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In addition to a bulk energy gap, topological insulators accommodate a conducting, linearly dispersed Dirac surface state. This state is predicted to become massive if time reversal symmetry is broken, and to become insulating if the Fermi energy is positioned inside both the surface and bulk gaps. We introduced magnetic dopants into the three-dimensional topological insulator dibismuth triselenide (Bi₂Se₃) to break the time reversal symmetry and further position the Fermi energy inside the gaps by simultaneous magnetic and charge doping. The resulting insulating massive Dirac fermion state, which we observed by angle-resolved photoemission, paves the way for studying a range of topological phenomena relevant to both condensed matter and particle physics.

Manipulating the spins of the topological surface states represents an essential step towards exploring the exotic quantum states emerging from the time reversal symmetry breaking via magnetic doping or external magnetic fields. The latter case relies on the Zeeman effect and thereby we need to estimate the g -factor of the topological surface state precisely. Here, we report the direct observations of the Zeeman effect at the surfaces of Bi 2 Se 3 and Sb 2 Te 2 Se by spectroscopic-imaging scanning tunnelling microscopy. The Zeeman shift of the zero mode Landau level is identified unambiguously by appropriately excluding the extrinsic effects arising from the nonlinearity in the band dispersion of the topological surface state and the spatially varying potential. Surprisingly, the g -factors of the topological surface states in Bi 2 Se 3 and Sb 2 Te 2 Se are very different (+18 and −6, respectively). Such remarkable material dependence opens up a new route to control the spins of the topological surface states. The knowledge of how electrons behave under magnetic field provides inherent information for exotic quantum states. Here, Fu et al . find different g -factors of topological surface states in Bi 2 Se 3 and Sb 2 Te 2 Se, which suggests possible control of such states in spin-related applications.

Enhanced resistance to chemotherapy has been correlated with high levels of Delta-Np73 (DNp73), an anti-apoptotic protein of the p53 tumor-suppressor family which inhibits the pro-apoptotic members such as p53 and TAp73. Although genotoxic drugs have been shown to induce DNp73 degradation, lack of mechanistic understanding of this process precludes strategies to enhance the targeting of DNp73 and improve treatment outcomes. Antizyme (Az) is a mediator of ubiquitin-independent protein degradation regulated by the polyamine biosynthesis pathway. We show here that acetylpolyamine oxidase (PAOX), a catabolic enzyme of this pathway, upregulates DNp73 levels by suppressing its degradation via the Az pathway. Conversely, downregulation of PAOX activity by siRNA-mediated knockdown or chemical inhibition leads to DNp73 degradation in an Az-dependent manner. PAOX expression is suppressed by several genotoxic drugs, via selected members of the activator protein-1 (AP-1) transcription factors, namely c-Jun, JunB and FosB, which are required for stress-mediated DNp73 degradation. Finally, chemical- and siRNA-mediated inhibition of PAOX significantly reversed the resistant phenotype of DNp73-overexpressing cancer cells to genotoxic drugs. Together, these data define a critical mechanism for the regulation of DNp73 abundance, and reveal that inhibition of PAOX could widen the therapeutic index of cytotoxic drugs and overcome DNp73-mediated chemoresistance in tumors.

During orthodontic tooth movement, the activation of the vascular system in the compressed periodontal ligament (PDL) is an indispensable process in tissue remodeling. We hypothesized that compressive force would induce angiogenesis of PDL through the production of vascular endothelial growth factor (VEGF). We examined the localization of VEGF in rat periodontal tissues during experimental tooth movement in vivo, and the effects of continuous compressive force on VEGF production and angiogenic activity in human PDL cells in vitro. PDL cells adjacent to hyalinized tissue and alveolar bone on the compressive side showed marked VEGF immunoreactivity. VEGF mRNA expression and production in PDL cells increased, and conditioned medium stimulated tube formation. These results indicate that continuous compressive force enhances VEGF production and angiogenic activity in PDL cells, which may contribute to periodontal remodeling, including angiogenesis, during orthodontic tooth movement.

Osteosarcoma is the most common primary malignant bone tumor, and its standard treatment is a combination of surgery and chemotherapy. A poor response to chemotherapy causes unfavorable oncological outcomes. We investigated the correlation between osteoclast differentiation in biopsy specimens and the efficacy of neoadjuvant chemotherapy in resected specimens. Forty-nine patients who underwent neoadjuvant chemotherapy and subsequent surgical treatment at our institution between 1999 and 2018 were enrolled. Using medical records, we investigated the age, sex, tumor size, location, subtype, staging, chemotherapy agents (doxorubicin, cisplatin, ifosfamide, and methotrexate), number of neoadjuvant chemotherapy courses, number of osteoclasts in biopsy specimens, and efficacy of neoadjuvant chemotherapy according to the Rosen and Huvos classification (Grade I-IV) in resected specimens. Univariate and multivariate analyses were performed to identify factors predictive of a good response in resected specimens after neoadjuvant chemotherapy. A good response (Grade III/IV) was detected in 25, while a poor response (Grade I/II) was detected in 24. According to the multivariate analysis, ≥ 46 years old (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.01–0.45; p < 0.01) and ≥ 5 mature osteoclasts in a biopsy specimen (OR, 36.9; 95% CI, 6.03–225; p < 0.01) were significantly associated with the neoadjuvant chemotherapy efficacy. The accuracy for predicting a good response to chemotherapy based on ≥ 5 osteoclasts in a biopsy specimen in patients < 46 years old was 85%. The number of mature osteoclasts in biopsy specimens is a simple factor for predicting the efficacy of chemotherapy before treatment, although further studies will be required to determine the underlying mechanism.

We demonstrated 100 shots of burst laser irradiation with an Al target using a 1 kHz repetitive pulse laser. By using the laser, we generated ablation plasmas with a repetition rate of 1 kHz. The time-evolution of ion saturation current density in the generated ablation plasma was measured using the orifice probe. The result shows that the waveforms on 100 spikes were observed. The ion saturation current density decreased rapidly from the first to the third shot and reached a minimum value at the fourth shot. After the fourth shot, it reached 1 μA/mm 2 at the 53rd shot and settled at 0.5 μA/mm 2 . We extracted the time-evolution of ion saturation current densities of the first, 10th, 50th and 100th shots. The drift velocities were estimated by Time of Flight from the time-evolution of current. The result shows that the drift velocity of the ablation plasma increases with the increase in the number of shots.

The levels of polyamines (putrescine, spermidine and spermine) and polyamine oxidase in plasma of patients with chronic renal failure were determined. The level of putrescine was increased but the level of spermine was decreased in the plasma of these patients. The patients also had increased plasma polyamine oxidase activity leading to increased degradation of spermine. As acrolein was a major toxic compound produced from spermine by polyamine oxidase, the levels of free and protein-conjugated acrolein in plasma were also measured. Acrolein levels were enhanced in plasma of patients with chronic renal failure. The accumulated acrolein found as protein conjugates was equivalent to 170 µM, which was about 5-fold higher than in plasma of normal subjects. It was found that acrolein is mainly produced by spermine oxidase in plasma. An increase in putrescine, spermine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. After patients with chronic renal failure had undergone hemodialysis, their levels of plasma polyamines, spermine oxidase and acrolein returned towards normal. It is likely that acrolein produced from spermine accumulates in the blood due to decreased excretion into urine and may function as a uremic “toxin”.

During the period 22–28 July 2004, three geomagnetic storms occurred due to a sequence of coronal mass ejections. In this paper we present and discuss the ionospheric observations from a set of in situ satellites and ground‐based GPS total electron content and scintillation receivers, a VHF radar, and two chains of ionosondes (∼300°E and ∼120°E, respectively) that provide the evolutionary characteristics of equatorial and low‐latitude ionospheric irregularities versus longitude during these storm periods. It is found that the irregularities occurred over a wide longitudinal range, extending from around 300°E to 120°E on storm days 25 and 27 July 2004. On 25 July plasma bubbles (PBs) began premidnight in America and postmidnight in Southeast Asia. On 27 July the occurrence of irregularities followed the sunset terminator and was observed sequentially after sunset from American to Southeast Asian longitudes. Past studies have reported that storm‐time low‐latitude ionospheric irregularities are mostly confined to a narrower longitude range, <90°, after sunset hours and are associated with the prompt penetration of eastward electric fields (PPEFs) into low latitudes. In June solstice months the occurrence of range‐type spread F or PBs is very low in Southeast Asian and South American sectors. In contrast, the present results indicate that geomagnetic storms triggered the wide longitudinal development of PBs. In the American sector this was probably due to the effects of PPEFs on both storm days. However, in the Southeast Asian sector the PBs on the 2 days probably arose from disturbance dynamo electric field (DDEF), PPEF, and gravity wave seeding effects. This study further shows that under complex storm conditions, besides the long duration or multiple penetrations, the combined effects of PPEFs and DDEFs could result in a wide longitude extent of ionospheric irregularities at times.

The electrons associated with the conducting surface states of topological insulators are described by a two-component wavefunction. Experiments on Bi 2 Se 3 now show that the structure of Landau levels reflects this two-component nature. Massless Dirac electrons in condensed matter 1 , 2 , 3 , 4 , 5 , 6 are, unlike conventional electrons, described by two-component wavefunctions associated with the spin degrees of freedom in the surface state of topological insulators 5 , 6 . Hence, the ability to observe the two-component wavefunction is useful for exploring novel spin phenomena. Here we show that the two-component nature is manifest in Landau levels, the degeneracy of which is lifted by a Coulomb potential. Using spectroscopic-imaging scanning tunnelling microscopy, we visualize energy and spatial structures of Landau levels in Bi 2 Se 3 , a prototypical topological insulator. The observed Landau-level splitting and internal structures of Landau orbits are distinct from those in a conventional electron system 7 and are well reproduced by a two-component model Dirac Hamiltonian. Our model further predicts energy-dependent spin-magnetization textures in a potential variation and provides a way for manipulating spins in the topological surface state.

Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. M Tominaga , H Eguchi , H Manaka , K Igarashi , T Kato and A Sekikawa Department of Laboratory Medicine, Yamagata University School of Medicine, Japan. mtominag@med.id.yamagata-u.ac.jp Abstract OBJECTIVE: To determine whether the new category of impaired fasting glucose (IFG) recently proposed by the Expert Committee of the American Diabetes Association is a risk factor for cardiovascular disease. RESEARCH DESIGN AND METHODS: Death certificates and residence transfer documents from the cohort population consisting of participants of the diabetes prevalence study in Funagata, Yamagata prefecture, Japan, 1990-1992, were analyzed up through the end of 1996. First, the cohort population was classified into three groups: normal glucose tolerance (NGT) (n = 2,016), impaired glucose tolerance (IGT) (n = 382), and diabetic (n = 253). Then the same population was reclassified into normal fasting glucose (NFG), IFG, and diabetic. The cumulative survival rates among the groups were compared using the classical life-table method, and age-adjusted analyses, the person-year method, and Cox's proportional hazard model were adopted. RESULTS: At the end of seven observed years, the cumulative survival rates from cardiovascular disease of IGT and diabetes were 0.962 and 0.954, respectively, both significantly lower than that of NGT (0.988). The Cox's proportional hazard model analysis showed that the hazard ratio of IGT to NGT on death from cardiovascular disease was 2.219 (95% CI 1.076-4.577). However, the cumulative survival rate of IFG from cardiovascular disease was 0.977, not significantly lower than that of NFG (0.985). The Cox's hazard ratio of IFG to NFG on death from cardiovascular disease was 1.136 (0.345-3.734), which was not significant either. CONCLUSIONS: IGT was a risk factor for cardiovascular disease, but IFG was not.