Non-Gaussian quantum state generation by multi-photon subtraction at the telecommunication wavelength.

In the field of continuous-variable quantum information processing, non-Gaussian states with negative values of the Wigner function are crucial for the development of a fault-tolerant universal quantum computer. While several non-Gaussian states have been generated experimentally, none have been created using ultrashort optical wave packets, which are necessary for high-speed quantum computation, in the telecommunication wavelength band where mature optical communication technology is available. In this paper, we present the generation of non-Gaussian states on wave packets with a short 8-ps duration in the 1545.32 nm telecommunication wavelength band using photon subtraction up to three photons. We used a low-loss, quasi-single spatial mode waveguide optical parametric amplifier, a superconducting transition edge sensor, and a phase-locked pulsed homodyne measurement system to observe negative values of the Wigner function without loss correction up to three-photon subtraction. These results can be extended to the generation of more complicated non-Gaussian states and are a key technology in the pursuit of high-speed optical quantum computation.

Generation of highly pure single-photon state at telecommunication wavelength.

Telecommunication wavelength with well-developed optical communication technologies and low losses in the waveguide are advantageous for quantum applications. However, an experimental generation of non-classical states called non-Gaussian states at the telecommunication wavelength is still underdeveloped. Here, we generate highly-pure-single-photon states, one of the most primitive non-Gaussian states, by using a heralding scheme with an optical parametric oscillator and a superconducting nano-strip photon detector. The Wigner negativity, the indicator of non-classicality, of the generated single photon state is -0.228 ± 0.004, corresponded to 85.1 ± 0.7% of single photon and the best record of the minimum value at all wavelengths. The quantum-optics-technology we establish can be easily applied to the generation of various types of quantum states, opening up the possibility of continuous-variable-quantum-information processing at the telecommunication wavelength.

Generation of Schrödinger cat states with Wigner negativity using a continuous-wave low-loss waveguide optical parametric amplifier.

Continuous-wave (CW) squeezed light is used in the generation of various optical quantum states, and thus is a fundamental resource of fault-tolerant universal quantum computation using optical continuous variables. To realize a practical quantum computer, a waveguide optical parametric amplifier (OPA) is an attractive CW squeezed light source in terms of its THz-order bandwidth and suitability for modularization. The usages of a waveguide OPA in quantum applications thus far, however, are limited due to the difficulty of the generation of the squeezed light with a high purity. In this paper, we report the first observation of Wigner negativity of the states generated by a heralding method using a waveguide OPA. We generate Schrödinger cat states at the wavelength of 1545 nm with Wigner negativity using a quasi-single-mode ZnO-doped periodically poled LiNbO3 waveguide module we developed. Wigner negativity is regarded as an important indicator of the usefulness of the quantum states as it is essential in the fault-tolerant universal quantum computation. Our result shows that our waveguide OPA can be used in wide range of quantum applications leading to a THz-clock optical quantum computer.

Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 µg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

A refined method of en bloc open-door laminoplasty for resection of intradural spinal tumors in the thoracic and lumbar spine.

BACKGROUND: The open-door laminoplasty has been used to treat cervical spondylotic myelopathy. This technique has been applied to the surgical treatment of thoracic and lumbar spinal canal tumors instead of simple laminectomy or hemilaminectomy. However, previously reported laminoplasty methods did not keep posterior supporting elements intact such as the laminae and the spinous processes with supraspinous and interspinous ligaments, and almost all of them needed instruments for the fixation of reconstructed laminae. The purpose of this paper is to introduce our open-door laminoplasty method, which keep all posterior supporting elements intact and reconstruct the laminae without instrument. METHODS: Eight patients (mean age 61 years) underwent en bloc open-door laminoplasty in the thoracic and lumbar spine for resection of intradural spinal tumors. Two grooves are made bilaterally on the laminae just medial side of the facet joints. One-half of each spinous process of the adjacent vertebrae above and below the laminoplasty is cracked diagonally to create a green stick fracture and bent to the hinged side for sufficient elevation of the laminar flap. After tumor resection, the laminar flap is restored to its original site, resulting in the complete preservation of the posterior supporting elements. RESULTS: Operative exposure was good and permitted complete resection. No complications such as postoperative spinal canal stenosis or kyphosis were observed. Computed tomography(CT) indicated that bony fusion occurred in all cases. CONCLUSION: The supraspinous and interspinous ligaments above and below laminoplasty were kept intact during surgery in our method. Therefore, the continuity of posterior supporting elements (laminae and spinous processes connected by supraspinous and interspinous ligaments) were completely preserved.

Logical states for fault-tolerant quantum computation with propagating light.

To harness the potential of a quantum computer, quantum information must be protected against error by encoding it into a logical state that is suitable for quantum error correction. The Gottesman-Kitaev-Preskill (GKP) qubit is a promising candidate because the required multiqubit operations are readily available at optical frequency. To date, however, GKP qubits have been demonstrated only at mechanical and microwave frequencies. We realized a GKP state in propagating light at telecommunication wavelength and verified it through homodyne measurements without loss corrections. The generation is based on interference of cat states, followed by homodyne measurements. Our final states exhibit nonclassicality and non-Gaussianity, including the trident shape of faint instances of GKP states. Improvements toward brighter, multipeaked GKP qubits will be the basis for quantum computation with light.

Nonlinear feedforward enabling quantum computation.

Measurement-based quantum computation with optical time-domain multiplexing is a promising method to realize a quantum computer from the viewpoint of scalability. Fault tolerance and universality are also realizable by preparing appropriate resource quantum states and electro-optical feedforward that is altered based on measurement results. While linear feedforward has been realized and become a common experimental technique, nonlinear feedforward was unrealized until now. In this paper, we demonstrate that a fast and flexible nonlinear feedforward realizes the essential measurement required for fault-tolerant and universal quantum computation. Using non-Gaussian ancillary states, we observed 10% reduction of the measurement excess noise relative to classical vacuum ancilla.

Quantum arbitrary waveform generator.

Controlling the temporal waveform of light is the key to a versatile light source in classical and quantum electronics. Although pulse shaping of classical light is mature and has been used in various fields, more advanced applications would be realized by a light source that generates arbitrary quantum light with arbitrary temporal waveforms. We call such a device a quantum arbitrary waveform generator (Q-AWG). The Q-AWG must be able to handle various quantum states of light, which are fragile. Thus, the Q-AWG requires a radically different methodology from classical pulse shaping. Here, we invent an architecture of Q-AWGs that can operate semi-deterministically at a repetition rate over gigahertz in principle. We demonstrate its core technology via generating highly nonclassical states with temporal waveforms that have never been realized before. This result would lead to powerful quantum technologies based on Q-AWGs such as practical optical quantum computing.

Programmable and sequential Gaussian gates in a loop-based single-mode photonic quantum processor.

A quantum processor to import, process, and export optical quantum states is a common core technology enabling various photonic quantum information processing. However, there has been no photonic processor that is simultaneously universal, scalable, and programmable. Here, we report on an original loop-based single-mode versatile photonic quantum processor that is designed to be universal, scalable, and programmable. Our processor can perform arbitrarily many steps of programmable quantum operations on a given single-mode optical quantum state by time-domain processing in a dynamically controlled loop-based optical circuit. We use this processor to demonstrate programmable single-mode Gaussian gates and multistep squeezing gates. In addition, we prove that the processor can perform universal quantum operations by injecting appropriate ancillary states and also be straightforwardly extended to a multimode processor. These results show that our processor is programmable, scalable, and potentially universal, leading to be suitable for general-purpose applications.

Predominant role of T cell receptor (TCR)-alpha chain in forming preimmune TCR repertoire revealed by clonal TCR reconstitution system.

The CDR3 regions of T cell receptor (TCR)-alpha and -beta chains play central roles in the recognition of antigen (Ag)-MHC complex. TCR repertoire is created on the basis of Ag recognition specificity by CDR3s. To analyze the potential spectrum of TCR-alpha and -beta to exhibit Ag specificity and generate TCR repertoire, we established hundreds of TCR transfectants bearing a single TCR-alpha or -beta chain derived from a cytotoxic T cell (CTL) clone, RT-1, specific for HIVgp160 peptide, and randomly picked up TCR-beta or -alpha chains. Surprisingly, one-third of such TCR-beta containing random CDR3 beta from naive T cells of normal mice could reconstitute the antigen-reactive TCR coupling with RT-1 TCR-alpha. A similar dominant function of TCR-alpha in forming Ag-specific TCR, though low-frequency, was obtained for lymphocytic choriomeningitis virus-specific TCR. Subsequently, we generated TCR-alpha and/or -beta transgenic (Tg) mice specific for HIVgp160 peptide, and analyzed the TCR repertoire of Ag-specific CTLs. Similar to the results from TCR reconstitution, TCR-alpha Tg generated CTLs with heterogeneous TCR-beta, whereas TCR-beta Tg-induced CTLs bearing a single TCR-alpha. These findings of Ag recognition with minimum involvement of CDR3 beta expand our understanding regarding the flexibility of the spectrum of TCR and suggest a predominant role of TCR-alpha chain in determining the preimmune repertoire of Ag-specific TCR.

On-demand photonic entanglement synthesizer.

Quantum information protocols require various types of entanglement, such as Einstein-Podolsky-Rosen, Greenberger-Horne-Zeilinger, and cluster states. In optics, on-demand preparation of these states has been realized by squeezed light sources, but such experiments require different optical circuits for different entangled states, thus lacking versatility. Here, we demonstrate an on-demand entanglement synthesizer that programmably generates all these entangled states from a single squeezed light source. This is achieved by a loop-based circuit that is dynamically controllable at nanosecond time scales and processes optical pulses in the time domain. We verify the generation of five different small-scale entangled states and a large-scale cluster state containing more than 1000 modes without changing the optical circuit. Moreover, this circuit enables storage and release of one part of the generated entangled state, thus working as a quantum memory. Our demonstration should open a way for a more general entanglement synthesizer and a scalable quantum processor.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. METHODS AND ANALYSIS: The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). ETHICS AND DISSEMINATION: The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. TRIAL REGISTRATION NUMBER: UMIN000018752.

Simultaneous anterior and posterior screw fixations confined to the axis for stabilization of a 3-part fracture of the axis (odontoid, dens, and hangman fractures): report of 2 cases.

Fractures of the axis are considered to be one of the most common injuries to the cervical spine, accounting for more than 20% of all cervical spine fractures. Multiple fractures of the axis are much rarer, accounting for 1% of all cervical fractures. Management of such complex fractures is still challenging, and there is no strong consensus for the treatment. The authors describe the cases of 2 patients who presented with 3-part fractures of the axis consisting of an odontoid Type II fracture and a Levine-Edwards Type IA fracture, which were treated with concurrent insertion of an anterior odontoid screw and bilateral posterior pedicle screws. The cases presented were characterized by 1) a Type II odontoid fracture; 2) a Type IA traumatic spondylolisthesis with no or a little translation and angulation of C-2 on C-3 in a ring fracture of the axis; and 3) no disorders at the C2-3 disc on MR images. Therefore, the authors performed surgery confined to the axis by concurrently inserting an anterior odontoid screw and posterior bilateral pedicle screws without arthrodesis of C2-3. This was followed with cervical soft collar fixation for only 1-2 weeks. The outcomes were favorable, including good osteosynthesis, high primary stability, early patient mobilization, and preserved range of motion of the cervical spine at C2-3 as well as at C1-2.

CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is constitutively expressed on CD25(+)CD4(+) regulatory T cells (Treg) and is suggested to play a role in Treg-mediated suppression. However, the results of analysis with anti-CTLA-4 have been controversial. We addressed this issue by analyzing mice over-expressing or deficient in CTLA-4. For over-expression, CTLA-4 transgenic mice expressing a full-length (FL) or a truncated (TL) mutant of CTLA-4 were analyzed. FL T cells expressed similar levels of CTLA-4 to Treg, whereas TL T cells expressed much higher levels on the cell surface. The number of Treg in both mice was decreased, although Foxp3 expression was not altered. Treg from both mice exerted suppressive activity, whereas CD25(-) T cells from FL mice showed no suppression. Furthermore, CD25(+)CD4 thymocytes from young CTLA-4-deficient mice were analyzed and found to exhibit suppressive activity. These results indicate that Treg exert in vitro suppressive activity independent of CTLA-4 expression.

In vivo overexpression of CTLA-4 suppresses lymphoproliferative diseases and thymic negative selection.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) induces major inhibitory signals for T cell activation. From analyses of TCR-transgenic (Tg) CTLA-4-deficient mice, it has been believed that CTLA-4 does not affect thymocyte development. To focus upon the in vivo function of CTLA-4 in thymocyte development from a different aspect, we have established Tg mice expressing either full-length CTLA-4 (FL-Tg) or a mutant CTLA-4 lacking the cytoplasmic region (truncated, TR-Tg), and analyzed thymocyte development. TR-T cells express much higher CTLA-4 on the cell surface than FL-T cells, in which most CTLA-4 was localized in intracellular vesicles. While CTLA-4-/- mice exhibit lymphoproliferative disease, neither of the Tg mice with CTLA-4-/- background developed the disorder. Although the development of thymocytes appeared normal in both Tg mice, in vivo depletion of double-positive thymocytes by injection of anti-CD3 Ab as well as the elimination of minor lymphocyte-stimulating antigen-reactive thymocytes were impaired in FL-Tg mice but not in TR-Tg mice. Functionally, cross-linking of CTLA-4 on thymocytes from FL-Tg mice, but not from TR-Tg mice, inhibited proliferation. These results reveal a potential role of CTLA-4, through its cytoplasmic domain, in the negative selection of thymocytes and in the prevention of lymphoproliferative disease.