Dissipation-Based Quantum Sensing of Magnons with a Superconducting Qubit.

Hybrid quantum devices expand the tools and techniques available for quantum sensing in various fields. Here, we experimentally demonstrate quantum sensing of a steady-state magnon population in a magnetostatic mode of a ferrimagnetic crystal. Dispersively coupling the magnetostatic mode to a superconducting qubit allows for the detection of magnons using Ramsey interferometry with a sensitivity on the order of 10^{-3} magnons/sqrt[Hz]. The protocol is based on dissipation as dephasing via fluctuations in the magnetostatic mode reduces the qubit coherence proportionally to the number of magnons.

Early detection of Niemann-pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat.

STUDY OBJECTIVES: Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings. METHODS: Ten patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients. RESULTS: Six NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels. DISCUSSION: Our study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients' NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients. CONCLUSION: The NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.

Breaking the trade-off between fast control and long lifetime of a superconducting qubit.

The rapid development in designs and fabrication techniques of superconducting qubits has made coherence times of qubits longer. In the future, however, the radiative decay of a qubit into its control line will be a fundamental limitation, imposing a trade-off between fast control and long lifetime of the qubit. Here, we break this trade-off by strongly coupling another superconducting qubit along the control line. This second qubit, which we call "Josephson quantum filter" (JQF), prevents the first qubit from emitting microwave photons and thus suppresses its relaxation, while transmitting large-amplitude control microwave pulses due to the saturation of the quantum filter, enabling fast qubit control. This device functions as an automatic decoupler between a qubit and its control line and could help in the realization of a large-scale superconducting quantum processor by reducing the heating of the qubit environment and the crosstalk between qubits.

Helicity-Changing Brillouin Light Scattering by Magnons in a Ferromagnetic Crystal.

Brillouin light scattering in ferromagnetic materials usually involves one magnon and two photons and their total angular momentum is conserved. Here, we experimentally demonstrate the presence of a helicity-changing two-magnon Brillouin light scattering in a ferromagnetic crystal, which can be viewed as a four-wave mixing process involving two magnons and two photons. Moreover, we observe an unconventional helicity-changing one-magnon Brillouin light scattering, which apparently infringes the conservation law of the angular momentum. We show that the crystal angular momentum intervenes to compensate the missing angular momentum in the latter scattering process.

Brillouin Light Scattering by Magnetic Quasivortices in Cavity Optomagnonics.

A ferromagnetic sphere can support optical vortices in the form of whispering gallery modes and magnetic quasivortices in the form of magnetostatic modes with nontrivial spin textures. These vortices can be characterized by their orbital angular momenta. We experimentally investigate Brillouin scattering of photons in the whispering gallery modes by magnons in the magnetostatic modes, zeroing in on the exchange of the orbital angular momenta between the optical vortices and magnetic quasivortices. We find that the conservation of the orbital angular momentum results in different nonreciprocal behavior in the Brillouin light scattering. New avenues for chiral optics and optospintronics can be opened up by taking the orbital angular momenta as a new degree of freedom for cavity optomagnonics.

Information-to-work conversion by Maxwell's demon in a superconducting circuit quantum electrodynamical system.

Information thermodynamics bridges information theory and statistical physics by connecting information content and entropy production through measurement and feedback control. Maxwell's demon is a hypothetical character that uses information about a system to reduce its entropy. Here we realize a Maxwell's demon acting on a superconducting quantum circuit. We implement quantum non-demolition projective measurement and feedback operation of a qubit and verify the generalized integral fluctuation theorem. We also evaluate the conversion efficiency from information gain to work in the feedback protocol. Our experiment constitutes a step toward experimental studies of quantum information thermodynamics in artificially made quantum machines.

Cavity Optomagnonics with Spin-Orbit Coupled Photons.

We experimentally implement a system of cavity optomagnonics, where a sphere of ferromagnetic material supports whispering gallery modes (WGMs) for photons and the magnetostatic mode for magnons. We observe pronounced nonreciprocity and asymmetry in the sideband signals generated by the magnon-induced Brillouin scattering of light. The spin-orbit coupled nature of the WGM photons, their geometrical birefringence, and the time-reversal symmetry breaking in the magnon dynamics impose the angular-momentum selection rules in the scattering process and account for the observed phenomena. The unique features of the system may find interesting applications at the crossroad between quantum optics and spintronics.

Itinerant electron magnetism in CaRu(1-x)Mn(x)O(3) (0 ≤ x ≤ 0.5).

The effect of Mn substitution in paramagnetic metal CaRuO(3) was studied by magnetization and neutron diffraction measurements. Development of ferromagnetic order is observed for x≥0.2 in CaRu(1-x)Mn(x)O(3). For the sample with x = 0.4, the Curie temperature of ∼160 K is obtained from the Arrott plot and the ratio of effective moment and saturation moment P(eff)/M(0) is estimated to be ∼4.8. We further found that the magnetization is significantly suppressed with decreasing temperature T below ∼90 K. In the neutron diffraction experiment at T = 15 K, we observed the evolution of a magnetic Bragg peak originating from the G-type antiferromagnetic order as well as the ferromagnetic one. This strongly suggests that both ferromagnetic and antiferromagnetic states are coexistent with each other at low temperatures. In the M(T)(0)(2) against T(2) plot (here, M(T)(0) is a spontaneous magnetization estimated from the Arrott plot), M(T)(0)(2) linearly increases with decreasing T(2) in the ferromagnetic region between ∼90 and 160 K. The ferromagnetic properties of the CaRu(1-x)Mn(x)O(3) system (x≤0.5) are well explained in terms of spin fluctuation theory based on the itinerant electron model rather than the localized spin model.

Zoledronate facilitates large-scale ex vivo expansion of functional gammadelta T cells from cancer patients for use in adoptive immunotherapy.

BACKGROUND: Human gammadelta T cells can be activated by phospho-antigens and aminobisphosphonates such as zoledronate. Because they can kill tumor cells in a major histocompatibility complex (MHC)-unrestricted manner, adoptive transfer of activated gammadelta T cells may represent a novel cancer immunotherapy. We tested whether gammadelta T cells from advanced cancer patients can be expanded by zoledronate. METHODS: Peripheral blood mononuclear cells from healthy donors and patients with advanced non-small cell lung cancer, bone metastatic breast or prostate cancer, or lung metastatic colorectal cancer, were stimulated with zoledronate (5 microM) and interleukin (IL)-2 (1000 IU/mL) for 14 days. The phenotype and function of the expanded gammadelta T-cell populations from healthy donors and cancer patients were compared. RESULTS: Gammadelta T cells from cancer patients and healthy donors responded to zoledronate equally well in terms of both phenotype and function. gammadelta T cells grew rapidly in vitro and expression of effector molecules, such as interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, perforin, granzyme B, FasL and TRAIL, increased over time. Cytotoxicity peaked on days 12-14, and proliferation continued up to 14 days, during which time>1x10(9) gammadelta T cells could be obtained from a starting sample of 45-70 mL peripheral blood. DISCUSSION: Using the agent zoledronate, already widely used in the clinic, we have established that efficient large-scale ex vivo expansion of gammadelta T cells from cancer patients is possible. These cells exert potent cytotoxicity and may be used for autologous cellular immunotherapy of cancer.

Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses.

Glycosaminoglycans are accumulated in both mucopolysaccharidoses (MPS) and mucolipidoses (ML). MPS I, II, III and VII and ML II and ML III patients cannot properly degrade heparan sulphate (HS). In spite of the importance of HS storage in the metabolic pathway in these diseases, blood and urine HS levels have not been determined systematically using a simple and economical method. Using a new ELISA method using anti-HS antibodies, HS concentrations in blood and urine were determined in MPS and ML II and ML III patients. HS concentrations were determined in 156 plasma samples from MPS I (n = 23), MPS II (n = 26), MPS III (n = 24), MPS IV (n = 62), MPS VI (n = 5), MPS VII (n = 5), ML II (n = 8) and ML III (n = 3), and 205 urine samples from MPS I (n = 33), MPS II (n = 33), MPS III (n = 30), MPS IV (n = 82), MPS VI (n = 7), MPS VII (n = 9), ML II (n = 8) and ML III (n = 3). The ELISA method used monoclonal antibodies against HS. MPS I, II, III and VII and ML II and III patients had significant elevation in plasma HS, compared to the age-matched controls (p < 0.0001). Eighty-three out of 89 (93.3%) of individual values in the above MPS types and ML were above the mean +2SD of the controls. In urine samples, 75% of individual values in patients with those types were above the mean +2SD of the controls. In contrast to the previous understanding of the HS metabolic pathway, plasma HS levels in all five MPS VI and 15% of MPS IV patients were elevated above the mean +2SD of the controls. These findings suggest that HS concentration determined by ELISA, especially in plasma, could be a helpful marker for detection of the most severe MPS I, II, III, VI and VII and ML II, distinguishing them from normal populations.

Keratan sulphate levels in mucopolysaccharidoses and mucolipidoses.

The mucopolysaccharidoses (MPS) is characterized by accumulation of glycosaminoglycans (GAGs), and mucolipidosis (ML) by accumulation of GAGs and sphingolipids. Each type of MPS accumulates specific GAGs. The lysosomal enzymes N-acetylgalactosamine-6-sulphate sulphatase and beta-galactosidase involve the stepwise degradation of keratan sulphate (KS). Deficiency of these enzymes results in elevation of KS levels in the body fluids and in tissues, leading to MPS IV disease. In this study, we evaluated blood and urine KS levels in types of MPS and ML other than MPS IV. Eighty-five plasma samples came from MPS I (n = 18), MPS II (n = 28), MPS III (n = 20), MPS VI (n = 3), MPS VII (n = 5) and ML (n = 11) patients while 127 urine samples came from MPS I (n = 34), MPS II (n = 34), MPS III (n = 32), MPS VI (n = 7), MPS VII (n = 9) and ML (n = 11) patients. KS levels were determined using the ELISA method. Plasma KS levels varied with age in both control and patient populations. In all age groups, the mean values of plasma KS in MPS and ML patients were significantly higher than those in the age-matched controls. Plasma KS values in four newborn patients were above the mean + 2SD of the age-matched controls (mean, 41 ng/ml). Overall, 85.9% of individual values in non-type IV MPS and ML patients were above the mean + 2SD of the age-matched controls. For urine KS levels, 24.4% of individual values in patients were above the mean + 2SD of the age-matched controls. In conclusion, KS in blood is elevated in each type of non-type IV MPS examined, in contrast to the conventional understanding. This finding suggests that measurement of KS level provides a new diagnostic biomarker in a wide variety of mucopolysaccharidoses and mucolipidoses in addition to MPS IV.

Confocal and probe microscopy to study gene transfection mediated by cationic liposomes with a cationic cholesterol derivative.

A novel cationic cholesterol derivative with a hydroxyethyl amino head group (I) has been synthesized and used for liposome-mediated gene transfection. Cationic liposomes with derivative (I) greatly facilitated gene transfection into various cultured cells. The efficiency of transfection by liposomes with derivative (I) was much higher than that using liposomes with DC-chol (II) or lipofectine. Atomic force microscopy and confocal laser scanning microscopy revealed the molecular mechanism of gene transfection by cationic liposomes. The results showed that at least two steps were involved in gene transfection mediated by cationic liposomes. One was endocytosis, where the liposome-DNA complex was internalized into target cells, and the other was membrane fusion between the liposome vectors and endosomes, where DNA transferred from the liposome to the nucleus. In addition we found that microtubules were involved in the intracellular dynamics of gene transfection.

Inhibitory effects of sodium butyrate on proliferation and invasiveness of human glioma cells.

OBJECTIVE: Sodium butyrate (SB), a differentiation-inducing agent, has been demonstrated to inhibit cellular proliferation in a number of human cell lines. Its precise mechanisms remain to be clarified, however. We investigated molecular mechanisms of SB-induced growth suppression as well as the effects of SB on the invasiveness of human glioma cells. METHODS: Human glioma U87MG and U251MG cells were treated with 1 or 2 mmol/L SB for 48 hours, and the inhibition of cell growth was assessed by spectrophotometric analysis. Cell cycle analysis was carried out by the 5-bromo-2'-deoxyuridine incorporation method, and expression of cell cycle-regulatory proteins was determined by immunoblotting. In addition, invasiveness was assessed using a Transwell chamber (Iwaki, Tokyo, Japan) with extracellular matrix substrate fibronectin or laminin (Iwaki). RESULTS: SB treatment resulted in significantly suppressed proliferation of both U87MG and U251MG cells in a dose-dependent manner. It inhibited the G1-S transition, which was associated with increased expression of p21 and cyclin D1 and reduced pRb phosphorylation. Treatment with antisense oligonucleotide for Rb abrogated SB-induced G1 arrest. p21 up-regulation was independent of the p53 status of the glioma cells. SB treatment also inhibited invasiveness on fibronectin and laminin. CONCLUSION: Our results indicate that SB may suppress the growth of human glioma cells through modulation of cell cycle progression and also may affect their invasiveness on extracellular matrix substrates, which suggests that SB may be a useful therapeutic agent in treating multiple aspects of malignant gliomas.

[Primary squamous cell carcinoma of the prostate forming a rectourethral fistula: a case report].

Eleven cases of squamous cell carcinoma of the prostate have been previously reported in the Japanese medical literature. Patients with this type of carcinoma have dismal prognoses. Herein, we report a case in a 61-year-old man who was admitted to our hospital and whose chief complaints were dysuria and high fever. Pyuria, bacteriuria, and the results of a digital rectal examination suggested acute prostatitis. Despite the administration of antibiotics, the dysuria did not improve. A transrectal needle biopsy was performed, and histology of the tissue showed squamous cell carcinoma. After chemotherapy using methotrexate, pirarubicin, and cisplatin, total pelvic excentration was performed. At 12 months after the operation, the patient is alive with no evidence of the disease.

Sustained release of basic fibroblast growth factor and angiogenesis in a novel covalently crosslinked gel of heparin and alginate.

The construction of organs by tissue engineering and regenerative engineering, using an artificial extracellular matrix, is an innovative method that is expected to replace artificial organs and organ transplantation. We have produced an artificial extracellular matrix of alginate and demonstrated that the matrix stimulated the regeneration of skin, nerve, and bone. In this report, the new matrix, which consists of heparin and alginate covalently crosslinked with ethylenediamine, was produced to stabilize and control the release of growth factors. Heparin content of the new matrix was confirmed by toluidine blue absorption, elementary analysis, and Fourier transform infrared spectrum. In vitro experiments showed that the new matrix significantly suppressed the initial burst of basic fibroblast growth factor, which is a representative member of heparin-binding growth factors, and released biologically active basic fibroblast growth factor for 1 month under physiological conditions. Obvious cellular infiltration and angiogenesis were shown to occur in the new matrix which was implanted subcutaneously in the dorsal area of rat with 1 microg of basic fibroblast growth factor for 2 weeks. This new matrix may be useful for not only the construction of transplantable blood vessels of small diameter, but also the induction of angiogenesis in regenerated skin constructed by tissue engineering.

Effects of chlorpropham (CIPC) on the hemopoietic system of rats.

Male F344 rats were given 0 or 3% chlorpropham in the diet and at 2, 4, 6, 8 or 13 weeks of administration, five rats in each group were examined for hematology, plasma clinical chemistry and pathology. Marked splenomegaly and hepatomegaly were observed in treated rats at 2-13 weeks of administration. Red blood cell counts, hemoglobin concentration, packed cell volume and platelet counts were significantly decreased and methemoglobin level, mean corpuscular volume and white blood cell counts were significantly increased in treated rats at 2-13 weeks of administration. The covalent binding of m-chloraniline m-CA, (the hydrolytic metabolite of chlorpropham) was observed in hemoglobin or splenic protein of treated rats, but only small amounts of free m-CA were present in blood or spleen. Congestion, hemosiderin deposits, extramedullary hemopoiesis and lymphoid atrophy in spleen and hyperplasia of hemopoietic cells in bone marrow were observed in treated rats at 2-13 weeks and fibrosis in splenic capsule were observed in treated rats at 4-13 weeks. The pathological changes in spleen rather than hematological changes progressed during administration, suggesting splenotoxicity of CIPC in rats.

Phenotypic changes associated with exogenous expression of p16INK4a in human glioma cells.

The tumor suppressor p16/CDKN2A/INK4a gene is frequently mutated, mostly by homozygous deletions in high-grade gliomas. Although the p16 protein suppresses cell proliferation primarily through inhibition of cell-cycle progression at the G1 phase, other phenotypic changes in glioma cells associated with p16INK4a alterations have not been fully described. To determine the roles of p16 alterations in glioma formation, we have established ecdysone-driven inducible p16 expression in the human glioblastoma cell line CL-4, which were derived from p16-null U87MG cells. Here we show that exogenous p16 expression in CL-4 cells results in morphological changes, with large and flattened cytoplasm, which are associated with increased formation of cytoplasmic actin-stress fibers and vinculin accumulation in the focal adhesion contacts. Adhesion of CL-4 cells to extracellular matrix proteins, such as laminin, fibronectin, and type IV collagen, significantly increased upon exogenous p16 expression, which correlated with increased expression of integrin alpha5 and alphav. Expression of a small GTP-binding protein, Rac, also decreased. Following epidermal growth factor stimulation, phosphorylation of MAP kinases ERK1 and 2 and induction of an early immediate gene product, c-Fos, were significantly reduced in CL-4 cells with p16 expression. These results suggest that the tumor suppressor p16 may exert its antitumor effects through modulation of multiple aspects of glioblastoma phenotypes, including proliferation, invasiveness, and responsiveness to extracellular growth stimuli.

Evaluating the performance of a hybrid artificial liver support system with a recoverable hepatic failure rat model.

To evaluate the performance of an artificial liver, we created a recoverable hepatic failure rat model. This involves a 30-60 minute warm ischemia, via clamping, of one-third of the liver with a partial (two-thirds) hepatectomy. Variations on this method provide for the possibility of several modes of hepatic failure. Survival time of the rats was prolonged (35%) by applying our hybrid artificial liver. However, the extracorporeal circulation is a considerable burden to the rat. Therefore, we need to apply the hybrid artificial liver intermittently and repeatedly.