128 research outputs found
Orbital Dependent Phase Control in Ca2-xSrxRuO4
We present first-principles studies on the orbital states of the layered
perovskites CaSrRuO. The crossover from antiferromagnetic (AF)
Mott insulator for to nearly ferromagnetic (FM) metal at is
characterized by the systematic change of the orbital occupation. For the
AF side (), we present firm evidence for the ferro-orbital
ordering. It is found that the degeneracy of (or ) states is
lifted robustly due to the two-dimensional (2D) crystal-structure, even without
the Jahn-Teller distortion of RuO. This effect dominates, and the
cooperative occupation of orbital is concluded. In contrast to recent
proposals, the resulting electronic structure explains well both the observed
X-ray absorption spectra and the double peak structure of optical conductivity.
For the FM side (), however, the orbital with half filling opens a
pseudo-gap in the FM state and contributes to the spin =1/2 moment (rather
than =1 for =0.0 case) dominantly, while states are itinerant
with very small spin polarization, explaining the recent neutron data
consistently.Comment: 17 pages, 5 figure
5PMICROTUBULE-DEPOLYMERIZING AGENTS USED IN ANTIBODY-DRUG-CONJUGATES INDUCE ANTITUMOR ACTIVITY BY STIMULATION OF DENDRITIC CELLS
Antibody drug conjugates (ADCs) are emerging as powerful treatment strategies with outstanding target specificity and high therapeutic activity in cancer patients. While >30 ADCs are currently being investigated in clinical trials, brentuximabvedotin and T-DM1 represent clinically approved ADCs in cancer patients. We hypothesized that their sustained clinical responses could be related to the stimulation of an antitumor immune response. Indeed, the two microtubule-destabilizing agents Dolastatin 10 and Ansamitocin P3, from which the cytotoxic components of brentuximabvedotin and T-DM1 are derived, may serve as prototypes for a class of agents that induce tumor cell death and convert tumor resident, tolerogenic dendritic cells (DCs) into efficient antigen presenting cells (APCs). The two drugs induced phenotypic and functional maturation of murine splenic as well as human monocyte-derived DCs. In contrast, microtubule-stabilizing agents such as taxanes did not display this feature. In tumor models, both Dolastatin 10 and Ansamitocin P3 efficiently promoted antigen uptake and migration of tumor-resident DCs to tumor-draining lymph nodes, thereby potentiating tumor-specific T cell responses. Underlining the requirement of an intact host immune system for the full therapeutic benefit of these two compounds, their antitumor effect was far less pronounced in mice lacking adaptive immunity or dendritic cells. Combinations with immune checkpoint inhibition (anti-CTLA-4/-PD-1) did further augment antitumor immunity and tumor rejection, which was reflected by reduced Treg numbers and elevated effector function of tumor resident T cells. Ultimately, we were able to demonstrate peripheral immune cell activation and brisk T cell infiltration into tumors in patients previously treated with BrentuximabVedotin. Experiments are currently ongoing to investigate the immunological mode of action of T-DM1 using orthotopic breast cancer models and patients undergoing treatment. Our data reveal a novel mode of action for microtubule-depolymerizing agents and provide a strong rationale for clinical treatment regimens combining these with immune-based therapies. Disclosure: All authors have declared no conflicts of interes
The Earth System Prediction Suite: Toward a Coordinated U.S. Modeling Capability
The Earth System Prediction Suite (ESPS) is a collection of flagship U.S. weather and climate models and model components that are being instrumented to conform to interoperability conventions, documented to follow metadata standards, and made available either under open source terms or to credentialed users.The ESPS represents a culmination of efforts to create a common Earth system model architecture, and the advent of increasingly coordinated model development activities in the U.S. ESPS component interfaces are based on the Earth System Modeling Framework (ESMF), community-developed software for building and coupling models, and the National Unified Operational Prediction Capability (NUOPC) Layer, a set of ESMF-based component templates and interoperability conventions. This shared infrastructure simplifies the process of model coupling by guaranteeing that components conform to a set of technical and semantic behaviors. The ESPS encourages distributed, multi-agency development of coupled modeling systems, controlled experimentation and testing, and exploration of novel model configurations, such as those motivated by research involving managed and interactive ensembles. ESPS codes include the Navy Global Environmental Model (NavGEM), HYbrid Coordinate Ocean Model (HYCOM), and Coupled Ocean Atmosphere Mesoscale Prediction System (COAMPS); the NOAA Environmental Modeling System (NEMS) and the Modular Ocean Model (MOM); the Community Earth System Model (CESM); and the NASA ModelE climate model and GEOS-5 atmospheric general circulation model
Differential impact of two doses of antithymocyte globulin conditioning on lymphocyte recovery upon haploidentical hematopoietic stem cell transplantation
First-principles quantum transport modeling of spin-transfer and spin-orbit torques in magnetic multilayers
We review a unified approach for computing: (i) spin-transfer torque in
magnetic trilayers like spin-valves and magnetic tunnel junction, where
injected charge current flows perpendicularly to interfaces; and (ii)
spin-orbit torque in magnetic bilayers of the type
ferromagnet/spin-orbit-coupled-material, where injected charge current flows
parallel to the interface. Our approach requires to construct the torque
operator for a given Hamiltonian of the device and the steady-state
nonequilibrium density matrix, where the latter is expressed in terms of the
nonequilibrium Green's functions and split into three contributions. Tracing
these contributions with the torque operator automatically yields field-like
and damping-like components of spin-transfer torque or spin-orbit torque
vector, which is particularly advantageous for spin-orbit torque where the
direction of these components depends on the unknown-in-advance orientation of
the current-driven nonequilibrium spin density in the presence of spin-orbit
coupling. We provide illustrative examples by computing spin-transfer torque in
a one-dimensional toy model of a magnetic tunnel junction and realistic
Co/Cu/Co spin-valve, both of which are described by first-principles
Hamiltonians obtained from noncollinear density functional theory calculations;
as well as spin-orbit torque in a ferromagnetic layer described by a
tight-binding Hamiltonian which includes spin-orbit proximity effect within
ferromagnetic monolayers assumed to be generated by the adjacent monolayer
transition metal dichalcogenide.Comment: 22 pages, 9 figures, PDFLaTeX; prepared for Springer Handbook of
Materials Modeling, Volume 2 Applications: Current and Emerging Material
Untersuchungen zur Molekularpathologie des Hodgkin-Lymphoms - Klonierung des I kappa B epsilon Gens und Mutationsanalyse in Einzelzellen
Role of stem cell transplantation in treatment of primary cutaneous T-cell lymphoma
Background. Within the heterogeneous group of cutaneous T-cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. Objective. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. Material and methods. A literature search using the keywords hematopoietic stem cell transplantation and cutaneous T-cell lymphoma was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. Results. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Conclusion. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T-cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision
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