Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs

Disorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies.

Simple epidemic models with segmentation can be better than complex ones

Given a sequence of epidemic events, can a single epidemic model capture its dynamics during the entire period? How should we divide the sequence into segments to better capture the dynamics? Throughout human history, infectious diseases (e.g., the Black Death and COVID-19) have been serious threats. Consequently, understanding and forecasting the evolving patterns of epidemic events are critical for prevention and decision making. To this end, epidemic models based on ordinary differential equations (ODEs), which effectively describe dynamic systems in many fields, have been employed. However, a single epidemic model is not enough to capture long-term dynamics of epidemic events especially when the dynamics heavily depend on external factors (e.g., lockdown and the capability to perform tests). In this work, we demonstrate that properly dividing the event sequence regarding COVID-19 (specifically, the numbers of active cases, recoveries, and deaths) into multiple segments and fitting a simple epidemic model to each segment leads to a better fit with fewer parameters than fitting a complex model to the entire sequence. Moreover, we propose a methodology for balancing the number of segments and the complexity of epidemic models, based on the Minimum Description Length principle. Our methodology is (a) Automatic: not requiring any user-defined parameters, (b) Model-agnostic: applicable to any ODE-based epidemic models, and (c) Effective: effectively describing and forecasting the spread of COVID-19 in 70 countries.

APOE ɛ4 Allele Moderates the Association Between Basal Forebrain Nuclei Volumes and Allocentric Navigation in Older Adults Without Dementia

Background: Cholinergic deficit and medial temporal lobe (MTL) atrophy are hallmarks of Alzheimer’s disease (AD) leading to early allocentric spatial navigation (aSN) impairment. APOE ɛ4 allele (E4) is a major genetic risk factor for late-onset AD and contributes to cholinergic dysfunction. Basal forebrain (BF) nuclei, the major source of acetylcholine, project into multiple brain regions and, along with MTL and prefrontal cortex (PFC), are involved in aSN processing. Objective: We aimed to determine different contributions of individual BF nuclei atrophy to aSN in E4 positive and E4 negative older adults without dementia and assess whether they operate on aSN through MTL and PFC or independently from these structures. Methods: 120 participants (60 E4 positive, 60 E4 negative) from the Czech Brain Aging Study underwent structural MRI and aSN testing in real-space arena setting. Hippocampal and BF nuclei volumes and entorhinal cortex and PFC thickness were obtained. Associations between brain regions involved in aSN were assessed using MANOVA and complex model of mutual relationships was built using structural equation modelling (SEM). Results: Path analysis based on SEM modeling revealed that BF Ch1-2, Ch4p, and Ch4ai nuclei volumes were indirectly associated with aSN performance through MTL (pch1 - 2 = 0.039; pch4p = 0.042) and PFC (pch4ai = 0.044). In the E4 negative group, aSN was indirectly associated with Ch1-2 nuclei volumes (p = 0.015), while in the E4 positive group, there was indirect effect of Ch4p nucleus (p = 0.035). Conclusion: Our findings suggest that in older adults without dementia, BF nuclei affect aSN processing indirectly, through MTL and PFC, and that APOE E4 moderates these associations.

TOWARDS IMPLEMENTATION OF COMPONENT-BASED MODELING IN THE PLATFORM FOR CREATING KNOWLEDGE-BASED SYSTEMS

В статье исследуются проблемы автоматизации и интеллектуальной поддержки процесса математического и имитационного моделирования сложных объектов за счёт комбинации компонентно-ориентированного и онтологического подходов. В качестве основной прикладной области для применения обсуждаемых методов и средств предполагается использовать такое направление, как комплексное моделирование окружающей среды. В контексте изучаемых вопросов рассмотрены современные подходы к автоматизации компонентно-ориентированного моделирования. При интеграции компонентов-моделей в единую результирующую комплексную модель разработчику необходимо не только обеспечить формальное согласование со стандартами используемого каркаса моделирования, но и учитывать различные типы семантической и синтаксической неоднородности компонентов. В связи с этим выполнена классификация типов интеграции комплексных моделей, обсуждаются особенности реализации компонентно-ориентированного моделирования в авторской платформе создания систем, основанных на знаниях. В качестве иллюстративного примера рассматривается гидролого-экологическая балансовая модель. The article considers the problems of automation and intellectual support of the mathematical and simulation modeling process of complex objects via a combination of component-based and ontological approaches. As the main application area for the discussed methods and tools, it is proposed to use the integrated environmental modeling domain. In this context, modern approaches to the automation of component-based modeling are considered. To couple model components into a final complex model, the developer needs not only to ensure formal agreement with the standards of the modeling framework but also to take into account various types of semantic and syntactic heterogeneity of components. In this regard, the classification of the integration types for complex modeling is carried out, the related implementation features in the author's platform for creating knowledge-based systems are discussed. The hydrological-ecological balance model is considered an illustrative example.

КАРКАСНА МОДЕЛЬ РОЗТЯГУВАННЯ КУЛІРНОГО ТРИКОТАЖУ ВЗДОВЖ ПЕТЕЛЬНИХ РЯДІВ

Purpose. The purpose of this study is to develop a mathematical description of the transformation of the frame model of weft-knits under the action of tensile forces in the courswise direction for further three-dimensional modeling of the knited structure.Methodology. Methods of theoretical analysis and synthesis, basics of knitting theory, methods of geometric modeling and parameterization were used in the research process.Findings. Considering the knitwear stretching during the use of the clothing is one of the determining factors of the quality of design decisions. When stretching the weft-knitted fabrics in the coursewise direction, the configuration of its individual stitches’ changes, as well as the thread’s cross-section due to the force interaction between the adjacent structure elements. To simulate the physical and mechanical behavior of knitwear under the stretching, it is suggested using a complex model of knitwear deformation, that includes the suggested frame model of uniaxial coursewise stretching of knitted fabrics. An algorithm for constructing a frame model of stretching a sample of knitted fabric in the coursewise direction is described in the paper. The algorithm is based on the structure parameters, including the wale spacing and course spacing in a dry relaxed state, the relative elongation of the sample at the time of modeling, number of wales and courses in the sample, the coefficient of courses narrowing. Scientific novelty. The paper investigates the features of the transformation of the knitting structure during stretching in the coursewise direction and offers algorithmic and mathematical support for the automated generation of the mesh frame in the context of three-dimensional modeling, which provides for the possibility of considering the dynamics of deformation of knitted fabric undergoing tensile deformations.Practical value. Frame model of the weft-knits deformation and algorithm of mesh-frame construction suggested in the paper, form the basis for determination of coordinates of characteristic points of the structural elements of the knit in a state of uniaxial tension for construction of a three-dimensional model of thread a deformed knitted fabric.

Competing C–H and C–F bond activation reactions of a fluorinated olefin at Rh: a fluorido vinylidene complex as an intermediate in an unprecedented dehydrofluorination step

Dehydrofluorination of a fluorinated vinyl ligand takes place after C–H bond activation of Z-1,3,3,3-tetrafluropropene at a rhodium vinyl complex. Model studies support a vinylidene as reaction intermediate for the dehydrofluorination.

Assessment of the level of the legal component of the economic security of the organization

In modern realities, organizations face various risks, threats of both external and internal nature, which, if implemented, can have a negative impact on the overall condition of the enterprise, and in particular on the functional components of economic security. The article identifies the key components of the economic security of the organization, assesses the level of the legal component of economic security based on the calculation of the values of individual indicators in a complex model.

Сonstruction of regression models for developing the technology to obtain tablets based on medicinal ginger

Scientific research in pharmacy, due to their multifactorial nature, is closely related to modeling of complex static systems. For this purpose, the so-called “input-output” mathematical models, which are built based on the results of the experiment, are widely used. Modeling of static systems based on the experimental data requires the solution of three interrelated tasks: planning of the experiment and its implementation; identification of the model structure and its parameters; approximation, if necessary, of a complex model to a simpler mathematical description.

Internet of Things Technology of Imagine Processing for Smart House

The article considers the image processing, detection of human faces and the transfer of relevant information in MATLAB software. During the rapid global process of industrialization and globalization, elements of smart homes for personal use are becoming popular in production and offices. Life and personal information security is the most important requirement and task of current and future Internet of Things solutions. Therefore, the system of recognizing objects, including people, is relevant and still one that can be qualitatively improved. The processing begins with a state file, which can be replaced by real-time systems, after receiving information from video — is selected in groups of points, which are the corresponding arrays of information. Arrays contains numbers which indicate whether a human face in front of the camera. The data is calibrated to avoid false detection with median distribution. As a result of involving graphic additions, the user can observe in real time where and how many faces are in front of the camera. MATLAB was chosen as the programming environment, because the program includes built-in blocks that allow you to easily combine the mathematical and applied part of the proposed solution. As a result of modeling a complex model was obtained that is able to process the image and determine the necessary elements and objects in the image. This model can be used to track changes in position in space, any, object or objects depending on their size or physical characteristics. A feature of the proposed method is the ability to calibrate and optimize the mathematical model depending on the physical parameters of the system and the required information at the output of the system.