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Electromagnetics of superconductor/paramagnet heterostructures
No full textRedistribution of the transport current in a superconductor affected by paramagnetic shields provides a possibility of strongly overcritical states and a drastic reduction of AC losses in thin superconductor films and tubes. Such superconductors subject to para- or diamagnetic shielding are studied by means of the potential theory and the critical state model when carrying a transport current or exposed to an external magnetic field. Analytical results are obtained for a number of shielding geometries and confirmed by numerical solutions. It is shown that using magnetostatic-electrostatic analogies allows consideration of paramagnetic shielding configurations of arbitrary shapes and magnetic permeabilities by means of common finite-element solvers to enhance the dissipation-free transport currents in superconductors and reduce AC losses in them. Furthermore, using the generalized London theory, the penetration of magnetic flux into magnetically shielded bulk superconductors is studied and the enhancement of the Bean-Livingston barrier is established
Conditional activation of an anti-IgM antibody-drug conjugate for precise B cell lymphoma targeting
No full textCancerous B cells are almost indistinguishable from their non-malignant counterparts regarding their surface antigen expression. Accordingly, the challenge to be faced consists in elimination of the malignant B cell population while maintaining a functional adaptive immune system. Here, we present an IgM-specific antibody-drug conjugate masked by fusion of the epitope-bearing IgM constant domain. Antibody masking impaired interaction with soluble pentameric as well as cell surface-expressed IgM molecules rendering the antibody cytotoxically inactive. Binding capacity of the anti-IgM antibody drug conjugate was restored upon conditional protease-mediated demasking which consequently enabled target-dependent antibody internalization and subsequent induction of apoptosis in malignant B cells. This easily adaptable approach potentially provides a novel mechanism of clonal B cell lymphoma eradication to the arsenal available for non-Hodgkin's lymphoma treatment
Sample coverage affects diversity measures of bird communities along a natural recovery gradient of abandoned agriculture in tropical lowland forests
No full textLos bosques tropicales antiguos siguen disminuyendo en todo el mundo, lo que provoca una enorme pérdida de biodiversidad. La capacidad de la expansión de los bosques de segundo crecimiento para contrarrestar la pérdida de biodiversidad depende del contexto y es controvertida. Para comprobar la recuperación de las comunidades de aves a lo largo de un gradiente que abarca pastos activos, plantaciones de cacao, bosques en regeneración en tierras utilizadas por última vez para la agricultura entre 1 y 38 años atrás, y bosques primarios, realizamos grabaciones de audio simultáneas en 66 parcelas. A partir de dichas grabaciones, un experto identificó todas las especies de aves detectadas en momentos estandarizados a lo largo del día. El área de estudio se caracteriza por la típica agricultura a pequeña escala con árboles remanentes en el bosque del Chocó ecuatoriano. Para cuantificar diferentes aspectos de la biodiversidad, utilizamos números de Hill basados en la incidencia, centrándonos en especies poco frecuentes, frecuentes y altamente frecuentes en diversidad taxonómica, funcional y filogenética, teniendo en cuenta la cobertura de la muestra (una medida objetiva de la completitud de la muestra). La composición de la comunidad de aves siguió el gradiente de rebrote representado en el primer eje de la ordenación. Las diferencias en las comunidades de aves también fueron robustas a los cambios en la cobertura de la muestra. La cobertura de las muestras disminuyó significativamente a lo largo del gradiente de recuperación y afectó a las distintas medidas de diversidad alfa. Aunque los resultados controlados por la cobertura muestral no mostraron cambios en la diversidad taxonómica y filogenética, la diversidad funcional de especies poco frecuentes, frecuentes y muy frecuentes disminuyó a lo largo del gradiente de recuperación. Las plantaciones de cacao mostraron valores de diversidad particularmente elevados, lo que pone de relieve el potencial de estos parches para sustentar especies forestales y arbustivas en la agricultura. Además, varias especies forestales utilizaron regularmente las áreas agrícolas, inducidas por árboles remanentes característicos del paisaje agrícola a pequeña escala de nuestra región de estudio. Síntesis y aplicaciones . Nuestros resultados ponen de manifiesto la importancia de estandarizar las medidas de biodiversidad e incorporar la diversidad beta en el seguimiento de la biodiversidad. Hemos demostrado que la diversidad taxonómica, filogenética y funcional de las aves puede ser alta en bosques secundarios dentro de paisajes agrícolas de pequeña escala. Esto pone de manifiesto el potencial de recuperación de los bosques naturales, en particular cuando las parcelas de recuperación están integradas en una matriz forestal que incluye bosques antiguos
Use of 5-Thio-L-Fucose to modulate binding affinity of therapeutic proteins
No full textThe reduction of antibody core-fucosylation is known to enhance antibody-dependent cellular cytotoxicity (ADCC). In this study, 5-Thio-l-Fucose (ThioFuc) was investigated as a media and feed supplement for modulating the fucosylation profile of therapeutic proteins and, thereby, improving the resulting effector functions. Glycan analysis of five different therapeutic proteins produced by a diverse set of Chinese hamster ovary cell lines demonstrated a clone dependent impact of ThioFuc treatment. Using rituximab as a model, an efficient dose- and time-dependent reduction of core-fucosylation up to a minimum of 5% were obtained by ThioFuc. Besides a concomitant increase in the afucosylation level up to 48%, data also revealed up to 47% incorporation of ThioFuc in place of core-fucosylation. In accordance with the glycan data, antibodies produced in the presence of ThioFuc revealed an enhanced FcγRIIIa binding up to 7.7-fold. Furthermore, modified antibodies subjected to a cell-based ADCC reporter bioassay proved to exert both a 1.5-fold enhanced ADCC efficacy and 2.6-fold enhancement in potency in comparison to their native counterparts—both of which contribute to an improvement in the ADCC activity. In conclusion, ThioFuc is a potent fucose derivative with potential applications in drug development processes
The effect of propagation saw test geometries on critical cut length
No full textFor a slab avalanche to release, a crack in a weak snow layer beneath a cohesive snow slab has to initiate and propagate. Information on crack propagation is essential for assessing avalanche triggering potential. In the field, this information can be gathered with the propagation saw test (PST), a field test that provides valuable data on crack propagation propensity. The first PSTs were performed about 20 years ago and standards have since been established. However, there are still differences in how the PST is performed. Standards in North America require the column ends to be cut vertically, whereas in Europe they are typically cut normal to the slope. In this study, we investigate the effect of these different column geometries on the critical cut length. To this end, we conducted 27 pairs of PST experiments, each pair consisting of one PST with slope-normal cut ends and one PST with vertical-cut ends. Our experiments showed that PSTs with normal cut ends have up to 50 % shorter critical cut lengths, and the difference predominantly depends on the slope angle and slab thickness. We developed two load-based models to convert critical cut lengths between the test geometries: (i) a uniform slab model that treats the slab as one uniform layer and (ii) a layered model that accounts for stratification. For validation, we compare these models with a modern fracture mechanical model. For the rather uniform slabs of our experiments, both load-based models were in excellent agreement with measured data. For slabs with an artificial layering, the uniform load–model predictions reveal deviations from the fracture mechanical model, whereas the layered model was still in excellent agreement. This study reveals the influence that the geometry of field tests and the slope angle of the field site have on test results. It also shows that only accurately prepared field tests can be reliable and therefore meaningful. However, we provide models to correct for imprecise field test geometry effects on the critical cut length
The effect of propagation saw test geometries on critical cut length
No full textFor a slab avalanche to release, a crack in a weak snow layer beneath a cohesive snow slab has to initiate and propagate. Information on crack propagation is essential for assessing avalanche triggering potential. In the field, this information can be gathered with the propagation saw test (PST), a field test that provides valuable data on crack propagation propensity. The first PSTs were performed about 20 years ago and standards have since been established. However, there are still differences in how the PST is performed. Standards in North America require the column ends to be cut vertically, whereas in Europe they are typically cut normal to the slope. In this study, we investigate the effect of these different column geometries on the critical cut length. To this end, we conducted 27 pairs of PST experiments, each pair consisting of one PST with slope-normal cut ends and one PST with vertical-cut ends. Our experiments showed that PSTs with normal cut ends have up to 50 % shorter critical cut lengths, and the difference predominantly depends on the slope angle and slab thickness. We developed two load-based models to convert critical cut lengths between the test geometries: (i) a uniform slab model that treats the slab as one uniform layer and (ii) a layered model that accounts for stratification. For validation, we compare these models with a modern fracture mechanical model. For the rather uniform slabs of our experiments, both load-based models were in excellent agreement with measured data. For slabs with an artificial layering, the uniform load–model predictions reveal deviations from the fracture mechanical model, whereas the layered model was still in excellent agreement. This study reveals the influence that the geometry of field tests and the slope angle of the field site have on test results. It also shows that only accurately prepared field tests can be reliable and therefore meaningful. However, we provide models to correct for imprecise field test geometry effects on the critical cut length
Enhanced Hemodynamics of Anisometric TPMS Topology Reduce Blood Clotting in 3D Printed Blood Contactors
No full textArtificial organs, such as extracorporeal membrane oxygenators, dialyzers, and hemoadsorber cartridges, face persistent challenges related to the flow distribution within the cartridge. This uneven flow distribution leads to clot formation and inefficient mass transfer over the device's functional surface. In this work, a comprehensive methodology is presented for precisely integrating triply periodic minimal surfaces (TPMS) into module housings and question whether the internal surface topology determining the flow distribution affects blood coagulation. Three module types are compared with different internal topologies: tubular, isometric, and anisometric TPMS. First, this study includes a computational fluid dynamics (CFD) simulation of the internal hemodynamics, validated through experimental residence time distributions (RTD). Blood tests using human whole blood and subsequent visualization of blood clots by computed tomography, allow the quantification of structure‐induced blood clotting. The results indicate that TPMS topologies, particularly anisometric ones, serve as effective flow distributors and significantly reduce and delay blood clotting compared to conventional tubular geometries. For these novel TPMS modules, the inner surfaces can be activated chemically or functionalized to function as a selective adsorption site or biocatalytic surface or made of a permeable material to facilitate mass transfer
Enhanced hemodynamics of anisometric TPMS topology reduce blood clotting in 3D printed blood contactors
No full textArtificial organs, such as extracorporeal membrane oxygenators, dialyzers, and hemoadsorber cartridges, face persistent challenges related to the flow distribution within the cartridge. This uneven flow distribution leads to clot formation and inefficient mass transfer over the device's functional surface. In this work, a comprehensive methodology is presented for precisely integrating triply periodic minimal surfaces (TPMS) into module housings and question whether the internal surface topology determining the flow distribution affects blood coagulation. Three module types are compared with different internal topologies: tubular, isometric, and anisometric TPMS. First, this study includes a computational fluid dynamics (CFD) simulation of the internal hemodynamics, validated through experimental residence time distributions (RTD). Blood tests using human whole blood and subsequent visualization of blood clots by computed tomography, allow the quantification of structure‐induced blood clotting. The results indicate that TPMS topologies, particularly anisometric ones, serve as effective flow distributors and significantly reduce and delay blood clotting compared to conventional tubular geometries. For these novel TPMS modules, the inner surfaces can be activated chemically or functionalized to function as a selective adsorption site or biocatalytic surface or made of a permeable material to facilitate mass transfer
Rational Design of Vanadia-Based Propane ODH Catalysts: A Multiple Operando Spectroscopic Investigation of VOₓ/TiO₂/CeO₂
No full textThe understanding of reaction mechanisms of supported metal oxide catalysts has significantly increased over the last years due to new methods being applied. This increased knowledge allows to develop approaches towards catalytic materials for reactions with low selectivities by rational design, such as the oxidative dehydrogenation (ODH) of propane, which is of great technical importance. Vanadia (VOₓ) supported on reducible oxides (TiO₂, CeO₂, etc.) has shown promising catalytic properties in propane ODH. In this study, we followed a rational-design approach employing atomic layer deposition (ALD) to synthesize a VOₓ/TiOₓ/CeO₂ catalyst with superior selectivity, by combining favourable properties of the individual catalysts (VOₓ/TiO₂, VOₓ/CeO₂). By applying multiple spectroscopies, including multi-wavelength Raman, UV-Vis, DRIFT, and XP spectroscopy as well as XRD, we were able to identify the functions of each oxide and develop a mechanistic picture. The increased selectivity is the result of distinct interactions between the oxides that slow down the oxygen dynamics in the catalyst and favour reaction pathways beneficial to propylene formation. Our findings highlight the use of rational design to develop improved catalysts based on previously established mechanistic knowledge
