13 results on '"M Lebeau"'
Search Results
2. Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography
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Obinna C. Ubah, Eric W. Lake, Gihan S. Gunaratne, Joseph P. Gallant, Marie Fernie, Austin J. Robertson, Jonathan S. Marchant, Tyler D. Bold, Ryan A. Langlois, William E. Matchett, Joshua M. Thiede, Ke Shi, Lulu Yin, Nicholas H. Moeller, Surajit Banerjee, Laura Ferguson, Marina Kovaleva, Andrew J. Porter, Hideki Aihara, Aaron M. LeBeau, and Caroline J. Barelle
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Science - Abstract
Shark antibodies (Variable New Antigen Receptors, VNARs) are the smallest naturally occurring antibody fragments. Here, the authors screen a VNAR phage display library against the SARS-CoV2 receptor binding domain (RBD) and identify VNARs that neutralize the SARSCoV-2 virus and discuss their mechanisms of viral neutralization.
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- 2021
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3. An antisite defect mechanism for room temperature ferroelectricity in orthoferrites
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Shuai Ning, Abinash Kumar, Konstantin Klyukin, Eunsoo Cho, Jong Heon Kim, Tingyu Su, Hyun-Suk Kim, James M. LeBeau, Bilge Yildiz, and Caroline A. Ross
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Science - Abstract
Ferroelectricity in orthoferrite perovskites has stimulated intense research, but the mechanism remains unclear. Here, the authors propose an antisite defect mechanism for introducing ferroelectricity in magnetically ordered YFeO3 and the family of rare earth orthoferrites.
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- 2021
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4. Direct imaging and electronic structure modulation of moiré superlattices at the 2D/3D interface
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Kate Reidy, Georgios Varnavides, Joachim Dahl Thomsen, Abinash Kumar, Thang Pham, Arthur M. Blackburn, Polina Anikeeva, Prineha Narang, James M. LeBeau, and Frances M. Ross
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Science - Abstract
Here, advanced scanning transmission electron microscopy techniques are used to image the atomic structure at the interface between 2D MoS2 and 3D Au nanoislands, revealing a moiré superlattice and illustrating the potential for (opto-)electronic moiré engineering at the 2D/3D interface.
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- 2021
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5. Thickness and temperature dependence of the atomic-scale structure of SrRuO3 thin films
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Xuanyi Zhang, Aubrey N. Penn, Lena Wysocki, Zhan Zhang, Paul H. M. van Loosdrecht, Lior Kornblum, James M. LeBeau, Ionela Lindfors-Vrejoiu, and Divine P. Kumah
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Biotechnology ,TP248.13-248.65 ,Physics ,QC1-999 - Abstract
The temperature-dependent layer-resolved structure of 3 to 44 unit cell thick SrRuO3 (SRO) films grown on Nb-doped SrTiO3 substrates is investigated using a combination of high-resolution synchrotron x-ray diffraction and high-resolution electron microscopy to understand the role that structural distortions play in suppressing ferromagnetism in ultra-thin SRO films. The oxygen octahedral tilts and rotations and Sr displacements characteristic of the bulk orthorhombic phase are found to be strongly dependent on temperature, the film thickness, and the distance away from the film–substrate interface. For thicknesses, t, above the critical thickness for ferromagnetism (t > 3 uc), the orthorhombic distortions decrease with increasing temperature above TC. Below TC, the structure of the films remains constant due to the magneto-structural coupling observed in bulk SRO. The orthorhombic distortions are found to be suppressed in the 2–3 interfacial layers due to structural coupling with the SrTiO3 substrate and correlate with the critical thickness for ferromagnetism in uncapped SRO films.
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- 2022
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6. On the redistribution of charge in La0.7Sr0.3CrO3/La0.7Sr0.3MnO3 multilayer thin films
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Aubrey N. Penn, Sanaz Koohfar, Divine P. Kumah, and James M. LeBeau
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Physics ,QC1-999 - Abstract
The atomic and electronic structures of La0.7Sr0.3MnO3 (LSMO)/La0.7Sr0.3CrO3 (LSCO) multilayer thin films are investigated using aberration corrected scanning transmission electron microscopy (STEM) imaging and spectroscopy. Atomic resolution high angle annular dark-field reveals that LSMO layers have an expanded out-of-plane lattice parameter compared to compressed LSCO layers, contrasting with x-ray diffraction measurements. The expansion is found to result from preferential oxygen vacancy formation in LSMO during STEM sample preparation as determined by electron energy-loss spectroscopy. The La/Sr atom column intensity is also found to oscillate by about 4% between the LSMO and LSCO layers, indicative of La/Sr concentration variation. Using energy-dispersive x-ray spectroscopy in combination with image simulations, we confirm the La/Sr inhomogeneity and elucidate the origin of charge redistribution within the multilayer. These results illuminate the sensitivity of the technique to subtle structural, chemical, and electronic features that can arise to compensate charge imbalances in complex oxide heterostructures.
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- 2020
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7. Electrostatic potential and valence modulation in La0.7Sr0.3MnO3 thin films
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Robbyn Trappen, A. C. Garcia-Castro, Vu Thanh Tra, Chih-Yeh Huang, Wilfredo Ibarra-Hernandez, James Fitch, Sobhit Singh, Jinling Zhou, Guerau Cabrera, Ying-Hao Chu, James M. LeBeau, Aldo H. Romero, and Mikel B. Holcomb
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Surface Valence ,Expected Bulk Value ,LSMO Layers ,Thin Film LSMO ,Polar Catastrophe ,Medicine ,Science - Abstract
Abstract The Mn valence in thin film La0.7Sr0.3MnO3 was studied as a function of film thickness in the range of 1–16 unit cells with a combination of non-destructive bulk and surface sensitive X-ray absorption spectroscopy techniques. Using a layer-by-layer valence model, it was found that while the bulk averaged valence hovers around its expected value of 3.3, a significant deviation occurs within several unit cells of the surface and interface. These results were supported by first principles calculations. The surface valence increases to up to Mn3.7+, whereas the interface valence reduces down to Mn2.5+. The change in valence from the expected bulk value is consistent with charge redistribution due to the polar discontinuity at the film-substrate interface. The comparison with theory employed here illustrates how this layer-by-layer valence evolves with film thickness and allows for a deeper understanding of the microscopic mechanisms at play in this effect. These results offer insight on how the two-dimensional electron gas is created in thin film oxide alloys and how the magnetic ordering is reduced with dimensionality.
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- 2018
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8. The role of CD133 in cancer: a concise review
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Paige M. Glumac and Aaron M. LeBeau
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Cancer stem cells ,CD133 ,Cancer ,Prognosis ,Immunotherapeutic ,Medicine (General) ,R5-920 - Abstract
Abstract Despite the abundant ongoing research efforts, cancer remains one of the most challenging diseases to treat globally. Due to the heterogenous nature of cancer, one of the major clinical challenges in therapeutic development is the cancer’s ability to develop resistance. It has been hypothesized that cancer stem cells are the cause for this resistance, and targeting them will lead to tumor regression. A pentaspan transmembrane glycoprotein, CD133 has been suggested to mark cancer stem cells in various tumor types, however, the accuracy of CD133 as a cancer stem cell biomarker has been highly controversial. There are numerous speculations for this, including differences in cell culture conditions, poor in vivo assays, and the inability of current antibodies to detect CD133 variants and deglycosylated epitopes. This review summarizes the most recent and relevant research regarding the controversies surrounding CD133 as a normal stem cell and cancer stem cell biomarker. Additionally, it aims to establish the overall clinical significance of CD133 in cancer. Recent clinical studies have shown that high expression of CD133 in tumors has been indicated as a prognostic marker of disease progression. As such, a spectrum of immunotherapeutic strategies have been developed to target these CD133pos cells with the goal of translation into the clinic. This review compiles the current therapeutic strategies targeting CD133 and discusses their prognostic potential in various cancer subtypes.
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- 2018
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9. The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach
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Shilvi Joshi, Lang Chen, Michael B. Winter, Yi-Lun Lin, Yang Yang, Mariya Shapovalova, Paige M. Smith, Chang Liu, Fang Li, and Aaron M. LeBeau
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Medicine ,Science - Abstract
Abstract The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1–P4′ amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.
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- 2017
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10. Structural Characterization of a Minimal Antibody against Human APOBEC3B
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Heng Tang, Özlem Demir, Fredy Kurniawan, William L. Brown, Ke Shi, Nicholas H. Moeller, Michael A. Carpenter, Christopher Belica, Kayo Orellana, Guocheng Du, Aaron M. LeBeau, Rommie E. Amaro, Reuben S. Harris, and Hideki Aihara
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APOBEC3B ,antiviral innate immunity ,cancer mutagenesis ,crystal structure ,DNA cytosine deaminase ,molecular dynamics simulation ,Microbiology ,QR1-502 - Abstract
APOBEC3B (A3B) is one of seven human APOBEC3 DNA cytosine deaminases that restrict viral infections as part of the overall innate immune response, but it also plays a major role in tumor evolution by mutating genomic DNA. Given the importance of A3B as a restriction factor of viral infections and as a driver of multiple human cancers, selective antibodies against A3B are highly desirable for its specific detection in various research and possibly diagnostic applications. Here, we describe a high-affinity minimal antibody, designated 5G7, obtained via a phage display screening against the C-terminal catalytic domain (ctd) of A3B. 5G7 also binds APOBEC3A that is highly homologous to A3Bctd but does not bind the catalytic domain of APOBEC3G, another Z1-type deaminase domain. The crystal structure of 5G7 shows a canonical arrangement of the heavy and light chain variable domains, with their complementarity-determining region (CDR) loops lining an antigen-binding cleft that accommodates a pair of α-helices. To understand the mechanism of A3Bctd recognition by 5G7, we used the crystal structures of A3Bctd and 5G7 as templates and computationally predicted the A3B-5G7 complex structure. Stable binding poses obtained by the simulation were further tested by site-directed mutagenesis and in vitro binding analyses. These studies mapped the epitope for 5G7 to a portion of C-terminal α6 helix of A3Bctd, with Arg374 playing an essential role. The same region of A3Bctd was used previously as a peptide antigen for generating a rabbit monoclonal antibody (mAb 5210-87-13), suggesting that this region is particularly immunogenic and that these antibodies from very different origins may share similar binding modes. Our studies provide a platform for the development of selective antibodies against A3B and other APOBEC3 family enzymes.
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- 2021
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11. The Molecular Imaging of Natural Killer Cells
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Mariya Shapovalova, Sean R. Pyper MD, PhD, Branden S. Moriarity PhD, and Aaron M. LeBeau PhD
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Biology (General) ,QH301-705.5 ,Medical technology ,R855-855.5 - Abstract
The recent success of autologous T cell-based therapies in hematological malignancies has spurred interest in applying similar immunotherapy strategies to the treatment of solid tumors. Identified nearly 4 decades ago, natural killer (NK) cells represent an arguably better cell type for immunotherapy development. Natural killer cells are cytotoxic lymphocytes that mediate the direct killing of transformed cells with reduced or absent major histocompatibility complex (MHC) and are the effector cells in antibody-dependent cell-mediated cytotoxicity. Unlike T cells, they do not require human leukocyte antigen (HLA) matching allowing for the adoptive transfer of allogeneic NK cells in the clinic. The development of NK cell-based therapies for solid tumors is complicated by the presence of an immunosuppressive tumor microenvironment that can potentially disarm NK cells rendering them inactive. The molecular imaging of NK cells in vivo will be crucial for the development of new therapies allowing for the immediate assessment of therapeutic response and off-target effects. A number of groups have investigated methods for detecting NK cells by optical, nuclear, and magnetic resonance imaging. In this review, we will provide an overview of the advances made in imaging NK cells in both preclinical and clinical studies.
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- 2018
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12. Comparison of thermoelectric properties of nanostructured Mg2Si, FeSi2, SiGe, and nanocomposites of SiGe–Mg2Si, SiGe–FeSi2
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Amin Nozariasbmarz, Palash Roy, Zahra Zamanipour, J. Houston Dycus, Matthew J. Cabral, James M. LeBeau, Jerzy S. Krasinski, and Daryoosh Vashaee
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Biotechnology ,TP248.13-248.65 ,Physics ,QC1-999 - Abstract
Thermoelectric properties of nanostructured FeSi2, Mg2Si, and SiGe are compared with their nanocomposites of SiGe–Mg2Si and SiGe–FeSi2. It was found that the addition of silicide nanoinclusions to SiGe alloy maintained or increased the power factor while further reduced the thermal conductivity compared to the nanostructured single-phase SiGe alloy. This resulted in ZT enhancement of Si0.88Ge0.12–FeSi2 by ∼30% over the broad temperature range of 500-950 °C compared to the conventional Si0.80Ge0.20 alloy. The Si0.88Ge0.12–Mg2Si nanocomposite showed constantly increasing ZT versus temperature up to 950 °C (highest measured temperature) reaching ZT ∼ 1.3. These results confirm the concept of silicide nanoparticle-in-SiGe-alloy proposed earlier by Mingo et al. [Nano Lett. 9, 711–715 (2009)].
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- 2016
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13. Le « polder » d'Erstein : objectifs, aménagements et retour d'expérience sur cinq ans de fonctionnement et de suivi scientifique environnemental (Rhin, France)
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L. SCHMITT, M. LEBEAU, M. TRÉMOLIÈRES, S. DEFRAEYE, C. COLI, E. DENNY, M. DILLINGER, T. BECK, J.C. DOR, P. GOMBERT, A. GUEIDAN, S. MANNE, J.P. PARTY, P. PERROTEY, M. PIQUETTE, U. ROECK, A. SCHNITZLER, O. SONNET, J.P. VACHER, V. VAUCLIN, M. WEISS, J.N. ZACHER, and P. WILMS
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Environmental technology. Sanitary engineering ,TD1-1066 ,Environmental sciences ,GE1-350 - Abstract
Après une brève présentation du Rhin supérieur et de ses aménagements, cet article présente les caractéristiques techniques et les modalités du fonctionnement du polder d'Erstein, un bassin de rétention de la rive française. Il dresse ensuite un bilan technique et synthétise de premiers résultats du suivi scientifique interdisciplinaire après cinq ans de fonctionnement du polder. Les améliorations écologiques observées concernent essentiellement l'hydrologie, l'hydrogéologie et la physicochimie, et (encore) assez peu la biologie. Sur cette base, de premières propositions pour la gestion future ont pu être formulées.
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- 2008
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