306 research outputs found

    Memories of initial states and density imbalance in the dynamics of noninteracting and interacting disordered systems

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    We study the dynamics of one- and two-dimensional disordered lattice bosons/fermions initialized to a Fock state with 1 particle on a set of lattice sites (A) and 0 particles on the rest of the sites ((A) over bar). Such states have been considered in recent ultracold atomic experiments to detect many body localization. For noninteracting systems we establish a universal relation between the long time density imbalance between A and (A) over bar sites, I(infinity), the localization length xi(1), and the geometry of the initial pattern. For the alternating initial pattern of 1 and 0 particles in one dimension, I(infinity) = tanh[a/xi(l)], where a is the lattice spacing. For systems with mobility edge, we find analytic relations between I(infinity), the effective localization length (xi) over bar (l), and the fraction of localized states f(l). The imbalance as a function of disorder shows nonanalytic behavior when the mobility edge passes through a band edge. For interacting bosonic systems, we show that there is a mechanism to retain a finite long-time imbalance in the system even in presence of dissipative and stochastic processes coming from interparticle scattering. The scattering of particles, which lead to a decay of the memory of initial conditions through dissipative processes, also creates excitations in the system. For strong disorder, the excitations act as a local bath, whose noise correlators retain information of the initial pattern. This sustains a finite imbalance at long times in strongly disordered interacting systems

    Bott--Kitaev periodic table and index theory

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    We consider topological insulators and superconductors with discrete symmetries and clarify the relevant index theory behind the periodic table proposed by Kitaev. An effective Hamiltonian determines the analytical index, which can be computed by a topological index. We focus on the spatial dimensions one, two and three, and only consider the bulk theory. In two dimensions, the Z\mathbb{Z}-valued invariants are given by the first Chern number. Meanwhile, Z2\mathbb{Z}_2-valued invariants can be computed by the odd topological index and its variations. The Bott-Kitaev periodic table is well-known in the physics literature, we organize the topological invariants in the framework of KR-theory.Comment: 37 page

    Existing and Evolving Bioethical Dilemmas, Challenges, and Controversies in Vascularized Composite Allotransplantation: An International Perspective From the Brocher Bioethics Working Group

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    Early results of hand and face transplants and other grafts such as those of uterus, penis, trachea, larynx, or abdominal wall have confirmed the potential for vascularized composite allotransplantation (VCA) to restore appearance, anatomy, function, independence, and social integration in patients suffering from devastating tissue deficits untreatable by conventional treatment options. Despite such promise, these novel and complex procedures face challenges and controversies that remain open to discussion and debate. Indeed, many barriers to clinical advancement and negative stakeholder perceptions still exist. The bioethical challenges surrounding VCA include but are not limited to justice and vulnerability of subjects, and their experiences with risks, benefits and outcomes, provider economy of fame, public awareness and attitudes toward transplantation, and policy and regulatory issues shaping progress of the field. The First International Workshop on Bioethical Challenges in Reconstructive Transplantation was organized by the Brocher Foundation in Hermance, Switzerland. VCA professionals representing teams from across the world examined bioethical issues in VCA related to standards for safety, efficacy, feasibility, privacy, confidentiality, and equitability. Key discussion topics from the workshop were included in a survey questionnaire implemented across VCA professionals attending the 13th Congress of International Society of VCA held in Salzburg, Austria. The insights from the Brocher workshop and International Society of VCA survey as presented here could help inform the future development of clinical practice and policy strategies in VCA to ensure value, accessibility, and acceptance of these procedures by potential donors, potential or actual recipients and their families, and providers and payers

    Interface driven magnetoelectric effects in granular CrO2

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    Antiferromagnetic and magnetoelectric Cr2O3-surfaces strongly affect the electronic properties in half metallic CrO2. We show the presence of a Cr2O3 surface layer on CrO3 grains by high-resolution transmission electron microscopy. The effect of these surface layers is demonstrated by measurements of the temperature variation of the magnetoelectric susceptibility. A major observation is a sign change at about 100 K followed by a monotonic rise as a function of temperature. These electric field induced moments in CrO3 are correlated with the magnetoelectric susceptibility of pure Cr2O3. This study indicates that it is important to take into account the magnetoelectric character of thin surface layers of Cr2O3 in granular CrO2 for better understanding the transport mechanism in this system. The observation of a finite magnetoelectric susceptibility near room temperature may find utility in device applications.Comment: Figure 1 with strongly reduced resolutio

    Identification of stress-responsive genes in an indica rice (Oryza sativa L.) using ESTs generated from drought-stressed seedlings

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    The impacts of drought on plant growth and development limit cereal crop production worldwide. Rice (Oryza sativa) productivity and production is severely affected due to recurrent droughts in almost all agroecological zones. With the advent of molecular and genomic technologies, emphasis is now placed on understanding the mechanisms of genetic control of the drought-stress response. In order to identify genes associated with water-stress response in rice, ESTs generated from a normalized cDNA library, constructed from drought-stressed leaf tissue of an indica cultivar, Nagina 22 were used. Analysis of 7794 cDNA sequences led to the identification of 5815 rice ESTs. Of these, 334 exhibited no significant sequence homology with any rice ESTs or full-length cDNAs in public databases, indicating that these transcripts are enriched during drought stress. Analysis of these 5815 ESTs led to the identification of 1677 unique sequences. To characterize this drought transcriptome further and to identify candidate genes associated with the drought-stress response, the rice data were compared with those for abiotic stress-induced sequences obtained from expression profiling studies in Arabidopsis, barley, maize, and rice. This comparative analysis identified 589 putative stress-responsive genes (SRGs) that are shared by these diverse plant species. Further, the identified leaf SRGs were compared to expression profiles for a drought-stressed rice panicle library to identify common sequences. Significantly, 125 genes were found to be expressed under drought stress in both tissues. The functional classification of these 125 genes showed that a majority of them are associated with cellular metabolism, signal transduction, and transcriptional regulation

    Loss of neuronal integrity during progressive HIV-1 infection of humanized mice.

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    Neuronal damage induced by ongoing human immunodeficiency virus type 1 (HIV-1) infection was investigated in humanized NOD/scid-IL-2Rγ(c)(null) mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4(+) T-cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and fluorescence emission, showed regional reduction of neuronal soma and synaptic architectures. This was evidenced by loss of microtubule-associated protein 2, synaptophysin, and neurofilament antigens. This study is the first, to our knowledge, demonstrating lost neuronal integrity after HIV-1 infection in humanized mice. As such, the model permits studies of the relationships between ongoing viral replication and virus-associated neurodegeneration

    Afatinib and Temozolomide Combination Inhibits Tumorigenesis by Targeting EGFRvIII-cMet Signaling in Glioblastoma Cells

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    BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor with universal recurrence and poor prognosis. The recurrence is largely driven by chemoradiation resistant cancer stem cells (CSCs). Epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are amplified in ~ 60% and ~ 30% of GBM patients, respectively; however, therapies targeting EGFR have failed to improve disease outcome. EGFRvIII-mediated cross-activation of tyrosine kinase receptor, cMET, regulates GBM CSC maintenance and promote tumor recurrence. Here, we evaluated the efficacy of pan-EGFR inhibitor afatinib and Temozolomide (TMZ) combination on GBM in vitro and in vivo. METHODS: We analyzed the effect of afatinib and temozolomide (TMZ) combination on GBM cells U87MG and U251 engineered to express wild type (WT) EGFR, EGFRvIII or EGFRvIII dead kinase, CSCs isolated from U87 and U87EGFRvIII in vitro. The therapeutic utility of the drug combination was investigated on tumor growth and progression using intracranially injected U87EGFRvIII GBM xenografts. RESULTS: Afatinib and TMZ combination synergistically inhibited the proliferation, clonogenic survival, motility, invasion and induced senescence of GBM cells compared to monotherapy. Mechanistically, afatinib decreased U87EGFRvIII GBM cell proliferation and motility/invasion by inhibiting EGFRvIII/AKT, EGFRvIII/JAK2/STAT3, and focal adhesion kinase (FAK) signaling pathways respectively. Interestingly, afatinib specifically inhibited EGFRvIII-cMET crosstalk in CSCs, resulting in decreased expression of Nanog and Oct3/4, and in combination with TMZ significantly decreased their self-renewal property in vitro. More interestingly, afatinib and TMZ combination significantly decreased the xenograft growth and progression compared to single drug alone. CONCLUSION: Our study demonstrated significant inhibition of GBM tumorigenicity, CSC maintenance in vitro, and delayed tumor growth and progression in vivo by combination of afatinib and TMZ. Our results warrant evaluation of this drug combination in EGFR and EGFRvIII amplified GBM patients

    Sensitization and desensitization of burn patients as potential candidates for vascularized composite allotransplantation

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    Sensitization describes the acquired ability of the immune system to react to foreign human leukocyte antigens (HLA) by producing antibodies and developing memory cells. In the field of transplantation, recipient preformed HLA antibodies due to previous sensitization have been identified - beneath ABO incompatibility - as a major factor for acute graft rejection. Several reasons for sensitization have largely been studied, such as previous blood transfusions, pregnancies or former transplants. Recent studies indicate that the use of assist devices (e.g. ECMO) or cadaveric skin allotransplantation providing temporary coverage in burn patients may lead to additional sensitization. As vascularized composite allotransplantation (VCA) has become a rapidly advancing therapeutic option for reconstruction of complex tissue defects in burns, it seems even more important to become familiar with immunological principles and to be cautiously aware of both sources of sensitization and therapeutic concepts in burns avoiding sensitization. This may also include emergency VCAs in burn patients as potential strategy for early definitive reconstruction avoiding procedures triggering HLA antibody formation. We hereby provide an overview on current evidence in the field of pre- and peritrans-plant sensitization, followed by posttransplant strategies of desensitization and their potential impact on future treatments of burn patients. (C) 2015 Elsevier Ltd and ISBI. All rights reserved.Peer reviewe

    Preliminary Studies on Immune Response and Viral Pathogenesis of Zika Virus in Rhesus Macaques

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    Zika Virus (ZIKV) is primarily transmitted through mosquito bites. It can also be transmitted during sexual intercourse and in utero from mother to fetus. To gain preliminary insight into ZIKV pathology and immune responses on route of transmission, rhesus macaques (RMs) were inoculated with ZIKV (PRVABC59) via intravaginal (IVAG) (n = 3) or subcutaneous (sub Q) (n = 2) routes. Systemic ZIKV infection was observed in all RMs, regardless of the route of inoculation. After 9 days postinfection (dpi), ZIKV was not detected in the plasma of IVAG- and sub-Q-inoculated RMs. Importantly, RMs harbored ZIKV up to 60 dpi in various anatomical locations. Of note, ZIKV was also present in several regions of the brain, including the caudate nucleus, parietal lobe, cortex, and amygdala. These observations appear to indicate that ZIKV infection may be systemic and persistent regardless of route of inoculation. In addition, we observed changes in key immune cell populations in response to ZIKV infection. Importantly, IVAG ZIKV infection of RMs is associated with increased depletion of CD11C hi myeloid cells, reduced PD-1 expression in NK cells, and elevated frequencies of Ki67⁺ CD8⁺ central memory cells as compared to sub Q ZIKV-infected RMs. These results need to interpreted with caution due to the small number of animals utilized in this study. Future studies involving large groups of animals that have been inoculated through both routes of transmission are needed to confirm our findings
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