Large Diamagnetism and Electromagnetic Duality in Two-Dimensional Dirac Electron System.

A Dirac electron system in solids mimics relativistic quantum physics that is compatible with Maxwell's equations, with which we anticipate unified electromagnetic responses. We find a large orbital diamagnetism only along the interplane direction and a nearly temperature-independent electrical conductivity of the order of e^{2}/h per plane for the new 2D Dirac organic conductor, α-(BETS)_{2}I_{3}, where BETS is bis(ethylenedithio)tetraselenafulvalene. Unlike conventional electrons in solids whose nonrelativistic effects bifurcate electric and magnetic responses, the observed orbital diamagnetism scales with the electrical conductivity in a wide temperature range. This demonstrates that an electromagnetic duality that is valid only within the relativistic framework is revived in solids.

Regorafenib and reactive metabolite of sunitinib activate inflammasomes: Implications for multi tyrosine kinase inhibitor-Iiduced immune related adverse events.

Multi-targeted tyrosine kinase inhibitors have been developed for the treatment of various cancers, but they are associated with a significant incidence of idiosyncratic drug reactions (IDRs). There is compelling evidence that most IDRs are immune mediated. Activation of inflammasomes is often one of the early steps in the initiation of an immune response. This activation could involve the pharmacological effect of the drug, or it could involve the release of damage associated molecular patters (DAMPs) caused by a reactive metabolite. We tested whether sunitinib, regorafenib, lenvatinib and cabozantinib can directly activate inflammasomes in differentiated THP-1 cells. We found that regorafenib activated the inflammasome of differentiated THP-1 cells directly. We also found that the supernatant from the incubation of sunitinib with FLC-4 cells, which have a high capacity to metabolize drugs, led to activate the inflammasome of differentiated THP-1 cells. In the supernatant of FLC-4 cells with sunitinib, the heat shock protein (HSP) 90 was significantly increased. Sunitinib is known to be oxidized to generate a reactive, potentially toxic quinone imine. These results support the hypothesis that the reactive metabolite of sunitinib can cause the release of DAMPs from hepatocytes, which leads to activation of inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by regorafenib and sunitinib, which in some patients, can cause IDRs.

Quantum spin liquids unveil the genuine Mott state.

The localization of charge carriers by electronic repulsion was suggested by Mott in the 1930s to explain the insulating state observed in supposedly metallic NiO. The Mott metal-insulator transition has been subject of intense investigations ever since1-3-not least for its relation to high-temperature superconductivity4. A detailed comparison to real materials, however, is lacking because the pristine Mott state is commonly obscured by antiferromagnetism and a complicated band structure. Here we study organic quantum spin liquids, prototype realizations of the single-band Hubbard model in the absence of magnetic order. Mapping the Hubbard bands by optical spectroscopy provides an absolute measure of the interaction strength and bandwidth-the crucial parameters that enter calculations. In this way, we advance beyond conventional temperature-pressure plots and quantitatively compose a generic phase diagram for all genuine Mott insulators based on the absolute strength of the electronic correlations. We also identify metallic quantum fluctuations as a precursor of the Mott insulator-metal transition, previously predicted but never observed. Our results suggest that all relevant phenomena in the phase diagram scale with the Coulomb repulsion U, which provides a direct link to unconventional superconductivity in cuprates and other strongly correlated materials.

Correction to: Lower grip strength and dynamic body balance in women with distal radial fractures.

The article Lower grip strength and dynamic body balance in women with distal radial fractures, written by. K. Fujita, H. Kaburagi, A. Nimura, T. Miyamoto, Y. Wakabayashi, Y. Seki, H. Aoyama, H. Shimura, R. Kato, A. Okawa was originally published electronically on the publisher's internet portal.

Lower grip strength and dynamic body balance in women with distal radial fractures.

In this case-control study, we concluded that women with distal radial fractures who were surgically treated showed lower grip strength and dynamic body balancing than those of controls. These results suggest that measurements of grip strength and dynamic body balance may be useful screening tools to assess future fracture risk. INTRODUCTION: Patients with distal radial fractures (DRFs) are at risk of future fragility fractures. However, their physical characteristics and tendencies for falls remain unclear. We aimed to compare the physical characteristics of women with and without distal radial fractures. METHODS: We included 128 women with a DRF as their first fragility fracture (fracture group) who underwent surgical treatment. Concurrently, 128 age- and sex-matched participants without a history of fragility fractures were selected as controls (control group). The participants underwent assessments of grip strength and the body balancing ability test. Measurements were taken twice in the fracture group, at 2 weeks and 6 months postoperatively, and once in the control group. The body balancing ability test included the Functional Reach Test, Timed Up and Go test (TUG), 2-Step test (2ST), and Timed Uni-pedal Stance test. The participants also completed questionnaires about their health. RESULTS: There were no significant differences (p > 0.05) in patient characteristics between the groups. The fracture group showed lower grip strength across all age groups. In the DRF group, prolonged TUG time was observed at 2 weeks postoperatively in all age groups and at 6 months in participants aged 55-74 years; the 2ST score was significantly lower in participants aged between 65 and 74 years. CONCLUSIONS: Women with DRF demonstrated lower grip strength and dynamic body balancing ability. Lower grip strength and dynamic body balancing ability were identified as significant risk factors in women with DRF, suggesting that these may be useful screening tools to assess fracture risk.

Fragmented Electronic Spins with Quantum Fluctuations in Organic Mott Insulators Near a Quantum Spin Liquid.

Magnetic structures of organic Mott insulators X[Pd(dmit)_{2}]_{2} (X=Me_{4}P, Me_{4}Sb), of which electronic states are located near a quantum spin liquid (X=EtMe_{3}Sb), are demonstrated by ^{13}C nuclear magnetic resonance. Antiferromagnetic spectra and nuclear relaxations show two distinct magnetic moments within each Pd(dmit)_{2} molecule, which cannot be described by single band dimer-Mott model and requires intramolecular electronic correlation. This unconventional fragmentation of S=1/2 electron spin with strong quantum fluctuation is presumably caused by nearly degenerated intramolecular multiple orbitals, and shares a notion of quantum liquids where electronic excitations are fractionalized and S=1/2 spin is no longer an elementary particle.

Absence of Magnetic Thermal Conductivity in the Quantum Spin Liquid Candidate EtMe_{3}Sb[Pd(dmit)_{2}]_{2}.

We present the ultralow-temperature specific heat and thermal conductivity measurements on single crystals of triangular-lattice compound EtMe_{3}Sb[Pd(dmit)_{2}]_{2}, which has long been considered as a gapless quantum spin liquid candidate. In specific heat measurements, a finite linear term is observed, consistent with the previous work [S. Yamashita et al., Nat. Commun. 2, 275 (2011)NCAOBW2041-172310.1038/ncomms1274]. However, we do not observe a finite residual linear term in the thermal conductivity measurements, and the thermal conductivity does not change in a magnetic field of 6 T. These results are in sharp contrast to previous thermal conductivity measurements on EtMe_{3}Sb[Pd(dmit)_{2}]_{2} [M. Yamashita et al., Science 328, 1246 (2010)SCIEAS0036-807510.1126/science.1188200], in which a huge residual linear term was observed and attributed to highly mobile gapless excitations, likely the spinons of a quantum spin liquid. In this context, the true ground state of EtMe_{3}Sb[Pd(dmit)_{2}]_{2} has to be reconsidered.

Mott transition by an impulsive dielectric breakdown.

The transition of a Mott insulator to metal, the Mott transition, can occur via carrier doping by elemental substitution, and by photoirradiation, as observed in transition-metal compounds and in organic materials. Here, we show that the application of a strong electric field can induce a Mott transition by a new pathway, namely through impulsive dielectric breakdown. Irradiation of a terahertz electric-field pulse on an ET-based compound, κ-(ET) 2Cu[N(CN) 2]Br (ET:bis(ethylenedithio)tetrathiafulvalene), collapses the original Mott gap of ∼30 meV with a ∼0.1 ps time constant after doublon-holon pair productions by quantum tunnelling processes, as indicated by the nonlinear increase of Drude-like low-energy spectral weights. Additionally, we demonstrate metallization using this method is faster than that by a femtosecond laser-pulse irradiation and that the transition dynamics are more electronic and coherent. Thus, strong terahertz-pulse irradiation is an effective approach to achieve a purely electronic Mott transition, enhancing the understanding of its quantum nature.

Low-Energy Excitations in Quantum Spin Liquids Identified by Optical Spectroscopy.

The electrodynamic response of organic spin liquids with highly frustrated triangular lattices has been measured in a wide energy range. While the overall optical spectra of these Mott insulators are governed by transitions between the Hubbard bands, distinct in-gap excitations can be identified at low temperatures and frequencies, which we attribute to the quantum-spin-liquid state. For the strongly correlated ß^{'}-EtMe_{3}Sb[Pd(dmit)_{2}]_{2}, we discover enhanced conductivity below 175 cm^{-1}, comparable to the energy of the magnetic coupling J≈250 K. For ω→0, these low-frequency excitations vanish faster than the charge-carrier response subject to Mott-Hubbard correlations, resulting in a dome-shaped band peaked at 100 cm^{-1}. Possible relations to spinons, magnons, and disorder are discussed.

Changes in apolipoprotein B and oxidized low-density lipoprotein levels in gingival crevicular fluids as a result of periodontal tissue conditions.

BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic inflammatory disease caused by bacterial infection that can lead to tooth loss. Gingival crevicular fluid can be collected easily and noninvasively. We previously discovered the presence of apolipoprotein B (apoB), the main constituent of low-density lipoprotein, and oxidized low-density lipoprotein (oxLDL) in the gingival crevicular fluid of healthy subjects. In this study, we investigated whether periodontal conditions affect the levels of apoB and oxLDL in gingival crevicular fluid. MATERIAL AND METHODS: The study population comprised 11 patients with chronic periodontitis. A pair of gingival crevicular fluid samples was collected from each patient at a healthy site and at a site with periodontitis (baseline samples). Thereafter, gingival crevicular fluid samples were collected from the same patients again at 4 and 8 wk after scaling and root planing (SRP). The levels of apoB, oxLDL, protein and cytokines in gingival crevicular fluid, in addition to gingival crevicular fluid volume, were measured. RESULTS: At baseline, the levels of apoB and oxLDL in gingival crevicular fluid were higher at the sites with periodontitis than at the healthy sites. The levels of apoB and oxLDL at periodontal sites decreased after SRP. The level of oxLDL in gingival crevicular fluid correlated well with the probing pocket depth. The oxLDL : apoB ratio in gingival crevicular fluid was significantly higher than that in plasma. CONCLUSIONS: The levels of apoB and oxLDL in gingival crevicular fluid change according to the periodontal tissue conditions.

Identification and functional activity of a staphylocoagulase type XI variant originating from staphylococcal food poisoning isolates.

UNLABELLED: Staphylocoagulase, an extracellular protein secreted by Staphylococcus aureus, has been used as an epidemiological marker. At least 12 serotypes and 24 genotypes subdivided on the basis of nucleotide sequence have been reported to date. In this study, we identified a novel staphylocoagulase nucleotide sequence, coa310, from staphylococcal food poisoning isolates that had the ability to coagulate plasma, but could not be typed using the conventional method. The protein encoded by coa310 contained the six fundamental conserved domains of staphylocoagulase. The full-length nucleotide sequence of coa310 shared the highest similarity (77·5%) with that of staphylocoagulase-type (SCT) XIa. The sequence of the D1 region, which would be responsible for the determination of SCT, shared the highest similarity (91·8%) with that of SCT XIa. These results suggest that coa310 is a novel variant of SCT XI. Moreover, we demonstrated that coa310 encodes a functioning coagulase, by confirming the coagulating activity of the recombinant protein expressed from coa310. This is the first study to directly demonstrate that Coa310, a putative SCT XI, has coagulating activity. These findings may be useful for the improvement of the staphylocoagulase-typing method, including serotyping and genotyping. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to identify a novel variant of staphylocoagulase type XI based on its nucleotide sequence and to demonstrate coagulating activity in the variant using a recombinant protein. Elucidation of the variety of staphylocoagulases will provide suggestions for further improvement of the staphylocoagulase-typing method and contribute to our understanding of the epidemiologic characterization of Staphylococcus aureus.

The problems of cervical conization for postmenopausal patients.

PURPOSE: Cervical conization is the definitive treatment for women of any age who have cervical intraepithelial neoplasia (CIN). However, complications of the procedure have not been fully investigated in postmenopausal patients. The aim of this retrospective study was to evaluate the results and complications of cervical conization performed on premenopausal and postmenopausal patients. MATERIALS AND METHODS: This study recruited 405 patients who had undergone cervical laser conization. The median age was 36 years (range 20 to 75), and there were 361 (89.1%) premenopausal and 44 (10.9%) postmenopausal women. RESULTS: The length of the cone removed from the postmenopausal patients was significantly longer than the length from the premenopausal patients (17.9 ± 3.9 mm vs. 15.7 ± 3.6 mm, respectively; p = 0.02). The rate of positive endocervical cone margins from the premenopausal patients was significantly higher than the rate from the postmenopausal patients (9.1% vs. 0%, respectively; p = 0.037). The rate of cervical stenosis was significantly higher in postmenopausal patients than in premenopausal patients (59.1% vs. 8.3%; respectively; p < 0.0001). There was no difference in the rates of frequency of intraoperative complications. CONCLUSIONS: Although deep incision is mandatory for complete excision of CIN in postmenopausal patients, it increases the incidence of cervical stenosis. Cervical conization may be a less invasive surgical procedure for older women with CIN than hysterectomy; however, the risk of postoperative complications remains, causing a dilemma for physicians treating postmenopausal women with CIN.

Biweekly administration of docetaxel and carboplatin for advanced or recurrent endometrial and ovarian carcinomas.

OBJECTIVE: To examine efficacy and safety of biweekly administration of docetaxel and carboplatin for advanced or recurrent en- dometrial and ovarian carcinomas. MATERIAL AND METHODS: The recommended doses were determined in the phase I study. In the phase II feasibility study, the primary end-point was safety, and the secondary end-point was response rate and progression-free survival (PFS). RESULTS: The recommended doses of docetaxel and carboplatin were determined to be 45 mg/n(2) and AUC 3.0, respectively, in phase I study. In phase II feasibility study, no treatment-related death was observed. Most non-hematotoxicity cases were mild or moderate. Grade 4 neutropenia was confirmed in 13 patients (31.0%), whereas all cases showed tolerability with 2.6 days delay of anticancer drugs administration in both groups. Response rate was 55.0% in the ovarian carcinoma group, and average PFS was 8.7 months. In the endometrial carcinoma group, response rate was 50.0% and average PFS was 32.0 months. CONCLUSION: The present results showed that biweekly administration of docetaxel and carboplatin for advanced and recurrent endometrial and ovarian carcinomas results in acceptable side effects, response rate, and PFS.

Effect of hypoxia on UDP-glucuronosyl transferase mRNA expression in human hepatocarcinoma functional liver celL4 cell line.

Although hypoxic conditions have been reported to affect the expression levels of various enzymes like cytochrome P450, the effect of hypoxia for UDP-glucuronosyl transferase (UGT) expression has been unclear. We evaluated the mRNA expression of UGTs (UGT1A1·1A6·1A9·2B7) in a functional liver cell-4 (FLC-4) cell line by three-dimensional culture under hypoxic conditions (37 °C, 1% O2, 5% CO2) fo 7 days. The mRNA expression of UGT1A1·1A6·1A9·2B7 decreased significantly after 3 days and that of UGT1A1·1A6·1A9 decreased significantly after 7 days. Hypoxic conditions affect the expression levels of UGT enzymes, thus the adjustment of dosage and interval should be considered in drug therapy that metabolized by UGT.

Universality class of the mott transition.

Pressure dependence of the conductivity and thermoelectric power is measured through the Mott transition in the layer organic conductor EtMe_{3}P[Pd(dmit)_{2}]_{2}. The critical behavior of the thermoelectric effect provides a clear and objective determination of the Mott-Hubbard transition during the isothermal pressure sweep. Above the critical end point, the metal-insulator crossing, determined by the thermoelectric effect minimum value, is not found to coincide with the maximum of the derivative of the conductivity as a function of pressure. We show that the critical exponents of the Mott-Hubbard transition fall within the Ising universality class regardless of the dimensionality of the system.

Successful treatment of cerebral large vessel vasculitis in systemic lupus erythematosus with intravenous pulse cyclophosphamide.

A 39-year-old woman with a six-year history of systemic lupus erythematosus (SLE) was admitted because of a prolonged high fever, discoid rash, and multiple lymphadenopathies. She also developed pericarditis, and was treated with intravenous methylprednisolone pulse therapy followed by prednisolone 50 mg daily and cyclosporine 100 mg daily. Meanwhile, she had a progressive headache, and a brain MRI revealed right pons infarction, although she did not have any abnormal neurological findings. An MRA revealed obvious irregular narrowing in the basilar, right vertebral and right posterior cerebral artery. There was no evidence of antiphospholipid syndrome. We concluded that the cause of the asymptomatic brain infarction was cerebral large vessel vasculitis associated with neuropsychiatric SLE. Intravenous cyclophosphamide pulse therapy was started, and two months later, we confirmed that the irregular arterial narrowing had markedly ameliorated.Cerebral large vessel vasculitis in neuropsychiatric SLE is very rare, and a marked amelioration has not been reported to date. Here, we present a rare case of cerebral large vessel vasculitis treated successfully with a clear visual presentation.

Identification and characterization of novel Staphylococcus aureus pathogenicity islands encoding staphylococcal enterotoxins originating from staphylococcal food poisoning isolates.

AIMS: Horizontal transfer of Staphylococcus aureus pathogenicity islands (SaPIs) plays an important role in acquiring pathogenicity. This study aimed to identify novel SaPIs encoding staphylococcal enterotoxins (SEs) and to characterize their SE productivity and replication process. METHODS AND RESULTS: Four novel SaPIs (SaPITokyo12413, SaPITokyo11212, SaPITokyo12571 and SaPITokyo12381) were determined using the SaPI scanning method. These SaPIs were composed of mosaic structures containing reported sequences. Four strains harbouring novel SaPIs produced significant amounts of SEs to cause staphylococcal food poisoning (SFP). With focus on the interaction between the replication initiator protein (Rep) and the replication origin (ori sites) that are proposed to be important for the replication of SaPIs, each Rep was prepared and their two functions were confirmed: binding activity to ori sites and helicase activity. These activities were present in the Reps of SaPITokyo11212, SaPITokyo12571 and SaPITokyo12381, but were both absent in the Rep of SaPITokyo12413. CONCLUSIONS: All four novel SaPIs could give sufficient toxicity to Staph. aureus to cause SFP. However, SaPITokyo12413 may be restricted in its replication capacity, suggesting that it lacks transfer ability unlike the other SaPIs. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report to identify four novel SE-encoding SaPIs and to examine their toxicity and replication capacity. Because SaPIs deeply participate in SE acquisition, it is important to elucidate their characteristics for understanding Staph. aureus virulence and speculating regarding its evolution as a pathogen.

Risk factors of recurrent sickness absence due to depression: a two-year cohort study among Japanese employees.

PURPOSE: Depression has a high recurrence rate among employees. There have been few studies investigating risk factors for recurrent sickness absence due to depression after return to work (RTW). The objective of this study was to identify potential risk factors. METHODS: Subjects were 540 full-time employees at the biggest telecommunication company in Japan who returned to work from April 2002 to March 2008 after their first leave of absence due to depression. The Cox proportional hazard model was employed to find risk factors for recurrent sickness absence by analyzing variables including demographic, work-related and work environmental factors. RESULTS: Of 540 study subjects, 200 employees (37.0 %) experienced recurrent sickness absence due to depression after RTW within the follow-up period. Higher organizational job demand evaluated by the Brief Job Stress Questionnaire (BJSQ) was found to be a risk factor (OR 1.46, 95 % CI 1.01-2.10) for recurrent sickness absence due to depression adjusted for confounding factors. CONCLUSIONS: High organizational job demand (evaluated by BJSQ) is a risk factor for recurrent sickness absence due to depression after RTW.

Nanotopography drives stem cell fate toward osteoblast differentiation through α1ß1 integrin signaling pathway.

The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2 SO4 /H2 O2 to yield nanotopography and rat MSCs were cultured under osteogenic and non-osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both osteogenic and non-osteogenic conditions. Additionally, the gene expression of α1 and ß1 integrins was higher in cells grown on Ti with nanotopography under non-osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1ß1 integrin inhibitor. These results indicate that α1ß1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface-mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration.