Adaptation of Oxidative Phosphorylation Machinery Compensates for Hepatic Lipotoxicity in Early Stages of MAFLD

Alterations in mitochondrial function are an important control variable in the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), while also noted by increased de novo lipogenesis (DNL) and hepatic insulin resistance. We hypothesized that the organization and function of a mitochondrial electron transport chain (ETC) in this pathologic condition is a consequence of shifted substrate availability. We addressed this question using a transgenic mouse model with increased hepatic insulin resistance and DNL due to constitutively active human SREBP-1c. The abundance of ETC complex subunits and components of key metabolic pathways are regulated in the liver of these animals. Further omics approaches combined with functional assays in isolated liver mitochondria and primary hepatocytes revealed that the SREBP-1c-forced fatty liver induced a substrate limitation for oxidative phosphorylation, inducing enhanced complex II activity. The observed increased expression of mitochondrial genes may have indicated a counteraction. In conclusion, a shift of available substrates directed toward activated DNL results in increased electron flows, mainly through complex II, to compensate for the increased energy demand of the cell. The reorganization of key compounds in energy metabolism observed in the SREBP-1c animal model might explain the initial increase in mitochondrial function observed in the early stages of human MAFLD.     

SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73⁺ and CK14⁺ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.     

AFFECT IN TUTORING DIALOGUES

ABSTRACT

This paper is about INES, an intelligent, multimodal tutoring environment, and how we build a tutor agent in the environment that tries to be sensitive to the mental state of the student that interacts with it. The environment was primarily designed to help students practice nursing tasks. For example, one of the implemented tasks is to give a virtual patient a subcutaneous injection. The students can interact multimodally using speech and a haptic device under the guidance of the virtual embodied tutor. INES takes into account elements of the student's character and an appraisal of the student's actions to estimate the mental state of the student. This information is used to plan and execute the actions and responses of the tutor agent.     

Weak signal identification with semantic web mining

We investigate an automated identification of weak signals according to Ansoff to improve strategic planning and technological forecasting. Literature shows that weak signals can be found in the organization’s environment and that they appear in different contexts. We use internet information to represent organization’s environment and we select these websites that are related to a given hypothesis. In contrast to related research, a methodology is provided that uses latent semantic indexing (LSI) for the identification of weak signals. This improves existing knowledge based approaches because LSI considers the aspects of meaning and thus, it is able to identify similar textual patterns in different contexts. A new weak signal maximization approach is introduced that replaces the commonly used prediction modeling approach in LSI. It enables to calculate the largest number of relevant weak signals represented by singular value decomposition (SVD) dimensions. A case study identifies and analyses weak signals to predict trends in the field of on-site medical oxygen production. This supports the planning of research and development (R&D) for a medical oxygen supplier. As a result, it is shown that the proposed methodology enables organizations to identify weak signals from the internet for a given hypothesis. This helps strategic planners to react ahead of time.     

The acceptance of Tablet-PCs in classroom instruction: The teachers’ perspectives

Limited research has been conducted on the integration of Tablet-PCs in classroom instruction. This paper reports a qualitative study which investigates the acceptance of Tablet-PCs, seen as technological innovation, amongst teachers. The research approach intends to complement research on the acceptance of technology through a more detailed qualitative examination. Semi-structured interviews were conducted with 18 teachers during a pilot project introducing Tablet-PCs to classroom instruction at three different schools. The findings indicate diversity in the attitude of teachers towards the technology, but also with regards to the performance expectancy and the facilitating conditions.     

Third–Generation Pleated Pneumatic Artificial Muscles for Robotic Applications: Development and Comparison with McKibben Muscle

This paper introduces the third generation of Pleated Pneumatic Artificial Muscles (PPAM), which has been developed to simplify the production over the first and second prototype. This type of artificial muscle was developed to overcome dry friction and material deformation, which is present in the widely used McKibben muscle. The essence of the PPAM is its pleated membrane structure which enables the muscle to work at low pressures and at large contractions. In order to validate the new PPAM generation, it has been compared with the mathematical model and the previous generation. The new production process and the use of new materials introduce improvements such as 55% reduction in the actuator’s weight, a higher reliability, a 75% reduction in the production time and PPAMs can now be produced in all sizes from 4 to 50?cm. This opens the possibility to commercialize this type of muscles so others can implement it. Furthermore, a comparison with experiments between PPAM and Festo McKibben muscles is discussed. Small PPAMs present similar force ranges and larger contractions than commercially available McKibben-like muscles. The use of series arrangements of PPAMs allows for large strokes and relatively small diameters at the same time and, since PPAM 3.0 is much more lightweight than the commong McKibben models made by Festo, it presents better force-to-mass and energy to mass ratios than Festo models.     

Identification of quasi-optimal regions in the design space using surrogate modeling

The use of Surrogate Based Optimization (SBO) is widely spread in engineering design to find optimal performance characteristics of expensive simulations (forward analysis: from input to optimal output). However, often the practitioner knows a priori the desired performance and is interested in finding the associated input parameters (reverse analysis: from desired output to input). A popular method to solve such reverse (inverse) problems is to minimize the error between the simulated performance and the desired goal. However, there might be multiple quasi-optimal solutions to the problem. In this paper, the authors propose a novel method to efficiently solve inverse problems and to sample Quasi-Optimal Regions (QORs) in the input (design) space more densely. The development of this technique, based on the probability of improvement criterion and kriging models, is driven by a real-life problem from bio-mechanics, i.e., determining the elasticity of the (rabbit) tympanic membrane, a membrane that converts acoustic sound wave into vibrations of the middle ear ossicular bones.     

Optimized butterfly specimen for the fracture testing of sheet materials under combined normal and shear loading

The present paper is concerned with multi-axial ductile fracture experiments on sheet metals. Different stress-states are achieved within a flat specimen by applying different combinations of normal and transverse loads to the specimen boundaries. The specimen geometry is optimized such that fracture initiates remote from the free specimen boundaries. Fracture experiments are carried out on TRIP780 steel for four different loading conditions, varying from pure shear to transverse plane strain tension. Hybrid experimental–numerical analyses are performed to determine the stress and strain fields within the specimen gage section. The results show that strain localization cannot be avoided prior to the onset of fracture. Through-thickness necking prevails under tension-dominated loading while the deformation localizes along a band crossing the entire gage section under shear-dominated loading. Both experimental and simulation results demonstrate that the proposed fracture testing method is very sensitive to imperfections in the specimen machining. The loading paths to fracture are determined in terms of stress triaxiality, Lode angle parameter and equivalent plastic strain. The experimental data indicates that the relationship between the stress triaxiality and the equivalent plastic strain at the onset of ductile fracture is not unique.