Ultrafast Electron-Electron Scattering in Metallic Phase of 2H-NbSe_{2} Probed by High Harmonic Generation.

Electron-electron scattering on the order of a few to tens of femtoseconds plays a crucial role in the ultrafast electron dynamics of conventional metals. When mid-infrared light is used for driving and the period of light field is comparable to the scattering time in metals, unique light-driven states and nonlinear optical responses associated with the scattering process are expected to occur. Here, we use high-harmonics spectroscopy to investigate the effect of electron-electron scattering on the electron dynamics in thin film 2H-NbSe_{2} driven by a mid-infrared field. We observed odd-order high harmonics up to 9th order as well as a broadband emission from hot electrons in the energy range from 1.5 to 4.0 eV. The electron-electron scattering time in 2H-NbSe_{2} was estimated from the broadband emission to be almost the same as the period of the mid-infrared light field. A comparison between experimental results and a numerical calculation reveals that competition and cooperation between the driving and scattering enhances the nonperturbative behavior of high harmonics in metals, causing a highly nonequilibrium electronic state corresponding to several thousand Kelvin.

Optimal selection of learning data for highly accurate QSAR prediction of chemical biodegradability: a machine learning-based approach.

Prior to the manufacture of new chemicals, regulations mandate a thorough review of the chemicals under risk management. This review involves evaluating their effects on the environment and human health. To assess these effects, a review report that conforms to the OECD Test Guidelines must be submitted to the regulatory body. One of the essential components of the report is an assessment of the biodegradability of chemicals in the environment. In addition to conventional methods, quantitative structure-activity relationship (QSAR) models have been developed to predict the properties of chemicals based on their structural features. Although a greater number of chemicals in the learning set may enhance the prediction accuracy, it may also lead to a decrease in accuracy due to the mixing of different structural features and properties of the chemicals. To improve the prediction performance, it is recommended to use only the appropriate data for biodegradability prediction as a training set. In this study, we propose a novel approach for the optimal selection of training set that enables a highly accurate prediction of the biodegradability of chemicals by QSAR. Our findings indicate that the proposed method effectively reduces the root mean squared error and improves the prediction accuracy.

Assessment of Heating on Titanium Alloy Cerebral Aneurysm Clips during 7T MRI.

BACKGROUND AND PURPOSE: Patients with cerebral aneurysms often undergo MR imaging after microsurgical clipping. Ultra-high-field MR imaging at 7T may provide high diagnostic capability in such clinical situations. However, titanium alloy clips have safety issues such as adverse interactions with static magnetic fields and radiofrequency-induced heating during 7T MR imaging. The purpose of this study was to quantitatively assess temperature increases on various types of titanium alloy aneurysm clips during 7T MR imaging. MATERIALS AND METHODS: Five types of titanium alloy aneurysm clips were tested, including combinations of short, long, straight, angled, and fenestrated types. Each clip was set in a phantom filled with gelled saline mixed with polyacrylic acid and underwent 7T MR imaging with 3D T1WI with a spoiled gradient recalled acquisition in the steady-state technique. Temperature was chronologically measured at the tips of the clip blade and head, angled part of the clip, and 5 mm from the tip of the clip head using MR imaging-compatible fiber-optic thermometers. RESULTS: Temperature increases at all locations for right-angled and short straight clips were <1°C. Temperature increases at the angled part for the 45° angled clip and the tip of the clip head for the straight fenestrated clip were >1°C. Temperature increases at all locations for the long straight clip were >2°C. CONCLUSIONS: Temperature increases on the right-angled and short straight clips remained below the regulatory limit during 7T MR imaging, but temperature increases on the 45° angled, straight fenestrated, and long straight clips exceeded this limit.

Real-Space Observation of Emergent Complexity of Phase Evolution in Micrometer-Sized IrTe_{2} Crystals.

We report complex behaviors in the phase evolution of transition-metal dichalcogenide IrTe_{2} thin flakes, captured with real-space observations using scanning Raman microscopy. The phase transition progresses via growth of a small number of domains, which is unlikely in statistical models that assume a macroscopic number of nucleation events. Consequently, the degree of phase evolution in the thin flakes is quite variable for the selected specimen and for a repeated measurement sequence, representing the emergence of complexity in the phase evolution. In the ∼20-µm^{3}-volume specimen, the complex phase evolution results in the emergent coexistence of a superconducting phase that originally requires chemical doping to become thermodynamically stable. These findings indicate that the complexity involved in phase evolution considerably affects the physical properties of a small-sized specimen.

Effect of zymosan on feed passage in the digestive tract in chicks.

1. The purpose of the present study was to examine whether zymosan, which is a component of fungi, affects feed passage through the digestive tract in chicks (Gallus gallus).2. Intraperitoneal (IP) injection of 2.5 mg zymosan significantly reduced the crop-emptying rate and this effect was similar to that of 100 µg lipopolysaccharide (LPS). Zymosan affected phenol red transit from the proventriculus.3. Zymosan significantly affected the gene expression of interleukin-1ß (IL-1ß), IL-6, IL-8 and histidine decarboxylase in various regions of the digestive tract.4. The present study suggested that zymosan retarded feed passage through the digestive tract in chick and interleukins and histamine may be participating in this process.

Rechallenge of voriconazole successfully tolerated after hepatic toxicity.

Infections caused by Aspergillus species are often life-threatening. Drugs effective for Aspergillus infection are limited. Voriconazole is one of the most important drugs, however, considerable portion of patients experience liver toxicity and have to stop the drug administration. We frequently experience liver toxicity even though the serum concentration of voriconazole is within the target range. Historically, in some life-threatening situations like tuberculosis, where a suitable alternative is unavailable, rechallenge has been attempted. However, there have been no report on the rechallenge of voriconazole. We report cases of successful re-administration of voriconazole after liver toxicity.

Resonantly Driven Singlet-Triplet Spin Qubit in Silicon.

We report implementation of a resonantly driven singlet-triplet spin qubit in silicon. The qubit is defined by the two-electron antiparallel spin states and universal quantum control is provided through a resonant drive of the exchange interaction at the qubit frequency. The qubit exhibits long T_{2}^{*} exceeding 1 µs that is limited by dephasing due to the ^{29}Si nuclei rather than charge noise thanks to the symmetric operation and a large micromagnet Zeeman field gradient. The randomized benchmarking shows 99.6% single gate fidelity which is the highest reported for singlet-triplet qubits.

Quantum non-demolition readout of an electron spin in silicon.

While single-shot detection of silicon spin qubits is now a laboratory routine, the need for quantum error correction in a large-scale quantum computing device demands a quantum non-demolition (QND) implementation. Unlike conventional counterparts, the QND spin readout imposes minimal disturbance to the probed spin polarization and can therefore be repeated to extinguish measurement errors. Here, we show that an electron spin qubit in silicon can be measured in a highly non-demolition manner by probing another electron spin in a neighboring dot Ising-coupled to the qubit spin. The high non-demolition fidelity (99% on average) enables over 20 readout repetitions of a single spin state, yielding an overall average measurement fidelity of up to 95% within 1.2 ms. We further demonstrate that our repetitive QND readout protocol can realize heralded high-fidelity (>99.6%) ground-state preparation. Our QND-based measurement and preparation, mediated by a second qubit of the same kind, will allow for a wide class of quantum information protocols with electron spins in silicon without compromising the architectural homogeneity.

Effects of toll-like receptor-7 agonists on feeding behaviour, voluntary activity, cloacal temperature and crop emptying in chicks.

1. The purpose of the present study was to determine if an intraperitoneal injection of two toll-like receptor-7 (TLR7) agonists, imiquimod and resiquimod, affect feed intake, voluntary activity, cloacal temperature, crop-emptying rate, plasma corticosterone (CORT) and glucose concentrations, and splenic gene expression of cytokines in chicks (Gallus gallus). 2. Although intraperitoneal injection of 100 µg imiquimod significantly increased splenic gene expression of interleukin-1ß (IL-1ß), IL-6, IL-8, and interferon-γ (IFN-γ), it did not affect feed intake, voluntary activity, cloacal temperature, crop-emptying rate or plasma constituents. 3. Intraperitoneal injection of 100 µg resiquimod significantly decreased feed intake, voluntary activity, cloacal temperature, crop-emptying rate and increased plasma corticosterone concentrations. 4. Intraperitoneal injection of resiquimod significantly increased splenic gene expression of IL-1ß, IL-6, IL-8, IFN-γ, and tumour necrosis factor-like cytokine 1A. 5. The results showed that activation of TLR7 is associated with anorexia, hypoactivity, hypothermia, disturbance of feed passage in the digestive tract and the response to stress in chicks.

Physiological responses to central and peripheral injection of polyinosinic-polycytidylic acid in chicks.

1. The purpose of the present study was to determine if intracerebroventricular (ICV) and intraperitoneal (IP) injection of polyinosinic-polycytidylic acid (poly I:C), a viral mimetic that binds to toll-like receptor-3 (TLR3), affects food intake, voluntary activity, cloacal temperature, plasma corticosterone (CORT) and glucose concentrations, and crop emptying rate in chicks (Gallus gallus). 2. Both ICV and IP injection of poly I:C significantly decreased food intake. 3. IP but not ICV injection of poly I:C significantly suppressed voluntary activity, whereas ICV injection decreased time spent sitting. Both ICV and IP injection of poly I:C significantly increased plasma CORT and glucose concentration. Neither ICV nor IP injection of poly I:C significantly affected cloacal temperature. 4. In addition, ICV injection of poly I:C significantly reduced crop emptying rate, whereas IP injection had no effect. 5. These results suggested that central TLR3 is related to anorexia, stress response and retardation of crop emptying while peripheral TLR3 is related to anorexia, change in behaviour and stress responses during viral infection in chicks.

A fast quantum interface between different spin qubit encodings.

Single-spin qubits in semiconductor quantum dots hold promise for universal quantum computation with demonstrations of a high single-qubit gate fidelity above 99.9% and two-qubit gates in conjunction with a long coherence time. However, initialization and readout of a qubit is orders of magnitude slower than control, which is detrimental for implementing measurement-based protocols such as error-correcting codes. In contrast, a singlet-triplet qubit, encoded in a two-spin subspace, has the virtue of fast readout with high fidelity. Here, we present a hybrid system which benefits from the different advantages of these two distinct spin-qubit implementations. A quantum interface between the two codes is realized by electrically tunable inter-qubit exchange coupling. We demonstrate a controlled-phase gate that acts within 5.5 ns, much faster than the measured dephasing time of 211 ns. The presented hybrid architecture will be useful to settle remaining key problems with building scalable spin-based quantum computers.

The induced RNA-binding protein, HuR, targets 3'-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis.

RNA-binding proteins (RBPs) regulate mRNA stability by binding to the 3'-untranslated region (UTR) region of mRNA. Human antigen-R (HuR), one of the RBPs, is involved in the progression of diseases, such as rheumatoid arthritis, diabetes mellitus and some inflammatory diseases. Interleukin (IL)-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontal disease (PD) is also an inflammatory disease caused by elevations in IL-6 following an infection by periodontopathogenic bacteria. The involvement of HuR in the progression of PD was assessed using in-vitro and in-vivo experiments. Immunohistochemistry of inflamed periodontal tissue showed strong staining of HuR in the epithelium and connective tissue. HuR mRNA and protein level was increased following stimulation with Porphyromonas gingivalis (Pg), one of the periodontopathogenic bacteria, lipopolysacchride (LPS)-derived from Pg (PgLPS) and tumour necrosis factor (TNF)-α in OBA-9, an immortalized human gingival epithelial cell. The luciferase activity of 3'-UTR of IL-6 mRNA was increased by TNF-α, Pg and PgLPS in OBA-9. Luciferase activity was also increased in HuR-over-expressing OBA-9 following a bacterial stimulation. Down-regulation of HuR by siRNA resulted in a decrease in mRNA expression and production of IL-6. In contrast, the over-expression of HuR increased IL-6 mRNA expression and production in OBA-9. The HuR inhibitor, quercetin, suppressed Pg-induced HuR mRNA expression and IL-6 production in OBA-9. An oral inoculation with quercetin also inhibited bone resorption in ligature-induced periodontitis model mice as a result of down-regulation of IL-6. These results show that HuR modulates inflammatory responses by regulating IL-6.

Response to Lefebvre et al.

Congenital scoliosis (CS) is a common vertebral malformation with incidence of up to 1 of 1000 births worldwide. Recently, TBX6 has been reported as the first disease gene for CS: about 10% of CS patients are compound heterozygotes of rare null mutations and a common haplotype composed by 3 SNPs in TBX6. Lefebvre et al in this journal reported that 2 patients with spondylocostal dysostosis (SCD), a rare skeletal dysplasia affecting spine and ribs also have TBX6 mutations: 1 carried the microdeletion and a rare missense variant, and another 2 rare missense variants. We investigated the pathogenicity of the 3 missense variants in SCD by a luciferase assay. The results were negative for the proposal of Lefebvre et al. We consider these 2 SCD patients are more probably compound heterozygotes of null mutations and a common risk haplotype just as CS patients with TBX6 mutations.

MSC/ECM Cellular Complexes Induce Periodontal Tissue Regeneration.

Transplantation of mesenchymal stem cells (MSCs), which possess self-renewing properties and multipotency, into a periodontal defect is thought to be a useful option for periodontal tissue regeneration. However, developing more reliable and predictable implantation techniques is still needed. Recently, we generated clumps of an MSC/extracellular matrix (ECM) complex (C-MSC), which consisted of cells and self-produced ECM. C-MSCs can regulate their cellular functions in vitro and can be grafted into a defect site, without any artificial scaffold, to induce bone regeneration. Accordingly, this study aimed to evaluate the effect of C-MSC transplantation on periodontal tissue regeneration in beagle dogs. Seven beagle dogs were employed to generate a premolar class III furcation defect model. MSCs isolated from dog ilium were seeded at a density of 7.0 × 104 cells/well into 24-well plates and cultured in growth medium supplemented with 50 µg/mL ascorbic acid for 4 d. To obtain C-MSCs, confluent cells were scratched using a micropipette tip and were then torn off as a cellular sheet. The sheet was rolled up to make round clumps of cells. C-MSCs were maintained in growth medium or osteoinductive medium (OIM) for 5 or 10 d. The biological properties of C-MSCs were evaluated in vitro, and their periodontal tissue regenerative activity was tested by using a dog class III furcation defect model. Immunofluorescence analysis revealed that type I collagen fabricated the form of C-MSCs. OIM markedly elevated calcium deposition in C-MSCs at day 10, suggesting its osteogenic differentiation capacity. Both C-MSCs and C-MSCs cultured with OIM transplantation without an artificial scaffold into the dog furcation defect induced periodontal tissue regeneration successfully compared with no graft, whereas osteogenic-differentiated C-MSCs led to rapid alveolar bone regeneration. These findings suggested that the use of C-MSCs refined by self-produced ECM may represent a novel predictable periodontal tissue regenerative therapy.

A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer.

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).

Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m-2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. CONCLUSIONS: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

IκBNS induces Muc5ac expression in epithelial cells and causes airway hyper-responsiveness in murine asthma models.

BACKGROUND: In allergic asthma, environmental allergens including house dust mite (HDM) trigger pattern recognition receptors and activate downstream signaling pathways including NF-κB pathways not only in immune cells but also in airway epithelial cells. Recent studies have shown that NF-κB activation is regulated positively or negatively depending on the cellular context by IκBNS (encoded by the gene Nfkbid), one of atypical IκB proteins, in the nucleus. Therefore, we hypothesized that IκBNS expressed in immune cells or epithelial cells is involved in the regulation of asthmatic responses. AIM: To determine the roles of IκBNS in HDM-induced asthmatic responses. METHODS: Roles of IκBNS in HDM-induced airway inflammation and airway hyper-responsiveness (AHR) were examined by using IκBNS-deficient (Nfkbid-/- ) mice. Roles of IκBNS expressed in hematopoietic cells and nonhematopoietic cells were separately evaluated by bone marrow chimeric mice. Roles of IκBNS expressed in murine tracheal epithelial cells (mTECs) were examined by air-liquid interface culture. RESULTS: House dust mite-induced airway inflammation and AHR were exacerbated in mice lacking IκBNS in hematopoietic cells. In contrast, HDM-induced airway inflammation was exacerbated, but AHR was attenuated in mice lacking IκBNS in nonhematopoietic cells. The induction of Muc5ac, a representative mucin in asthmatic airways, was reduced in Nfkbid-/- mTEC, whereas the induction of Spdef, a master regulator of goblet cell metaplasia, was not impaired in Nfkbid-/- mTEC. Moreover, IκBNS bound to and activated the MUC5AC distal promoter in epithelial cells. CONCLUSION: IκBNS is involved in inducing Muc5ac expression in lung epithelial cells and causing AHR in HDM-induced asthma models.

Influence of ABCB1 and ABCG2 polymorphisms on the antiemetic efficacy in patients with cancer receiving cisplatin-based chemotherapy: a TRIPLE pharmacogenomics study.

Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.