VICAR-DIGITAL image processing system

Computer program corrects various photometic, geometric and frequency response distortions in pictures. The program converts pictures to a number of elements, with each elements optical density quantized to a numerical value. The translated picture is recorded on magnetic tape in digital form for subsequent processing and enhancement by computer

Explainable Artificial Intelligence for Mechanics: Physics-Explaining Neural Networks for Constitutive Models

(Artificial) neural networks have become increasingly popular in mechanics and materials sciences to accelerate computations with model order reduction techniques and as universal models for a wide variety of materials. However, the major disadvantage of neural networks remains: their numerous parameters are challenging to interpret and explain. Thus, neural networks are often labeled as black boxes, and their results often elude human interpretation. The new and active field of physics-informed neural networks attempts to mitigate this disadvantage by designing deep neural networks on the basis of mechanical knowledge. By using this a priori knowledge, deeper and more complex neural networks became feasible, since the mechanical assumptions can be explained. However, the internal reasoning and explanation of neural network parameters remain mysterious. Complementary to the physics-informed approach, we propose a first step towards a physics-explaining approach, which interprets neural networks trained on mechanical data a posteriori. This proof-of-concept explainable artificial intelligence approach aims at elucidating the black box of neural networks and their high-dimensional representations. Therein, the principal component analysis decorrelates the distributed representations in cell states of RNNs and allows the comparison to known and fundamental functions. The novel approach is supported by a systematic hyperparameter search strategy that identifies the best neural network architectures and training parameters. The findings of three case studies on fundamental constitutive models (hyperelasticity, elastoplasticity, and viscoelasticity) imply that the proposed strategy can help identify numerical and analytical closed-form solutions to characterize new materials

Renal Transporter-Mediated Drug-Biomarker Interactions of the Endogenous Substrates Creatinine and N1 -Methylnicotinamide : A PBPK Modeling Approach

Endogenous biomarkers for transporter-mediated drug-drug interaction (DDI) predictions represent a promising approach to facilitate and improve conventional DDI investigations in clinical studies. This approach requires high sensitivity and specificity of biomarkers for the targets of interest (e.g., transport proteins), as well as rigorous characterization of their kinetics, which can be accomplished utilizing physiologically-based pharmacokinetic (PBPK) modeling. Therefore, the objective of this study was to develop PBPK models of the endogenous organic cation transporter (OCT)2 and multidrug and toxin extrusion protein (MATE)1 substrates creatinine and N1-methylnicotinamide (NMN). Additionally, this study aimed to predict kinetic changes of the biomarkers during administration of the OCT2 and MATE1 perpetrator drugs trimethoprim, pyrimethamine, and cimetidine. Whole-body PBPK models of creatinine and NMN were developed utilizing studies investigating creatinine or NMN exogenous administration and endogenous synthesis. The newly developed models accurately describe and predict observed plasma concentration-time profiles and urinary excretion of both biomarkers. Subsequently, models were coupled to the previously built and evaluated perpetrator models of trimethoprim, pyrimethamine, and cimetidine for interaction predictions. Increased creatinine plasma concentrations and decreased urinary excretion during the drug-biomarker interactions with trimethoprim, pyrimethamine, and cimetidine were well-described. An additional inhibition of NMN synthesis by trimethoprim and pyrimethamine was hypothesized, improving NMN plasma and urine interaction predictions. To summarize, whole-body PBPK models of creatinine and NMN were built and evaluated to better assess creatinine and NMN kinetics while uncovering knowledge gaps for future research. The models can support investigations of renal transporter-mediated DDIs during drug development

Morphological stability of rod-shaped continuous phases

Morphological transition of a rod-shaped phase into a string of spherical particles is commonly observed in the microstructures of alloys during solidification (Ratke and Mueller, 2006). This transition phenomenon can be explained by the classic Plateau-Rayleigh theory which was derived for fluid jets based on the surface area minimization principle. The quintessential work of Plateau-Rayleigh considers tiny perturbations (amplitude much less than the radius) to the continuous phase and for large amplitude perturbations, the breakup condition for the rod-shaped phase is still a knotty issue. Here, we present a concise thermodynamic model based on the surface area minimization principle as well as a non-linear stability analysis to generalize Plateau-Rayleigh’s criterion for finite amplitude perturbations. Our results demonstrate a breakup transition from a continuous phase via dispersed particles towards a uniform-radius cylinder, which has not been found previously, but is observed in our phase-field simulations. This new observation is attributed to a geometric constraint, which was overlooked in former studies. We anticipate that our results can provide further insights on microstructures with spherical particles and cylinder-shaped phases