Effects of 3D Geometries on Cellular Gradient Sensing and Polarization

During cell migration, cells become polarized, change their shape, and move in response to various internal and external cues. Cell polarization is defined through the spatio-temporal organization of molecules such as PI3K or small GTPases, and is determined by intracellular signaling networks. It results in directional forces through actin polymerization and myosin contractions. Many existing mathematical models of cell polarization are formulated in terms of reaction-diffusion systems of interacting molecules, and are often defined in one or two spatial dimensions. In this paper, we introduce a 3D reaction-diffusion model of interacting molecules in a single cell, and find that cell geometry has an important role affecting the capability of a cell to polarize, or change polarization when an external signal changes direction. Our results suggest a geometrical argument why more roundish cells can repolarize more effectively than cells which are elongated along the direction of the original stimulus, and thus enable roundish cells to turn faster, as has been observed in experiments. On the other hand, elongated cells preferentially polarize along their main axis even when a gradient stimulus appears from another direction. Furthermore, our 3D model can accurately capture the effect of binding and unbinding of important regulators of cell polarization to and from the cell membrane. This spatial separation of membrane and cytosol, not possible to capture in 1D or 2D models, leads to marked differences of our model from comparable lower-dimensional models.Comment: 31 pages, 7 figure

Smart Waste Collection Processes - A Case Study about Smart Device Implementation

For decades the core processes of collecting waste have been unchanged. Through new IoT-technologies, advances in sensors, and data transfer technologies, data-driven smart waste collection processes will replace old inefficient collection processes. Causing a shift from fix collection intervals to collection on demand, supported by smart algorithms and innovative web-applications. However, implementing such ideas come along with some almost insurmountable challenges related to wireless data transfer, battery lifetime and IoT infrastructure. Therefore, the question arises of how to implement IoT solutions in such complex and challenging environments. In order to contribute to the existing research about smart cities and autonomous IoT devices, we implemented smart devices in glass containers, measuring filling level over several months. The research study’s outcomes are test results, data analysis and a prototype implementation for a reengineered waste collection process. Furthermore, we identified main challenges and key issues which obstruct the implementation and spread of such smart city applications

Single-Cell Migration in Complex Microenvironments: Mechanics and Signaling Dynamics

Cells are highly dynamic and mechanical automata powered by molecular motors that respond to external cues. Intracellular signaling pathways, either chemical or mechanical, can be activated and spatially coordinated to induce polarized cell states and directional migration. Physiologically, cells navigate through complex microenvironments, typically in three-dimensional (3D) fibrillar networks. In diseases, such as metastatic cancer, they invade across physiological barriers and remodel their local environments through force, matrix degradation, synthesis, and reorganization. Important external factors such as dimensionality, confinement, topographical cues, stiffness, and flow impact the behavior of migrating cells and can each regulate motility. Here, we review recent progress in our understanding of single-cell migration in complex microenvironments.National Cancer Institute (U.S.) (Grant No. 5U01CA177799)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award

Multiscale mechanobiology: computational models for integrating molecules to multicellular systems

Mechanical signals exist throughout the biological landscape. Across all scales, these signals, in the form of force, stiffness, and deformations, are generated and processed, resulting in an active mechanobiological circuit that controls many fundamental aspects of life, from protein unfolding and cytoskeletal remodeling to collective cell motions. The multiple scales and complex feedback involved present a challenge for fully understanding the nature of this circuit, particularly in development and disease in which it has been implicated. Computational models that accurately predict and are based on experimental data enable a means to integrate basic principles and explore fine details of mechanosensing and mechanotransduction in and across all levels of biological systems. Here we review recent advances in these models along with supporting and emerging experimental findings.National Cancer Institute (U.S.) (U01-CA177799

Extending Loyalty Programs with BI Functionalities

Effective customer loyalty programs are essential for every company. Small and medium sized brick-and-mortar stores, such as bakeries, butcher and flower shops, often share a common overarching loyalty program, organized by a third-party provider. Furthermore, these small shops have limited resources and often cannot afford complex BI tools. Out of these reasons we investigated how traditional brick-and-mortar stores can benefit from an expansion of service functionalities of a loyalty card provider. To answer this question, we cooperated with a cross-industry customer loyalty program in a polycentric region. The loyalty program was transformed from simple card-based solution to a mobile app for customers and a web-application for shop owners. The new solution offers additional BI services for performing data analytics and strengthening the position of brick-and-mortar stores. Participating shops can work together in order to increase sales and align marketing campaigns. Therefore, shopping data from 12 years, 55 shops, and 19,000 customers was analyzed

Gaylord Produce Removal Machine

This Final Design Review Report outlines the senior design project that began Winter Quarter of 2021 at California Polytechnic State University. Our team consists of three mechanical engineers and a general engineer, working together to design, build, and test a product for Alameda County Food Bank. The goal of the final product is to relieve volunteers and employees of tedious manual labor and increase efficiency during the removal of produce from large Gaylord containers. This document describes background research, the objectives of the project, chosen concept design, analysis and initial prototyping of said concept, the final design, and verification prototype and testing

Prevalence of mental health disorders in inflammatory bowel disease: an Australian outpatient cohort

BACKGROUND: This study aimed to characterize prevalence of anxiety and depressive conditions and uptake of mental health services in an Australian inflammatory bowel disease (IBD) outpatient setting. METHODS: Eighty-one IBD patients (39 males, mean age 35 years) attending a tertiary hospital IBD outpatient clinic participated in this study. Disease severity was evaluated according to the Manitoba Index. Diagnosis of an anxiety or depressive condition was based upon the Mini-International Neuropsychiatric Interview and the Hospital Anxiety and Depression Scale. RESULTS: Based on Hospital Anxiety and Depression Scale subscale scores >8 and meeting Mini-International Neuropsychiatric Interview criteria, 16 (19.8%) participants had at least one anxiety condition, while nine (11.1%) had a depressive disorder present. Active IBD status was associated with higher prevalence rates across all anxiety and depressive conditions. Generalized anxiety was the most common (12 participants, 14.8%) anxiety condition, and major depressive disorder (recurrent) was the most common depressive condition reported (five participants, 6.2%). Seventeen participants (21%) reported currently seeking help for mental health issues while 12.4% were identified has having at least one psychological condition but not seeking treatment. CONCLUSION: We conclude that rates of anxiety and depression are high in this cohort, and that IBD-focused psychological services should be a key component of any holistic IBD service, especially for those identified as having active IBD

Dynamic filopodial forces induce accumulation, damage, and plastic remodeling of 3D extracellular matrices

The mechanical properties of the extracellular matrix (ECM)–a complex, 3D, fibrillar scaffold of cells in physiological environments–modulate cell behavior and can drive tissue morphogenesis, regeneration, and disease progression. For simplicity, it is often convenient to assume these properties to be time-invariant. In living systems, however, cells dynamically remodel the ECM and create time-dependent local microenvironments. Here, we show how cell-generated contractile forces produce substantial irreversible changes to the density and architecture of physiologically relevant ECMs–collagen I and fibrin–in a matter of minutes. We measure the 3D deformation profiles of the ECM surrounding cancer and endothelial cells during stages when force generation is active or inactive. We further correlate these ECM measurements to both discrete fiber simulations that incorporate fiber crosslink unbinding kinetics and continuum-scale simulations that account for viscoplastic and damage features. Our findings further confirm that plasticity, as a mechanical law to capture remodeling in these networks, is fundamentally tied to material damage via force-driven unbinding of fiber crosslinks. These results characterize in a multiscale manner the dynamic nature of the mechanical environment of physiologically mimicking cell-in-gel systems

Formation and optogenetic control of engineered 3D skeletal muscle bioactuators

Densely arrayed skeletal myotubes are activated individually and as a group using precise optical stimulation with high spatiotemporal resolution. Skeletal muscle myoblasts are genetically encoded to express a light-activated cation channel, Channelrhodopsin-2, which allows for spatiotemporal coordination of a multitude of skeletal myotubes that contract in response to pulsed blue light. Furthermore, ensembles of mature, functional 3D muscle microtissues have been formed from the optogenetically encoded myoblasts using a high-throughput device. The device, called “skeletal muscle on a chip”, not only provides the myoblasts with controlled stress and constraints necessary for muscle alignment, fusion and maturation, but also facilitates the measurement of forces and characterization of the muscle tissue. We measured the specific static and dynamic stresses generated by the microtissues and characterized the morphology and alignment of the myotubes within the constructs. The device allows testing of the effect of a wide range of parameters (cell source, matrix composition, microtissue geometry, auxotonic load, growth factors and exercise) on the maturation, structure and function of the engineered muscle tissues in a combinatorial manner. Our studies integrate tools from optogenetics and microelectromechanical systems (MEMS) technology with skeletal muscle tissue engineering to open up opportunities to generate soft robots actuated by a multitude of spatiotemporally coordinated 3D skeletal muscle microtissues.National Science Foundation (U.S.) (Science and Technology Center—Emergent Behaviors of Integrated Cellular Systems (EBICS) grant No. CBET-0939511)National Institutes of Health (U.S.) (EB00262)National Science Foundation (U.S.) (GM74048)National Science Foundation (U.S.) (HL90747)National Institute for Biomedical Imaging and Bioengineering (U.S.) (RESBIO, Integrapted Technologies for Polymeric Biomaterial)University of Pennsylvania. Center for Engineering Cells and RegenerationSingapore-MIT Alliance for Research and Technolog

Implications of therapy interruption on monthly migraine days and modified migraine disability assessment in patients treated with erenumab for chronic and episodic migraine: SQUARE study interim results.

BACKGROUND There are limited real-world data in Switzerland examining the impact of erenumab, a fully human IgG2 monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, on migraine-related quality of life. OBJECTIVE This 18-month interim analysis of 172 patients with episodic or chronic migraine from the SQUARE study provides first prospective insights on the impact of mandatory erenumab treatment interruption, following Swiss-reimbursement requirements, in a real-world clinical setting in Switzerland. FINDINGS Recruited patients receiving 70 or 140 mg erenumab underwent treatment interruption on average 11.2 months after therapy onset with a mean duration of 4 months. There were sustained improvements in mean monthly migraine days (MMD) and migraine disability (mMIDAS) during initial treatment with erenumab. Treatment interruption was associated with a temporary worsening of condition. Symptoms ameliorated upon therapy reuptake reaching improvements similar to pre-break within 3 months. CONCLUSIONS Treatment interruption was associated with a temporary worsening of condition, which improved again after therapy restart