Electronic signature of the vacancy ordering in NbO (Nb3O3)

We investigated the electronic structure of the vacancy-ordered 4d-transition metal monoxide NbO (Nb3O3) using angle-integrated soft- and hard-x-ray photoelectron spectroscopy as well as ultra-violet angle-resolved photoelectron spectroscopy. We found that density-functional-based band structure calculations can describe the spectral features accurately provided that self-interaction effects are taken into account. In the angle-resolved spectra we were able to identify the so-called vacancy band that characterizes the ordering of the vacancies. This together with the band structure results indicates the important role of the very large inter-Nb-4d hybridization for the formation of the ordered vacancies and the high thermal stability of the ordered structure of niobium monoxide

Effects of TGF-β1 and IGF-1 on proliferation of human nucleus pulposus cells in medium with different serum concentrations

BACKGROUND: The low proliferative viability of human nucleus pulposus(NP) cells is considered as a cause of intervertebral discs degeneration. Growth factors, such as TGF-β1 and IGF-1, have been implicated in cell proliferation and matrix synthesis. OBJECTIVE: To investigate the dose-response and time-course effect of transforming growth factorβ1(TGF-β1) and insulin-like growth factor-1(IGF-1) on proliferation of NP cells. STUDY DESIGN: 3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) is reduced by dehydrogenase in mitochondria of live cells. The proliferative viability of cells corresponds to the amount of MTT reduced, which is measured with an enzyme-linked immunosorbent assay plate reader. In this study, we assessed dose- and time-dependent effects of NP cells to TGF-β1 and IGF-1 in medium with different serum concentrations by MTT assay. METHODS: After release of informed consent, tissue samples of NP were obtained from anterior surgical procedures performed on five donors with idiopathic scoliosis. Isolated cells were cultured in F12 medium supplemented with 10% fetal bovine serum(FBS). Cells were seeded in 96-well plates at 1 × 10(3 )cells/well. After synchronization, medium was replaced by F12 containing 1% or 10% FBS with either single or combination of TGF-β1 and IGF-1. Dose-response and time-course effect were examined by MTT assay. RESULTS: In the presence of 1% FBS, the response to IGF-1 was less striking, whereas TGF-β1 had a remarkably stimulating effect on cell proliferation. In 10% FBS, both of the two growth factors had statistical significant mitogenic effects, especially TGF-β1. The dose-dependent effect of TGF and IGF on cell proliferation was found within different concentrations of each growth factor(TGF-β1 1–10 μg/L, IGF-1 10–100 μg/L). The time-course effect showed a significant elevation three days later. CONCLUSION: TGF-β1 and IGF-1 were efficient to stimulate cell proliferation of human NP cells in vitro with a dose- and time-dependent manner. These results support the therapeutic potentials of the two growth factors in the treatment of disc degeneration

Reliability, validity, and responsiveness of the Japanese version of the Neck Pain and Disability Scale

Abstract Background Until recently, no Japanese versions have existed of the more popular, patient-reported disability questionnaires for neck pain. This study aimed to test the reliability, validity, and responsiveness of the Japanese version of the Neck Pain and Disability Scale (NPDS), one of the most widely used questionnaires in patients with neck pain. Methods In this validation study, 167 outpatients with neck pain participated. Patients received the NPDS and the Medical Outcome Study Short Form 36-item Health Survey (SF-36), and used Visual Analog Scales (VASs) to assess pain and global health. To examine test-retest reliability, patients who were considered stable by clinicians were given the NPDS 2 weeks after baseline. To examine responsiveness, patients who had not undergone treatment at the time of the first data collection or had no change in treatment over 3 months were studied again 2 weeks after starting a new medication or physical therapy. Results Of the 167 participants, 143 completed the questionnaires (85.6%). Factor analysis showed two factors, defined as neck-pain-related disability (factor 1) and neck-related pain (factor 2). Cronbach's a coefficient for factor 1, factor 2, and total score was 0.94, 0.93, and 0.96. The intra-class correlation coefficients for the 19 more stable patients were 0.79, 0.88, and 0.87. For concurrent validity, the correlation between NPDS subscales and total score and SF-36 subscale scores ranged from r = -0.54 to -0.22 (p \ 0.01). Correlations between the NPDS subscales and total score and VAS of pain ranged from 0.56 to 0.77 (p \ 0.01) and those for VAS of global health ranged from 0.48 to 0.63 (p \ 0.01). The NPDS subscales and total scores of the 41 patients retested after treatment were significantly improved. Electronic supplementary material The online version of this articl

Charge-transfer energy in iridates: A hard x-ray photoelectron spectroscopy study

We have investigated the electronic structure of iridates in the double perovskite crystal structure containing either Ir4+ or Ir5+ using hard x-ray photoelectron spectroscopy. The experimental valence band spectra can be well reproduced using tight-binding calculations including only the Ir 5d, O 2p, and O 2s orbitals with parameters based on the downfolding of the density-functional band structure results. We found that, regardless of the A and B cations, the A2BIrO6 iridates have essentially zero O 2p to Ir 5d charge-transfer energies. Hence double perovskite iridates turn out to be extremely covalent systems with the consequence being that the magnetic exchange interactions become very long ranged, thereby hampering the materialization of the long-sought Kitaev physics. Nevertheless, it still would be possible to realize a spin-liquid system using the iridates with a proper tuning of the various competing exchange interactions

CaCu3Ru4O12: a high-kondo-temperature transition-metal oxide

遷移金属酸化物の近藤効果を初めて実証 --電子相関物性の設計・探索の新たなプラットホームを開拓--. 京都大学プレスリリース. 2022-01-31.Open access publication funded by the Max Planck Society.We present a comprehensive study of CaCu₃Ru₄O₁₂ using bulk sensitive hard and soft x-ray spectroscopy combined with local-density approximation + dynamical mean-field theory (DMFT) calculations. Correlation effects on both the Cu and Ru ions can be observed. From the Cu 2p core-level spectra, we deduce the presence of magnetic Cu²⁺ ions hybridized with a reservoir of itinerant electrons. The strong photon energy dependence of the valence band allows us to disentangle the Ru, Cu, and O contributions and, thus, to optimize the DMFT calculations. The calculated spin and charge susceptibilities show that the transition metal oxide CaCu₃Ru₄O₁₂ must be classified as a Kondo system and that the Kondo temperature is in the range of 500–1000 K

Synergistic Interactions between the NS3hel and E Proteins Contribute to the Virulence of Dengue Virus Type 1

Dengue virus constitutes a significant public health problem in tropical regions of the world. Despite the high morbidity and mortality of this infection, no effective antiviral drugs or vaccines are available for the treatment or prevention of dengue infections. The profile of clinical signs associated with dengue infection has changed in recent years with an increase in the number of episodes displaying unusual signs. We use reverse genetics technology to engineer DENV-1 viruses with subsets of mutations previously identified in highly neurovirulent strains to provide insights into the molecular mechanisms underlying dengue neuropathogenesis. We found that single mutations affecting the E and NS3hel proteins, introduced in a different genetic context, had a synergistic effect increasing DENV replication capacity in human and mosquito derived cells in vitro. We also demonstrated correlations between the presence of these mutations and viral replication efficiency, viral loads, the induction of innate immune response genes and pathogenesis in a mouse model. These results should improve our understanding of the DENV-host cell interaction and contribute to the development of effective antiviral strategies

Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges

Lumbar discectomy is a very effective therapy for neurological decompression in patients suffering from sciatica due to hernia nuclei pulposus. However, high recurrence rates and persisting post-operative low back pain in these patients require serious attention. In the past decade, tissue engineering strategies have been developed mainly targeted to the regeneration of the nucleus pulposus (NP) of the intervertebral disc. Accompanying techniques that deal with the damaged annulus fibrous are now increasingly recognised as mandatory in order to prevent re-herniation to increase the potential of NP repair and to confine NP replacement therapies. In the current review, the requirements, achievements and challenges in this quickly emerging field of research are discussed

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems

NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma

The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and its downstream effector responses. Uncovering the hidden downstream effectors can aid in understanding melanoma biology and improve targeted therapy efficacy. The inflammasome sensor, NACHT, LRR, and PYD domains-containing protein 1 (NLRP1), is responsible for IL-1β maturation and itself is a melanoma tumor promoter. Here, we report that NLRP1 is a downstream effector of MAPK/ERK signaling through the activating transcription factor 4 (ATF4), creating regulation in metastatic melanoma cells. We confirmed that the NLRP1 gene is a target of ATF4. Interestingly, ATF4/NLRP1 regulation by the MAPK/ERK pathway uses distinct mechanisms in melanoma cells before and after the acquired resistance to targeted therapy. In parental cells, ATF4/NLRP1 is regulated by the MAPK/ERK pathway through the ribosomal S6 kinase 2 (RSK2). However, vemurafenib (VEM) and trametinib (TRA)-resistant cells lose the signaling via RSK2 and activate the cAMP/protein kinase A (PKA) pathway to redirect ATF4/NLRP1. Therefore, NLRP1 expression and IL-1β secretion were downregulated in response to VEM and TRA in parental cells but enhanced in drug-resistant cells. Lastly, silencing NLRP1 in drug-resistant cells reduced their cell growth and inhibited colony formation. In summary, we demonstrated that NLRP1 functions downstream of the MAPK/ERK signaling via ATF4 and is a player of targeted therapy resistance in melanoma. Targeting NLRP1 may improve the therapeutic efficacy of targeted therapy in melanoma