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We report the critical behavior of steady quantum turbulence in superfluid 4 He. By using a thin vibrating wire with no bridge vortices in the superfluid, we find that lifetime of turbulent state for a given driving force reveals an exponential distribution. The mean lifetime estimated from the distribution decreases exponentially but greatly below a critical injection power. We estimate the vortex line density in the turbulent state and find that this critical behavior arises when the interdistance between vortex lines becomes as large as the turbulent region.Superfluid turbulence has attracted renewed experimental and theoretical interest as a result of recent investigations. 1 Turbulence in superfluid 4 He at very low temperatures consists only of a tangle of quantized vortex lines that defines superfluid flow. Hence, the energy flux in superfluid turbulence is described by the motions of the vortex lines. The energy of flows circulating vortex cores cascades from large vortex loops to smaller loops by reconnection ͑Richardson cascade͒; Kelvin waves with scales smaller than the vortex line spacing form along vortex lines and transfer energy from large wavelengths to smaller wavelengths ͑Kelvin wave cascade͒. 2-4 Consequently, the turbulence energy cascades from large scales to small scales, eventually dissipating at high wave numbers. This process can be observed in the decay of the density of vortex lines in superfluid helium 5,6 even at very low temperatures where the normal-fluid component is almost absent.Motions of vortex lines are also manifested in the continuous generation of turbulence by oscillating structures in superfluid 4 He. Experimental studies using oscillating spheres, 7 wires, 8,9 grids, 10 and tuning forks 11,12 indicate that superfluid turbulence can be generated at oscillating velocities above a critical velocity of about 50 mm/s. Vortex lines form bridges between a structure and its surrounding boundaries and they are shaken by the oscillation, developing into turbulence at velocities exceeding the critical velocity. 13,14 In a previous study, we found that a vibrating wire in the absence of bridge vortices also generates turbulence after vortex rings are applied from a vortex ring generator to the wire. 15 In a turbulent state, the vibrating wire continues to generate vortex lines even when further vortex rings are not applied. At sufficiently high driving forces, the generation seems to continue indefinitely. The wire velocity remains constant during the generation of vortex lines. However, the generation will stop suddenly when the driving force is reduced. After that, the vibrating wire cannot generate turbulence even at high velocities. This behavior is in marked contrast to the responses of other oscillating structures with bridge vortices, with respect to intermittent switching between turbulent flow and laminar flow or, more precisely, potential flow. 16,17 A vibrating wire with no bridge vortices determines the lifetime of the turbulent state in the turbulentto-laminar transitio...

Cancer peptide vaccines are a promising cancer immunotherapy that can induce cancer-specific cytotoxic T lymphocytes (CTLs) in tumors. However, recent clinical trials of cancer vaccines have revealed that the efficacy of the vaccines is limited. Targeting single antigens and vaccination with short peptides are partly the cause of the poor clinical outcomes. We synthesized a novel multi-epitope long peptide, TAS0314, which induced multiple epitope-specific CTLs in HLA knock-in mice. It also showed superior epitope-specific CTL induction and antitumor activity. We also established a combination treatment model of vaccination with PD-1/PD-L1 blockade in HLA-A*2402 knock-in mice, and it showed a synergistic antitumor effect with TAS0314. Thus, our data indicated that TAS0314 treatment, especially in combination with PD-1/PD-L1 blockade, is a promising therapeutic candidate for cancer immunotherapy.

Objective: The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Methods: Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2 − (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER−/PR−/HER2− (triple negative). We also categorized patients' breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. Results: The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky performance status, HER2 status and the disease-free interval (from initial treatment to first recurrence) were shown to be significant prognostic factors (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+: relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk 1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Conclusions: Our data indicate that breast cancer-specific Graded Prognostic Assessment-based prediction will be helpful in determining appropriate therapeutic strategies for patients with brain metastasis from breast cancer.

Background: The objective of this study was to evaluate the accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes (LN) in breast cancer, to compare the results of FNAC and pathological examination, and to distinguish patients with 1 to 2 metastatic LNs from those with ≥3 metastatic LNs in patients with FNAC-positive patients. Patients and Methods: This study included 198 breasts of 196 patients with breast cancer who underwent FNAC and surgery for the primary and axilla without neoadjuvant chemotherapy from January 2010 to August 2016. Axillary nodal status was assessed by ultrasound (US), and whether FNAC-positive had three or more suspicious LNs on US imaging was examined. Results: The results of FNAC were positive in 75 (38%), negative in 97 (49%), suspicious in 2 (1%), indeterminate in 5 (2.5%), and insufficient in 19 patients (9.5%). FNAC sensitivity, specificity, positive predictive value, and negative predictive value were 62.6%, 100%, 100%, and 62.0%, respectively. Whereas 53% (18/34) of patients with false-negative FNAC had one metastatic LN on final pathology, 61% (47/77) patients who were FNACpositive had three or more metastatic LNs. In the FNAC-positive patients, all patients had ≥3 metastatic LNs if they had ≥3 suspicious LNs on US imaging. Conclusion: Patients with positive cytology were more likely to have ≥3 positive LNs compared to false-negative cytology patients. Patients with ≥3 abnormal LNs on US and positive FNAC might require axillary dissection.

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We generated a series of monochain HLA class I knock-in (KI) mouse strains, in which a chimeric HLA class I molecule (α1/α2 domain of HLA-A*0201, HLA-A*0301, HLA-A*2402, or HLA-A*3101 and α3 domain of H-2D) was covalently linked with 15 aa to human β-microglobulin (βm) and introduced into the endogenous mouse βm locus. In homozygous KI mice, mouse βm gene disruption resulted in loss of the endogenous H-2 class I molecules and reduction in the peripheral CD8 T cell population that was partially restored by monochain HLA class I expression. A gene dosage-dependent expression of HLA, similar to that in human PBMCs, was detected in heterozygous and homozygous HLA KI mice. Upon vaccination with various virus epitopes, HLA-restricted, epitope-specific CTLs were induced in HLA KI mice, similar to the response in the commonly used HLA transgenic mice. Importantly, the CTL responses induced in heterozygous KI mice were similar to those in homozygous KI mice. These results suggest that coexpression of H-2 class I does not affect HLA-restricted CTL responses in HLA KI mice, which differs from the situation reported for monochain HLA Tg × β2m mice. Furthermore, we generated double KI mice harboring two different HLA (HLA-A*2402 and HLA-A*0301) KI alleles, which showed a CTL response against both HLA-A24 and HLA-A3 epitopes when immunized with a mixture of both peptides. These results indicated that this HLA class I KI mouse model provides powerful research tools not only for the study of HLA class I-restricted CTL responses, but also for preclinical vaccine evaluation.