•We present a novel assessment methodology for electric vehicles in mid-haul logistics.•We develop a matheuristic to solve large-scale instances.•We present a real-world case study to showcase the ...competitiveness of electric vehicles.•We provide extensive sensitivity studies and managerial insights on the competitiveness of electric vehicles.
Electric commercial vehicles can contribute significantly to sustainable transportation. However, they are still perceived as being less economically viable than internal combustion engine vehicles. To this end, we analyze the deployment of electric commercial vehicles in retail mid-haul logistics fleets for current and future technology scenarios. We develop a novel assessment methodology that combines total cost of ownership calculations with a rich location-routing model. We consider integrated strategic network design and operational routing decisions over a multi-period time horizon, accounting for mixed fleets of electric and conventional vehicles and battery degradation. To solve this problem, we develop a novel matheuristic that embeds a state-of-the-art metaheuristic to take operational routing decisions. With this framework, we analyze a possible transition towards electrified logistics fleets. Starting with a real-world case, we perform sensitivity analyses based on a technology roadmap and further network structures. We discuss cost structures, the time-dependent nature of investment decisions, operational characteristics, and potential emissions savings. We show that in certain cases an electrification of mid-haul logistics fleets is operationally feasible, economically viable, and provides environmental advantages.
We present a three-dimensional nonlinear finite element formulation for dielectric elastomers. The mechanical and electrical governing equations are solved monolithically using an implicit time ...integrator, where the governing finite element equations are given for both static and dynamic cases. By accounting for inertial terms in conjunction with the Arruda–Boyce rubber hyperelastic constitutive model, we demonstrate the ability to capture the various modes of inhomogeneous deformation, including pull-in instability and wrinkling, that may result in dielectric elastomers that are subject to various forms of electrostatic loading. The formulation presented here forms the basis for needed computational tools that can elucidate the electromechanical behavior and properties of dielectric elastomers that are used for engineering applications.
Video observation (VO) is an established tool for observing toothbrushing behaviour, however, it is a subjective method requiring thorough calibration and training, and the toothbrush position is not ...always clearly visible. As automated tracking of motions may overcome these disadvantages, the study aimed to compare observational data of habitual toothbrushing as well as of post-instruction toothbrushing obtained from motion tracking (MT) to observational data obtained from VO. One-hundred-three subjects (37.4±14.7 years) were included and brushed their teeth with a manual (MB; n = 51) or a powered toothbrush (PB; n = 52) while being simultaneously video-filmed and tracked. Forty-six subjects were then instructed how to brush their teeth systematically and were filmed/tracked for a second time. Videos were analysed with INTERACT (Mangold, Germany); parameters of interest were toothbrush position, brushing time, changes between areas (events) and the Toothbrushing Systematic Index (TSI). Overall, the median proportion (min; max) of identically classified toothbrush positions (both sextant/surface correct) in a brushing session was 87.8% (50.0; 96.9), which was slightly higher for MB compared to PB (90.3 (50.0; 96.9) vs 86.5 (63.7; 96.5) resp.; p = 0.005). The number of events obtained from MT was higher than from VO (p < 0.001) with a moderate to high correlation between them (MB: ρ = 0.52, p < 0.001; PB: ρ = 0.87; p < 0.001). After instruction, both methods revealed a significant increase of the TSI regardless of the toothbrush type (p < 0.001 each). Motion tracking is a suitable tool for observing toothbrushing behaviour, is able to measure improvements after instruction, and can be used with both manual and powered toothbrushes.
We utilize the recently developed surface Cauchy–Born model, which extends the standard Cauchy–Born theory to account for surface stresses due to undercoordinated surface atoms, to study the coupled ...influence of boundary conditions and surface stresses on the resonant properties of
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gold nanowires with
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surfaces. There are two major purposes to the present work. First, we quantify, for the first time, variations in the nanowire resonant frequencies due to surface stresses as compared to the corresponding bulk material which does not observe surface effects within a finite deformation framework depending on whether fixed/free or fixed/fixed boundary conditions are utilized. We find that while the resonant frequencies of fixed/fixed nanowires are elevated as compared to the corresponding bulk material, the resonant frequencies of fixed/free nanowires are reduced as a result of compressive strain caused by the surface stresses. Furthermore, we find that for a diverse range of nanowire geometries, the variation in resonant frequencies for both boundary conditions due to surface stresses is a geometric effect that is characterized by the nanowire aspect ratio. The present results are found to agree well with existing experimental data for both types of boundary conditions.
The second major goal of this work is to quantify, for the first time, how both the residual (strain-independent) and surface elastic (strain-dependent) parts of the surface stress impact the resonant frequencies of metal nanowires within the framework of nonlinear, finite deformation kinematics. We find that if finite deformation kinematics are considered, the strain-independent surface stress substantially alters the resonant frequencies of the nanowires; however, we also find that the strain-dependent surface stress has a significant effect, one that can be comparable to or even larger than the effect of the strain-independent surface stress depending on the boundary condition, in shifting the resonant frequencies of the nanowires as compared to the bulk material.
•New finite element formulation for dielectric elastomers.•Q1P0 model alleviates locking.•Creasing to cratering instability captured, with experimental comparison.
We present a dynamic finite element ...formulation for dielectric elastomers that significantly alleviates the problem of volumetric locking that occurs due to the incompressible nature of the elastomers. We accomplish this by modifying the Q1P0 formulation of Simo et al. 1, and adapting it to the electromechanical coupling that occurs in dielectric elastomers. We demonstrate that volumetric locking has a significant impact on the critical electric fields that are necessary to induce electromechanical instabilities such as creasing and cratering in dielectric elastomers, and that the locking effects are most severe in problems related to recent experiments that involve significant constraints upon the deformation of the elastomers. We then compare the results using the new Q1P0 formulation to that obtained using standard 8-node linear and 27-node quadratic hexahedral elements to demonstrate the capability of the proposed approach. Finally, direct comparison to the recent experimental work on the creasing instability on dielectric polymer surface by Wang et al. 2 is presented. The present formulation demonstrates good agreement to experiment for not only the critical electric field for the onset of the creasing instability, but also the experimentally observed average spacing between the creases.
Ladder‐type pentaphenyl chromophores have a rigid, planar π‐system and show bright fluorescence featuring pronounced vibrational structure. Such moieties are ideal for studying interchromophoric ...interactions and delocalization of electronic excitations. We report the synthesis of helical polymers with a rigid square structure based on spiro‐linked ladder‐type pentaphenyl units. The variation of circular dichroism with increasing chain length provides direct evidence for delocalization of electronic excitations over at least 10 monomeric units. The change in the degree of circular polarization of the fluorescence across the vibronic side bands shows that vibrational motion can localize the excitation dynamically to almost one single unit through breakdown of the Born‐Oppenheimer approximation. The dynamic conversion between delocalized and localized excited states provides a new paradigm for interpreting circular dichroism in helical polymers such as proteins and polynucleic acids.
Rectangular π‐conjugated ladder polymers of one particular handedness provide a square answer to the question of delocalization of their lowest‐energy photoexcitation: the coupling to vibrations makes the excitation shaky. Exciton localization is a dynamic process and the excitation “breathes” in concert with the zero‐point vibrational motion.
EC145 (vintafolide), a conjugate of folic acid and the vinca alkaloid desacetylvinblastine hydrazide (DAVLBH), is a ligand for the folate receptor (FR), with activity against FR-positive tumor ...xenografts in vivo. This phase I study determined the maximum-tolerated dose (MTD) of EC145 administered as a bolus intravenous injection or 1-hour infusion in patients with refractory solid tumors.
EC145 was administered as a bolus injection or 1-hour infusion on days 1, 3, and 5 and days 15, 17, and 19 of each 28-day cycle with dose escalation in cohorts of three to six patients until the MTD was identified. Plasma pharmacokinetics were determined on days 1 and 3 of the first cycle.
The MTD of EC145 was 2.5 mg when administered as either a bolus injection or 1-hour infusion. Constipation was the dose-limiting toxicity with both routes. Constipation, nausea, fatigue, and vomiting were the most commonly reported adverse events. One partial response to therapy was observed in a patient with metastatic ovarian cancer.
EC145 administered by bolus injection or as a 1-hour infusion at a dose of 2.5 mg on days 1, 3, and 5 and days 15, 17, and 19 of a 28-day cycle has an acceptable safety profile in patients with advanced cancer. On the basis of these findings, phase II studies of EC145 have been initiated in patients with advanced epithelial ovarian cancer and non-small-cell lung cancer.
A surface Cauchy-Born model for nanoscale materials Park, Harold S.; Klein, Patrick A.; Wagner, Gregory J.
International journal for numerical methods in engineering,
3 December 2006, Letnik:
68, Številka:
10
Journal Article
Chimeric antigen receptor (CAR)-T cell therapy has transformed pediatric oncology by producing high remission rates and potent effects in CD19+ B-cell malignancies. This scenario is ideal as CD19 ...expression is homogeneous and human blood provides a favorable environment for CAR-T cells to thrive and destroy cancer cells (along with normal B cells). Yet, CAR-T cell therapies for solid tumors remain challenged by fewer tumor targets and poor CAR-T cell performances in a hostile tumor microenvironment. For acute myeloid leukemia and childhood solid tumors such as osteosarcoma, the primary treatment is systemic chemotherapy that often falls short of expectation especially for relapsed and refractory conditions. We aim to develop a CAR-T adaptor molecule (CAM)-based therapy that uses a bispecific small-molecule ligand EC17, fluorescein isothiocyanate (FITC) conjugated with folic acid, to redirect FITC-specific CAR-T cells against folate receptor (FR)-positive tumors. As previously confirmed in rodents as well as in human clinical studies, EC17 penetrates solid tumors within minutes and is retained due to high affinity for the FR, whereas unbound EC17 rapidly clears from the blood and from receptor-negative tissues. When combined with a rationally designed CAR construct, EC17 CAM was shown to trigger CAR-modified T cell activation and cytolytic activity with a low FR threshold against tumor targets. However, maximal cytolytic potential correlated with (i) functional FR levels (in a semi-log fashion), (ii) the amount of effector cells present, and (iii) tumors' natural sensitivity to T cell mediated killing. In tumor-bearing mice, administration of EC17 CAM was the key to drive CAR-T cell activation, proliferation, and persistence against FR+ pediatric hematologic and solid tumors. In our modeling systems, cytokine release syndrome (CRS) was induced under specific conditions, but the risk of severe CRS could be easily mitigated or prevented by applying intermittent dosing and/or dose-titration strategies for the EC17 CAM. Our approach offers the flexibility of antigen control, prevents T cell exhaustion, and provides additional safety mechanisms including rapid reversal of severe CRS with intravenous sodium fluorescein. In this paper, we summarize the translational aspects of our technology in support of clinical development.
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