113 research outputs found

    A SM-like Higgs near 125 GeV in low energy SUSY: a comparative study for MSSM and NMSSM

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    Motivated by the recent LHC hints of a Higgs boson around 125 GeV, we assume a SM-like Higgs with the mass 123-127 GeV and study its implication in low energy SUSY by comparing the MSSM and NMSSM. We consider various experimental constraints at 2-sigma level (including the muon g-2 and the dark matter relic density) and perform a comprehensive scan over the parameter space of each model. Then in the parameter space which is allowed by current experimental constraints and also predicts a SM-like Higgs in 123-127 GeV, we examine the properties of the sensitive parameters (like the top squark mass and the trilinear coupling A_t) and calculate the rates of the di-photon signal and the VV^* (V=W,Z) signals at the LHC. Our typical findings are: (i) In the MSSM the top squark and A_t must be large and thus incur some fine-tuning, which can be much ameliorated in the NMSSM; (ii) In the MSSM a light stau is needed to enhance the di-photon rate of the SM-like Higgs to exceed its SM prediction, while in the NMSSM the di-photon rate can be readily enhanced in several ways; (iii) In the MSSM the signal rates of pp -> h -> VV^* at the LHC are never enhanced compared with their SM predictions, while in the NMSSM they may get enhanced significantly; (iv) A large part of the parameter space so far survived will be soon covered by the expected XENON100(2012) sensitivity (especially for the NMSSM).Comment: Version in JHEP (refs added

    Bisphosphonates Cause Osteonecrosis of the Jaw-Like Disease in Mice

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    Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a morbid bone disease linked to long-term bisphosphonate use. Despite its broad health impact, mechanistic study is lacking. In this study, we have established a mouse model of BONJ-like disease based on the equivalent clinical regimen in myeloma patients, a group associated with high risk of BONJ. We demonstrate that the murine BONJ-like disease recapitulates major clinical and radiographical manifestations of the human disease, including characteristic features of osseous sclerosis, sequestra, avascular, and radiopaque alveolar bone in the jaw that persists beyond a normal course of wound healing following tooth extraction. We find that long-term administration of bisphosphonates results in an increase in the size and number of osteoclasts and the formation of giant osteoclast-like cells within the alveolar bone. We show that the development of necrotic bone and impaired soft tissue healing in our mouse model is dependent on long-term use of high-dose bisphosphonates, immunosuppressive and chemotherapy drugs, as well as mechanical trauma. Most importantly, we demonstrate that bisphosphonate is the major cause of BONJ-like disease in mice, mediated in part by its ability to suppress osseous angiogenesis and bone remodeling. The availability of this novel mouse model of BONJ-like disease will help elucidate the pathophysiology of BONJ and ultimately develop novel approaches for prevention and treatment of human BONJ. Copyright © American Society for Investigative Pathology

    Mesenchymal Stem Cell-Mediated Ectopic Hematopoiesis Alleviates Aging-Related Phenotype in Immunocompromised Mice

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    Subcutaneous transplants of bone marrow mesenchymal stem cells (BMMSCs) are capable of generating ectopic bone and organizing functional hematopoietic marrow elements in animal models. Here we report that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate as a carrier suppressed age- related degeneration in multiple organs and benefited an increase in life span extension compared with control litter- mates. The newly organized ectopic bone/ marrow system restores active hemato-poiesis via the erythropoietin receptor/ signal transducer and activator of transcription 5 (Stat5) pathway. Furthermore, the BMMSC recipient mice showed elevated level of Klotho and suppression of insulin-like growth factor I signaling, which may be the mechanism contributing to the alleviation of aging-like pheno-types and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hema-topoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice. © 2009 by The American Society of Hematology

    Farey tree locking of terahertz semiconductor laser frequency combs

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    Frequency combs show various applications in molecular fingerprinting, imaging, communications, and so on. In the terahertz frequency range, semiconductor-based quantum cascade lasers (QCLs) are ideal platforms for realizing the frequency comb operation. Although self-started frequency comb operation can be obtained in free-running terahertz QCLs due to the four-wave mixing locking effects, resonant/off-resonant microwave injection, phase locking, and femtosecond laser based locking techniques have been widely used to broaden and stabilize terahertz QCL combs. These active locking methods indeed show significant effects on the frequency stabilization of terahertz QCL combs, but they simultaneously have drawbacks, such as introducing large phase noise and requiring complex optical coupling and/or electrical circuits. Here, we demonstrate Farey tree locking of terahertz QCL frequency combs under microwave injection. The frequency competition between the Farey fraction frequency and the cavity round-trip frequency results in the frequency locking of terahertz QCL combs, and the Farey fraction frequencies can be accurately anticipated based on the downward trend of the Farey tree hierarchy. Furthermore, dual-comb experimental results show that the phase noise of the dual-comb spectral lines is significantly reduced by employing the Farey tree locking method. These results pave the way to deploying compact and low phase noise terahertz frequency comb sources.Comment: 22 page, 7 figure

    Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents

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    Background: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels. Methods and Findings: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studied revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)-induced osteoporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density. Conclusion: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts. © 2008 Yamaza et al

    The 2021 room-temperature superconductivity roadmap.

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    Designing materials with advanced functionalities is the main focus of contemporary solid-state physics and chemistry. Research efforts worldwide are funneled into a few high-end goals, one of the oldest, and most fascinating of which is the search for an ambient temperature superconductor (A-SC). The reason is clear: superconductivity at ambient conditions implies being able to handle, measure and access a single, coherent, macroscopic quantum mechanical state without the limitations associated with cryogenics and pressurization. This would not only open exciting avenues for fundamental research, but also pave the road for a wide range of technological applications, affecting strategic areas such as energy conservation and climate change. In this roadmap we have collected contributions from many of the main actors working on superconductivity, and asked them to share their personal viewpoint on the field. The hope is that this article will serve not only as an instantaneous picture of the status of research, but also as a true roadmap defining the main long-term theoretical and experimental challenges that lie ahead. Interestingly, although the current research in superconductor design is dominated by conventional (phonon-mediated) superconductors, there seems to be a widespread consensus that achieving A-SC may require different pairing mechanisms.In memoriam, to Neil Ashcroft, who inspired us all

    Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents

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    Background: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels. Methods and Findings: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studies revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)- induced ostoeporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density. Conclusion: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts.Takayoshi Yamaza, Yasuo Miura, Yanming Bi, Yongzhong Liu, Kentaro Akiyama, Wataru Sonoyama, Voymesh Patel, Silvio Gutkind, Marian Young, Stan Gronthos, Anh Le, Cun-Yu Wang, WanJun Chen and Songtao Sh

    Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia

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    Background: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. Objective: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. Methods: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12–75 years with severe asthma receiving medium- to high-dose inhaled corticosteroid/long-acting β2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1 is being defined, not BD, which has already been defined) and total asthma symptom score (TASS). Safety was evaluated ≤Week 56. Results: Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p <0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p <0.0001) and TASS (LSD −0.25 [−0.45, −0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. Conclusions: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results
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