to quantifying and understanding nonclassicality. To realize the potential of this approach one must first find resource theoretic measures of nonclassicality that are "operational", meaning that they also quantify the ability of quantum states to provide enhanced performance for specific tasks, such as precision sensing. Here we achieve a significant milestone in this endeavor by presenting the first such operational resource theoretic measure. In addition to satisfying the requirements of a resource measure, it has the closest possible relationship to the quantum-enhancement provided by a non-classical state for measuring phase-space displacement: it is equal to this enhancement for pure states, and is a tight upper bound on it for mixed states. We also show that a lower-bound on this measure can be obtained experimentally using a simple Mach-Zehnder interferometer., Comment: 8 pages, 1 figure, Updated

Summary Human embryonic stem cells (hESC) show great promise for clinical and research applications, but their well-known proneness to genomic instability hampers the development to their full potential. Here, we demonstrate that medium acidification linked to culture density is the main cause of DNA damage and genomic alterations in hESC grown on feeder layers, and this even in the short time span of a single passage. In line with this, we show that increasing the frequency of the medium refreshments minimizes the levels of DNA damage and genetic instability. Also, we show that cells cultured on laminin-521 do not present this increase in DNA damage when grown at high density, although the (long-term) impact on their genomic stability remains to be elucidated. Our results explain the high levels of genome instability observed over the years by many laboratories worldwide, and show that the development of optimal culture conditions is key to solving this problem., Graphical Abstract, Highlights • Increased culture density induces DNA damage and genomic alterations in hESC • Medium acidification due to lactic acid accumulation is the main driver • More frequent medium refreshments rescues genomic integrity in high-density culture • Laminin-521 reduces DNA damage but has no clear effect on genomic instability, In this article, Spits and colleagues show that the culture density of hESC is directly correlated to increased DNA damage and genomic instability. This is caused by medium acidification and can be countered by more frequent medium refreshments. When cultured on laminin-521, hESC show less DNA damage than in the feeder-based system, but no clear difference in genomic instability was found.

Human pluripotent stem cells have the capacity to self-renew indefinitely and the ability to differentiate into all cell types of a human body. These characteristics instill them with an enormous promise in regenerative medicine, where they could be used in cell, tissue and even organ-based replacement therapy. In this review, we discuss their potential clinical applications and the advantages and pitfalls for the different types of human pluripotent stem cells to transition from the bench to the bedside. We provide an overview of the current clinical trials, and the specific challenges we are still facing, including immune compatibility, suboptimal differentiation, risk of tumour formation and genome instability.

We discuss a general method of model selection from experimentally recorded time-trace data. This method can be used to distinguish between quantum and classical dynamical models. It can be used in post-selection as well as for real-time analysis, and offers an alternative to statistical tests based on state-reconstruction methods. We examine the conditions that optimize quantum hypothesis testing, maximizing one's ability to discriminate between classical and quantum models. We set upper limits on the temperature and lower limits on the measurement efficiencies required to explore these differences, using a novel experiment in levitated optomechanical systems as an example., 9 pages, 1 figure. Accepted for publication in Physical Review A (Rapid Communication)

Input-output theory is invaluable for treating superconducting and photonic circuits connected by transmission lines or waveguides. However, this theory cannot in general handle situations in which retro-reflections from circuit components or configurations of beam-splitters create loops for the traveling-wave fields that connect the systems. Here, building upon the network-contraction theory of Gough and James [Commun. Math. Phys. 287, 1109 (2009)], we provide a compact and powerful method to treat any circuit that contains such loops so long as the effective cavities formed by the loops are sufficiently weak. Essentially all present-day on-chip superconducting and photonic circuits will satisfy this weakness condition so long as the reflectors that form the loops are not especially highly reflecting. As an example we analyze the problem of transmitting entanglement between two qubits connected by a transmission line with imperfect circulators, a problem for which the new method is essential. We obtain a full solution for the optimal receiver given that the sender employs a simple turn on/turn off. This solution shows that near-perfect transmission is possible even with significant retro-reflections., 17 pages, 3 eps figures. v2: some pedagogical improvements to the presentation

The wave-function Monte-Carlo method, also referred to as the use of "quantum-jump trajectories", allows efficient simulation of open systems by independently tracking the evolution of many pure-state "trajectories". This method is ideally suited to simulation by modern, highly parallel computers. Here we show that Krotov's method of numerical optimal control, unlike others, can be modified in a simple way, so that it becomes fully parallel in the pure states without losing its effectiveness. This provides a highly efficient method for finding optimal control protocols for open quantum systems and networks. We apply this method to the problem of generating entangled states in a network consisting of systems coupled in a unidirectional chain. We show that due to the existence of a dark-state subspace in the network, nearly-optimal control protocols can be found for this problem by using only a single pure-state trajectory in the optimization, further increasing the efficiency., 17 pages, 4 figures

It is known that placing a mechanical oscillator in a superposition of coherent states allows, in theory, a measurement of a linear force whose sensitivity increases with the amplitude of the mechanical oscillations, a uniquely quantum effect. Further, entangled versions of these states across a network of $n$ mechanical oscillators enables a measurement whose sensitivity increases linearly with $n$, thus improving over the classical scaling by $\sqrt{n}$. One of the key challenges in exploiting this effect is processing the signal so that it can be readily measured; linear processing is insufficient. Here we show that a Kerr oscillator will not only create the necessary states, but also perform the required processing, transforming the quantum phase imprinted by the force signal into a shift in amplitude measurable with homodyne detection. This allows us to design a relatively simple quantum electro-mechanical circuit that can demonstrate the core quantum effect at the heart of this scheme, amplitude-dependent force sensitivity. We derive analytic expressions for the performance of the circuit, including thermal mechanical noise and photon loss. We discuss the experimental challenges in implementing the scheme with near-term technology., Comment: 5 pages, Revetex 4, 1 png figure

We derive a bound on the ability of a linear-optical network to estimate a linear combination of independent phase shifts by using an arbitrary nonclassical but unentangled input state, thereby elucidating the quantum resources required to obtain the Heisenberg limit with a multiport interferometer. Our bound reveals that while linear networks can generate highly entangled states, they cannot effectively combine quantum resources that are well distributed across multiple modes for the purposes of metrology: In this sense, linear networks endowed with well-distributed quantum resources behave classically. Conversely, our bound shows that linear networks can achieve the Heisenberg limit for distributed metrology when the input photons are concentrated in a small number of input modes, and we present an explicit scheme for doing so.

A candidate for converting quantum information from microwave to optical frequencies is the use of a single atom that interacts with a superconducting microwave resonator on one hand and an optical cavity on the other. The large electric dipole moments and microwave transition frequencies possessed by Rydberg states allow them to couple strongly to superconducting devices. Lasers can then be used to connect a Rydberg transition to an optical transition to realize the conversion. Since the fundamental source of noise in this process is spontaneous emission from the atomic levels, the resulting control problem involves choosing the pulse shapes of the driving lasers so as to maximize the transfer rate while minimizing this loss. Here we consider the concrete example of a cesium atom, along with two specific choices for the levels to be used in the conversion cycle. Under the assumption that spontaneous emission is the only significant source of errors, we use numerical optimization to determine the likely rates for reliable quantum communication that could be achieved with this device. These rates are on the order of a few Mega-qubits per second., Comment: 11 pages, 4 pdf figures, 2 png figures, Revtex4-1. v2: correction to metadata only

In this mainly pedagogical article, we discuss under what circumstances measurements play a special role in quantum processes. In particular, we discuss the following facts that appear to be a common area of confusion. (i) From a fundamental point of view, measurements play no special role whatsoever: all dynamics that can be generated by measurements can be generated by unitary processes (for which post-selection is no exception). (ii) From a purely physical point of view, measurements are not 'outside' of quantum mechanics. (iii) The only difference between the abilities of measurement-based protocols and unitary circuits for quantum computing comes from practical (technology dependent) constraints. We emphasise the importance of distinguishing between differences that are (i) fundamental but without physical import; (ii) fundamental and possess physical import; and (iii) are not fundamental but have practical import. We also emphasise the importance of separating theoretical and experimental elements of measurement, primarily projection and amplification, which are physically very different. Note that since we are concerned with facts regarding physical processes, this article has little if anything to do with interpretations of quantum mechanics.