The on-demand generation of pure quantum excitations is important for the operation of quantum systems, but it is particularly difficult for a system of fermions. This is because any perturbation ...affects all states below the Fermi energy, resulting in a complex superposition of particle and hole excitations. However, it was predicted nearly 20 years ago that a Lorentzian time-dependent potential with quantized flux generates a minimal excitation with only one particle and no hole. Here we report that such quasiparticles (hereafter termed levitons) can be generated on demand in a conductor by applying voltage pulses to a contact. Partitioning the excitations with an electronic beam splitter generates a current noise that we use to measure their number. Minimal-excitation states are observed for Lorentzian pulses, whereas for other pulse shapes there are significant contributions from holes. Further identification of levitons is provided in the energy domain with shot-noise spectroscopy, and in the time domain with electronic Hong-Ou-Mandel noise correlations. The latter, obtained by colliding synchronized levitons on a beam splitter, exemplifies the potential use of levitons for quantum information: using linear electron quantum optics in ballistic conductors, it is possible to imagine flying-qubit operation in which the Fermi statistics are exploited to entangle synchronized electrons emitted by distinct sources. Compared with electron sources based on quantum dots, the generation of levitons does not require delicate nanolithography, considerably simplifying the circuitry for scalability. Levitons are not limited to carrying a single charge, and so in a broader context n-particle levitons could find application in the study of full electron counting statistics. But they can also carry a fraction of charge if they are implemented in Luttinger liquids or in fractional quantum Hall edge channels; this allows the study of Abelian and non-Abelian quasiparticles in the time domain. Finally, the generation technique could be applied to cold atomic gases, leading to the possibility of atomic levitons.
The on-demand emission of coherent and indistinguishable electrons by independent synchronized sources is a challenging task of quantum electronics, in particular regarding its application for ...quantum information processing. Using two independent on-demand electron sources, we triggered the emission of two single-electron wave packets at different inputs of an electronic beam splitter. Whereas classical particles would be randomly partitioned by the splitter, we observed two-particle interference resulting from quantum exchange. Both electrons, emitted in indistinguishable wave packets with synchronized arrival time on the splitter, exited in different outputs as recorded by the low-frequency current noise. The demonstration of two-electron interference provides the possibility of manipulating coherent and indistinguishable single-electron wave packets in quantum conductors.
Background and purpose
We previously reported that certain optical coherence tomography (OCT) measures were sensitive and reliable in identifying idiopathic intracranial hypertension (IIH). This ...prospective study aimed to define OCT measures that allow differentiation of IIH with and without papilledema, thereby helping clinical decision‐making.
Methods
Eight patients with IIH with papilledema, nine without papilledema and 19 with other neurological diseases were included. OCT measures were obtained before lumbar puncture and within 2 h, 1, 3 and 6 months after lumbar puncture with cerebrospinal fluid (CSF) removal.
Results
All patients with papilledema had increased retinal nerve fiber layer (RNFL) thickness and elevated CSF pressure. All patients without papilledema had normal RNFL but elevated CSF pressure. After CSF removal, reduced RNFL thickness was registered in all eight patients with IIH with papilledema. No significant change in RNFL thickness after CSF removal was observed in IIH without papilledema or in patients with other neurological diseases, although reduced CSF pressure was documented. RNFL thickness tended to be normal in patients with IIH with papilledema at 3–6 months after CSF removal. All patients with IIH showed increased rim area and rim thickness, but reduced optic cup volume regardless of RNFL thickness or papilledema.
Conclusions
Retinal nerve fiber layer thickness is sensitive for monitoring acute IIH and evaluating treatment effect. Increased rim area and rim thickness and decreased optic cup volume are reliable parameters that indicate persistently increased CSF pressure and risk of relapse. OCT measures are sensitive and reliable for diagnosing subtle IIH even in the absence of papilledema.
This work reports a holistic experimental investigation of stimulated Brillouin scattering (SBS) features and electron temperature inversion near the third electron gyroharmonic 3fce using the ...European Incoherent Scatter (EISCAT) heating facility. The evolution of SBS features including spectral offset, width, and power varies asymmetrically near 3fce. The asymmetries among SBS, electron temperature, and high frequency‐enhanced ion lines are clearly exhibited for pumping above f0 ≥ 3fce. Electron temperature Te at the resonance regime has been retrieved from the measured SBS spectra based on the wave matching theory. The inversion results by SBS are consistent with measurement by the EISCAT UHF incoherent scatter radar (ISR) at the resonance altitude. The comparison of electron temperature Te and ion temperature Ti between SBS and ISR enlightens great potentials for developing realistic ionospheric diagnostic technique.
Key Points
Clearly, SBS dynamics and spectral features are characterized near third electron gyroharmonics at EISCAT
Qualitative comparison of electron temperature inversion based on SBS agrees with ISR measurement
The asymmetries of SBS and DM are closely correlated with enhanced ion lines and electron temperature near 3fce
The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, ...located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the "roof of the world" and the antiquity of human high-altitude occupations more generally.
Mesenchymal stem cells, under spatiotemporal regulation of genes and microenvironment, are capable of spontaneously aggregating into dense regions, a phenomenon known as mesenchymal condensation. ...Mesenchymal condensation is an evolutionarily conserved developmental event that is critical in initiating morphogenesis of teeth and systemic organs. Mesenchymal stem cells hold the intrinsic ability to self-assemble in culture, and the generation of stem cell aggregates based on this property that mimics developmental mesenchymal condensation has become a potent and promising approach in regenerative medicine. This review discusses the mesenchymal condensation principles and its role as well as mechanism in tooth morphogenesis, as well as the engineering strategies for constructing mesenchymal stem cell aggregates and their application experience in tooth regeneration. It aims to start from the perspective of "development-inspired regeneration" and provide insights into understanding stem cell developmental biology
The Mayo Clinical Score is used in clinical trials to describe the clinical status of patients with ulcerative colitis (UC). It comprises four subscores: rectal bleeding (RB), stool frequency (SF), ...physician's global assessment, and endoscopy (ENDO). According to recent US Food and Drug Administration guidelines (Ulcerative colitis: developing drugs for treatment, Guidance Document, https://www.fda.gov/regulatory-information/s. 2022), clinical response and remission should be based on modified Mayo Score (mMS) relying on RB, SF, and ENDO. Typically, ENDO is performed at the beginning and end of each phase, whereas RB and SF are more frequently available. Item response theory (IRT) models allow the shared information to be used for prediction of all subscores at each observation time; therefore, it leverages information from RB and SF to predict ENDO. A UC disease IRT model was developed based on four etrolizumab phase III studies to describe the longitudinal mMS subscores, placebo response, and remission at the end of induction and maintenance. For each subscore, a bounded integer model was developed. The placebo response was characterized by a mono-exponential function acting on all mMS subscores similarly. The final model reliably predicted longitudinal mMS data. In addition, remission was well-predicted by the model, with only 5% overprediction at the end of induction and 3% underprediction at the end of maintenance. External evaluation of the final model using placebo arms from five different studies indicated adequate performance for both longitudinal mMS subscores and remission status. These results suggest utility of the current disease model for informed decision making in UC clinical development, such as assisting future clinical trial designs and evaluations.
Multi-spheres and Superquadrics are popular approaches for addressing particle shape effect in the Discrete Element Method (DEM). This study focuses on the mechanical characteristics of cubical ...particles, modeled by the two methods (using EDEM and LIGGGHTS), through conducting a series of numerical case studies at both single particle and bulk levels. In the first part of the study, several testing scenarios, which clarify the impact, interlocking, sliding and tilting characteristics of the particle, are discussed and the respective simulations are carried out. The results emphasize the importance of surface bumpiness and edge sharpness in the single-particle behaviour and are used for informing the bulk response.
Further, role of the two shape descriptors on bulk response is evaluated in angle of repose, Jenike shear and silo flow simulations. The results of these tests are assessed both at the micro, directly through DEM outputs, and at the meso- and macro-scales, using a coarse graining technique. It is seen that the properties of edge and surface in superquadric and multi-sphere particles considerably influence the heap profile in the angle of repose test. However, in a Jenike direct shear, the shape complexity only significantly affects the shear strength, porosity and mode of motion when the packing is dense. Additionally, in silo discharge, the effect of shape features is even less on the flow pattern and mass flow rate but is found to have a significant influence on the stress distribution.
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•Edge sharpness, for superquadric, and surface bumpiness, for multi-sphere, is studied.•Shape complexity greatly influences single particle behaviour.•Density controls the influence of shape characteristics on shearing response of cubes.•Shape factor influences stresses inside silo, while flow kinematics are unaffected.•Superquadrics and multi-spheres are compared in terms of computational efficiency.
There is a need for new approaches and endpoints in oncology drug development, particularly with the advent of immunotherapies and the multiple drug combinations under investigation. Tumor dynamics ...modeling, a key component to oncology "model-informed drug development," has shown a growing number of applications and a broader adoption by drug developers and regulatory agencies in the past years to support drug development and approval in a variety of ways. Tumor dynamics modeling is also being investigated in personalized cancer therapy approaches. These models and applications are reviewed and discussed, as well as the limitations and issues open for further investigations. A close collaboration between stakeholders like clinical investigators, statisticians, and pharmacometricians is warranted to advance clinical cancer therapeutics.
Model‐based tumor growth inhibition (TGI) metrics are increasingly used to predict overall survival (OS) data in Phase III immunotherapy clinical trials. However, there is still a lack of ...understanding regarding the differences between two‐stage or joint modeling methods to leverage Phase I/II trial data and help early decision‐making. A recent study showed that TGI metrics such as the tumor growth rate constant KG may have good operating characteristics as early endpoints. This previous study used a two‐stage approach that is easy to implement and intuitive but prone to bias as it does not account for the relationship between the longitudinal and time‐to‐event processes. A relevant alternative is to use a joint modeling approach. In the present article, we evaluated the operating characteristics of TGI metrics using joint modeling, assuming an OS model previously developed using historical data. To that end, we used TGI and OS data from IMpower150—a study investigating atezolizumab in over 750 patients suffering from non‐small cell lung cancer—to mimic randomized Phase Ib/II trials varying in terms of number of patients included (40 to 15 patients per arm) and follow‐up duration (24 to 6 weeks after the last patient included). In this context, joint modeling did not outperform the two‐stage approach and provided similar operating characteristics in all the investigated scenarios. Our results suggest that KG geometric mean ratio could be used to support early decision‐making provided that 30 or more patients per arm are included and followed for at least 12 weeks.
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