Dynamics of the Vortex-Particle Complexes Bound to the Free Surface of Superfluid Helium.

We present an experimental and theoretical study of the 2D dynamics of electrically charged nanoparticles trapped under a free surface of superfluid helium in a static vertical electric field. We focus on the dynamics of particles driven by the interaction with quantized vortices terminating at the free surface. We identify two types of particle trajectories and the associated vortex structures: vertical linear vortices pinned at the bottom of the container and half-ring vortices traveling along the free surface of the liquid.

Ripplonic Lamb Shift for Electrons on Liquid Helium.

We study the shift of the energy levels of electrons on a helium surface due to the coupling to the quantum field of surface vibrations. As in quantum electrodynamics, the coupling is known, and it is known to lead to an ultraviolet divergence of the level shifts. We show that there are diverging terms of different nature and use the Bethe-type approach to show that they cancel each other, to leading order. This resolves the long-standing theoretical controversy and explains the existing experiments. The results allow us to study the temperature dependence of the level shift. The predictions are in good agreement with the experimental data, with no adjustable parameters.

Metallic nanowires and mesoscopic networks on a free surface of superfluid helium and charge-shuttling across the liquid-gas interface.

We investigate the motion of electrically charged metallic nano- and microparticles produced by laser ablation in He gas and injected into superfluid helium. In the presence of a vertical static electric field, the particles either perform a repetitive shuttle-like motion transporting the charge across the liquid-gas interface or become trapped under the free surface of liquid He and coalesce into long filaments and complex two-dimensional mesoscopic networks. A classical electrohydrodynamic model is used to describe the motion of charged microparticles in superfluid He. The resulting filaments and networks are analyzed using electron microscopy. It is demonstrated that each filament is in fact composed of a large number of nanowires with a characteristic diameter of order of 10 nm and extremely large aspect ratios.

Critical Behavior of Alternately Pumped Nuclear Spins in Quantum Dots.

Nuclear spins in a spin-blocked quantum dot can be pumped and eventually polarized in either of two opposite directions that are selected by applying two different source-drain voltages. Applying a square pulse train as the source-drain voltage can continuously switch the pumping direction alternately. We propose and demonstrate a critical behavior in the polarization after alternate pumping, where the final polarization is sensitive to the initial polarization and pulse conditions. This sensitivity leads to stochastic behavior in the final polarization under nominally the same pumping conditions.

Maximum flexion and lateral rollback revealed better patient satisfaction after total knee arthroplasty.

INTRODUCTION: Patient satisfaction is an important outcome of total knee arthroplasty (TKA). However, we cannot predict how and why patients are satisfied or dissatisfied with TKA. The hypothesis of this study was that patient-reported outcomes (PROs) correlate with in vivo kinematics after TKA. MATERIALS AND METHODS: One hundred knees were analyzed after TKA. The in vivo kinematics of deep knee bending motion were estimated from single-plane fluoroscopy using a two-to-three-dimensional registration technique. Active knee flexion, femoral rotation and rollback were evaluated. The PROs were obtained after surgery using the 2011 Knee Society Scoring System (KSS), and their relationship with in vivo kinematics was determined. RESULTS: The average minimum and maximum flexion were -2.4 ± 7.3° and 113.2 ± 13.6°, respectively. The average femoral rotation was 7.4 ± 3.4°, and the average medial and lateral rollback were 2.4 ± 4.8 mm and 7.2 ± 5.6 mm, respectively. The multiple regression analysis revealed that the maximum flexion angle significantly contributed to symptoms and satisfaction. In addition, lateral rollback was also a significant factor affecting patient satisfaction. Lateral rollback and lateral Anterior-Posterior (AP) position at maximum flexion were correlated with the maximum flexion angle, whereas femoral rotation did not correlate with flexion angles. CONCLUSIONS: Maximum flexion and lateral rollback are important for better patient satisfaction after TKA. To obtain the maximum flexion angle, it was necessary to perform the normal kinematic pattern with a large amount of lateral rollback.

Commensurability-dependent transport of a Wigner crystal in a nanoconstriction.

We present the first transport measurements of a classical Wigner crystal through a constriction formed by a split-gate electrode. The Wigner crystal is formed on the surface of superfluid helium confined in a microchannel. At low temperatures, the current is periodically suppressed with increasing split-gate voltage, resulting in peaklike transport features. We also present the results of molecular dynamics simulations that reproduce this phenomenon. We demonstrate that, at the split-gate voltages for which the current is suppressed, the electron lattice is arranged such that the stability of particle positions against thermal fluctuations is enhanced. In these configurations, the suppression of transport due to interelectron Coulomb forces becomes important.

Staircaselike suppression of supersolidity under rotation.

There are a number of distinct signatures of superfluids, one of which is the appearance of quantized vortices. There have been some attempts to understand the putative supersolid 4He in the vortex framework, but no conclusive evidence that supports the existence of the vortices has been reported. Here, we investigate the rotation velocity dependence of the torsional oscillation of solid 4He at various temperatures. The velocity sweep reveals intriguing periodic staircaselike features below about 300 mK. The staircase patterns show remarkable periodicity, and we interpret these patterns as a consequence of vortex injection. However, there are some features that cannot be accounted for with simple injection of vortices into superfluid, and further investigation is required.

A retrospective analysis of endometrial carcinoma cases surgically treated with or without para-aortic lymph node dissection followed by adjuvant chemotherapy.

PURPOSE: To analyze the efficacies of para-aortic node (PAN) dissection for patients undergoing surgery and adjuvant chemotherapy for endometrial carcinomas. METHODS: At the Osaka University Hospital and the Kaizuka City Hospital in Osaka, Japan, either pelvic lymph nodes (PLN) plus para-aortic lymph nodes (PAN) or PLN-only dissections were performed for endometrial carcinomas. An adjuvant chemotherapy using paclitaxel, epirubicin, and carboplatin was conducted for all such patients. A retrospective comparison of the efficacy of PAN dissection was conducted. RESULTS: Disease-free and overall survivals and frequency of PAN involvement at the first recurrence did not exhibit a statistically significant difference between the PLN-only group and the PLN + PAN group. Operation time was significantly longer in the PLN + PAN group than the PLN-only group, and the total blood loss was also significantly greater in the PLN+PAN group. CONCLUSION: PAN dissection may be omitted, without adverse effect on prognosis, for endometrial carcinoma patients with recurrence risks who undergo adjuvant chemotherapy using platinum, anthracycline and taxane derivatives.

Voltage-selective bidirectional polarization and coherent rotation of nuclear spins in quantum dots.

We propose and demonstrate that the nuclear spins of the host lattice in GaAs double quantum dots can be polarized in either of two opposite directions, parallel or antiparallel to an external magnetic field. The direction is selected by adjusting the dc voltage. This nuclear polarization manifests itself by repeated controlled electron-nuclear spin scattering in the Pauli spin-blockade state. Polarized nuclei are also controlled by means of nuclear magnetic resonance. This Letter confirms that the nuclear spins in quantum dots are long-lived quantum states with a coherence time of up to 1 ms, and may be a promising resource for quantum-information processing such as quantum memories for electron spin qubits.

Point-contact transport properties of strongly correlated electrons on liquid helium.

We present transport measurements of a nondegenerate two-dimensional electron system on the surface of liquid helium at a point constriction. The constriction is formed in a microchannel by a split gate beneath the helium surface. The electrostatic energy of the electron system, which depends in part on the electron density, determines the split-gate voltage threshold of current flow through the constriction. Steplike increases in conductance are observed as the confinement strength is reduced. As the Coulomb interaction between electrons is strong, we attribute this effect to the increase in the number of electrons that can pass simultaneously through the constriction. Close to the threshold, single-electron transport is observed.

Enteroviruses, type 1 diabetes and hygiene: a complex relationship.

Type 1 diabetes (T1D) is an autoimmune disease in which the immune system mounts an attack on the host's insulin-producing beta cells. Because most cases of T1D cannot be attributed only to individual genetics, it is strongly inferred that there is a significant environmental contribution, such as infection, impacting disease development. The human enteroviruses (HEV) are common picornaviruses often implicated as triggers of human T1D, although precisely which of the numerous HEV may be involved in human T1D development is unknown. Experiments using non-obese diabetic (NOD) mice, commonly used to model T1D, show that induction of T1D by HEV infection in NOD mice is a multifactorial process involving both the virus and the host. Interestingly, results demonstrate that HEV infection of NOD mice can also induce long-term protection from T1D under certain conditions, suggesting that a similar mechanism may occur in humans. Based upon both experimental animal and observational human studies, we postulate that HEV have a dual role in T1D development and can either cause or prevent autoimmune disease. Whichever outcome occurs depends upon multiple variables in the host-virus equation, many of which can be deduced from results obtained from NOD mouse studies. We propose that the background to the sharply rising T1D incidences observed in the 20th century correlates with increased levels of hygiene in human societies. Viewing T1D in this perspective suggests that potential preventative options could be developed.

An in vitro evaluation of two resin-based sealers on proliferation and differentiation of human periodontal ligament cells.

AIM: To evaluate the effects of a polymethyl methacrylate resin-based sealer [Superbond sealer (SB)] on the proliferation and osteogenic differentiation of human periodontal ligament cells (HPDLCs) in vitro, compared with a methacrylate resin-based sealer [Epiphany SE sealer (EP)]. METHODOLOGY: Human periodontal ligament cells were obtained from of healthy third molar teeth of two participants with informed consent. To determine the effects of the eluent from set resin sealers on HPDLCs, the 7-day-washed (washed) or non-washed freshly prepared (fresh) set SB or EP discs were prepared. Cells cultured on these discs were evaluated by the WST-1 proliferation assay and scanning electron microscopy (SEM). The osteogenic differentiation of HPDLCs on washed SB discs was then evaluated by gene expression analysis of osteopontin (OPN) and osteocalcin (OCN) by using quantitative RT-PCR. RESULTS: Human periodontal ligament cells exhibited growth on washed SB discs, whereas fresh SB and EP discs and washed EP discs inhibited proliferation of HPDLCs. SEM observation revealed that HPDLCs tightly attached and spread on the surface of washed SB discs, whilst no HPDLCs were observed on the surface of fresh and washed EP discs. Furthermore, HPDLCs significantly upregulated gene expressions of OPN and OCN when cultured on washed SB discs in osteogenic differentiation medium for 2 weeks. CONCLUSIONS: Although Superbond sealer initially exerted cytotoxic effects on HPDLCs, these effects were reduced during washing for 7 days compared to EP, which continued to be cytotoxic even though the specimens were washed for the same period of time. Washed Superbond allowed HPDLCs to differentiate into osteogenic cells.

Surgical results of Hybrid Mita method to idiopathic scoliosis: minimum two years follow-up.

Hybrid Mita (Suzuki) method is a newly developed technique of scoliosis surgery. This concept consists of three components: rib mobilization, rod rotation maneuver and hook rotation maneuver, which does not require intra-operative CT scan with lower risk of screw malposition. The aim of this study is to evaluate the efficacies of this method for correction in scoliosis. : This is a retrospective observational study, consist of eighty-nine idiopathic scoliosis patients who underwent this method between 2009 and 2016 with minimum 2-years follow-up. The curve pattern, Cobb angle, hump height and angle, peri-operative events and complications were analyzed. The mean pre- and post-operative Cobb angle was 50.9° and 10.1°, respectively. The average correction rate was 80.5%. Hump height was reduced from 20.2 mm to 9.8 mm and hump angle reduced from 13.1° to 6.1° in average. The correction loss at the final follow-up was 0.3° in average. There were two local superficial infection cases, but there was no instrumentation failure such as malposition or dislodgement, or pseudarthrosis. This novel method is promising to provide excellent clinical correction to idiopathic scoliosis, which is no less than all pedicle screw constructs. The technique of the skillful utilization of hooks in spinal surgery should not perish from the stage.

Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer.

Surgery alone or combined with chemo- and/or radiation therapy remains the primary treatment for gastric cancer (GC) to date and immunotherapeutic tools such as monoclonal antibodies are only slowly being implemented. This is partly due to the fact that the immune microenvironment in GC during chemoradiation and other treatment modalities is still poorly understood. 7 gastric cancer (GC) cell lines were tested for their response to chemoradiation using 5-FU in combination with X-ray irradiation. We conducted flow cytometric analysis to determine the cells' ability to undergo immunogenic cell death (ICD) and their expression of the two immunosuppressive proteins programmed death-ligand 1 (PD-L1) and galectin-9 (Gal-9). We evaluated the overall immunogenicity of two cell lines (MKN7, MKN74) in co-culture experiments with human monocyte-derived dendritic cells (Mo-DCs). Chemoradiation induces distinct responses in different GC cell lines. We observe ICD in vitro in all tested GC cell lines in the form of calreticulin (CRT) translocation to the plasma membrane. As a resistance mechanism, these cells also upregulated Gal-9 and PD-L1. Mo-DC maturation experiments showed that GCs provoked the maturation of Mo-DCs after chemoradiation in vitro. The addition of α-PD-L1 blocking antibody further enhanced the immunogenicity of these cells while improving DC viability. Blocking Tim-3, as the main receptor for Gal-9, had no such effect. Our findings suggest that the benefits of chemoradiation can substantially depend on tumor subtype and these benefits can be offset by induced immune evasion in GC. Combination treatment using checkpoint inhibitors could potentially lead to enhanced immune responses and yield better patient outcomes.

Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma.

BACKGROUND: We previously reported that Trastuzumab- and Cetuximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) in cancer patients was impaired in comparison with that in healthy donors because of NK-cell dysfunction. In this study, we evaluated whether IL-21 could improve the impairment of ADCC in patients with oesophageal squamous cell carcinoma (ESCC), as IL-21 was reported to have the ability to activate NK cells. METHODS: We examined Trastuzumab- and Cetuximab-mediated ADCC of peripheral blood mononuclear cells (PBMCs) or of enriched NK cells derived from ESCC patients (n=20) and healthy donors (n=16) in the presence of IL-21. We further analysed ADCC-related molecules (perforin, granzyme-B, and CD247) on NK cells in response to IL-21. RESULTS: Trastuzumab- and Cetuximab-mediated ADCC of PBMCs or of enriched NK cells was enhanced by the addition of IL-21 in a dose-dependent manner and the levels of ADCC enhanced by IL-21 in patients were high enough in comparison with those in healthy donors, paralleling the upregulation of CD247 on NK cells. CONCLUSION: IL-21 could efficiently restore impaired ADCC in ESCC patients with the upregulation of CD247 molecules.

Inverse correlation of HER2 with MHC class I expression on oesophageal squamous cell carcinoma.

BACKGROUND: As HER2 is expressed in 30% of oesophageal squamous cell carcinomas (ESCCs), T-cell-based immunotherapy and monoclonal antibodies targeted against HER2 are attractive, novel approaches for ESCCs. However, it was shown that there is an inverse correlation between HER2 and MHC class I expression on tumours. Thus, the correlation between HER2 and MHC class I expressions on ESCC was evaluated. METHODS: Expressions of MHC class I and HER2 in ESCC tissues (n=80) and cell lines were assessed by immunohistochemistry, fluorescence in situ hybridisation (FISH), and flow cytometry. We investigated whether HER2 downregulation with small interfering RNA (siRNA) in ESCC cell lines could upregulate the expression of MHC class I and the antigen presentation machinery components, and could increase their sensitivity for tumour antigen-specific CTLs. RESULTS: There was an inverse correlation between HER2 and MHC class I expressions in both tumour tissues and cell lines. Downregulation of HER2 with siRNA resulted in the upregulation of MHC class I expression, leading to increased CTL recognition by tumour antigen-specific CTLs. CONCLUSION: HER2-overexpressing ESCC tumour cells showed a reduced sensitivity for CTLs through the downregulation of MHC class I.

Spin bottleneck in resonant tunneling through double quantum dots with different Zeeman splittings.

We investigated the electron transport property of the InGaAs/GaAs double quantum dots, the electron g factors of which are different from each other. We found that in a magnetic field, the resonant tunneling is suppressed even if one of the Zeeman sublevels is aligned. This is because the other misaligned Zeeman sublevels limit the total current. A finite broadening of the misaligned sublevel partially relieves this bottleneck effect, and the maximum current is reached when interdot detuning is half the Zeeman energy difference.

NK cell dysfunction with down-regulated CD16 and up-regulated CD56 molecules in patients with esophageal squamous cell carcinoma.

NK cells can be divided into two subsets, CD56(dim) and CD56(bright) NK cells, based on their expression of CD56 and CD16. In the present study, we analyzed NK cell dysfunction in patients with esophageal squamous cell carcinoma (ESCC), with a particular focus on the expression of CD16 and CD56 molecules. Expression of CD16 and CD56, and the distribution of CD56(dim) or CD56(bright) NK cells gated on CD56(+)CD3(-) NK cells were compared between ESCC patients (n= 40) and healthy donors (n= 38). Purified NK cells were evaluated for Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against epidermal growth factor receptor (EGFR)-expressing ESCC cell lines. Although there were no significant differences in the distribution of CD56(dim) and CD56(bright) NK cells between ESCC patients and healthy donors, down-regulated CD16 and up-regulated CD56 were significantly observed on NK cells of ESCC patients, paralleling the impairment of Cetuximab-mediated ADCC, in comparison with healthy donors. After patients received curative resections of ESCC, the down-regulated CD16 and up-regulated CD56 were significantly restored to the levels of healthy donors. Moreover, TGF-beta1 partially contributed to down-regulation of CD16 on NK cells. Down-regulated CD16 and up-regulated CD56 molecules on NK cells were observed in ESCC patients, resulting in NK cell dysfunction.

CCL17 and CCL22 chemokines within tumor microenvironment are related to infiltration of regulatory T cells in esophageal squamous cell carcinoma.

It has been reported that an increased population of regulatory T cells (T-regs) is one of the reasons for impaired anti-tumor immunity. We investigated the frequency of Foxp3(+) T-regs in tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) of patients with esophageal squamous cell carcinoma (ESCC). Furthermore, in order to elucidate the mechanisms behind T-regs accumulation within tumors, we evaluated the relationship between CCL17 or CCL22 expression and the frequency of Foxp3(+) T-regs. CD4(+)CD25(+)Foxp3(+) T-regs as a percentage of CD4(+) cells were counted by flow cytometry. The frequency of CCL17(+) or CCL22(+) cells among CD14(+) cells in tumors was also evaluated by flow cytometry. Moreover, an in vitro migration assay using T-regs derived from ESCC was performed in the presence of CCL17 or CCL22. The frequency of Foxp3(+) T-regs in TILs was significantly higher than that in the normal esophageal mucosa (24.6 +/- 10.0 vs 7.1 +/- 5.9%, P < 0.01). The frequency of Foxp3(+) T-regs in PBLs of ESCC patients was significantly higher than that in normal healthy donors (7.0 +/- 4.2 vs 2.5 +/- 1.0%, P < 0.01). Furthermore, the frequency of CCL17(+) or CCL22(+) cells among CD14(+) cells within tumors was significantly higher than that of normal esophageal mucosa, and there was a significant correlation between the frequency of CCL17(+) or CCL22(+) cells and Foxp3(+) T-regs in TILs. In addition, the in vitro migration assay indicated that T-regs were significantly induced to migrate by CCL17 or CCL22. In conclusion, CCL17 and CCL22 within the tumor are related to the increased population of Foxp3(+) T-regs in ESCC.

Downregulation of HLA Class I molecules in the tumour is associated with a poor prognosis in patients with oesophageal squamous cell carcinoma.

As antigenic peptides in the context of human leukocyte antigen (HLA) class I molecules are recognised by cytotoxic T lymphocytes (CTL), the downregulation of HLA class I molecules is one of the reasons why tumour cells can evade CTL-mediated anti-tumour immunity. In this study, we investigated HLA class I expression in oesophageal squamous cell carcinoma (ESCC) (n=70) and in their metastatic lesions (lymph nodes (n=40) and liver (n=3)), by immunohistochemistry with anti-HLA class I monoclonal antibody (EMR8-5). As a result, the downregulation of HLA class I expression in primary lesions of ESCC was observed in 43%, and that in metastatic lymph nodes was noted in 90%. Furthermore, patients with preserved HLA class I expression in primary tumours showed a better survival in comparison to those with downregulated HLA class I molecules (P<0.01). Furthermore, multivariate analysis using Cox's proportional hazards model revealed that the downregulated expression of HLA class I in primary lesions was an independent, unfavourable prognostic factor (P<0.01). In conclusion, the downregulation of HLA class I expression frequently occurred in primary tumour and, to a greater extent, in metastatic lesions of patients with ESCC and was associated with patient survival.