A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12

Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales

Disentangling physical activity and sedentary behavior patterns in children with low motor competence

\u3cp\u3eChildren with low motor competence (MC) are at high-risk for physical inactivity, yet little is known about their physical activity (PA) and sedentary behavior (SB) patterns throughout the day. The purpose of this study is to disentangle PA and SB patterns among children with low MC across segmented day periods taking into account differences in gender and age. Data collection took place between May and July 2017. The Athletic Skills Track was used to measure MC. PA levels were objectively measured using accelerometers (ActiGraph, GT3X+) on school days. Data were segmented for (1) time before school, (2) time during school (based on school schedules), and (3) time after school. In total, data from 117 7-to-11 years-old children with low MC were eligible for analyses (N = 58 girls; N = 59 boys). Differences in moderate-to-vigorous PA (MVPA) and SB between segmented periods, gender, and grade were analyzed by ANOVAs with post hoc tests (Tukey) and Independent Sample T-tests respectively. Time spent at school is the major contributor of time spent in SB in children with low MC. Low MC is equally distributed among gender, but large differences exist among boys and girls in both MVPA and SB, indicating low-MC girls as most inactive group. This pattern is found in all segmented periods of the school day, i.e., before, during, and after school. This study stresses the negative contribution of current school curricula on PA and SB in children with low MC, indicating the most efficient period of the day to intervene. Future school-based PA and SB interventions should particularly focus on specific high-risk populations, i.e., children with low MC, and girls in particular.\u3c/p\u3

3D Printed structural electronics:embedding and connecting electronic components into freeform electronic devices

\u3cp\u3eThe need for personalised and smart products drives the development of structural electronics with mass-customisation capability. A number of challenges need to be overcome in order to address the potential of complete free form manufacturing of electronic devices. One key challenge is the integration of conductive structures and components into 3D printed devices by combining different materials and printing techniques that have nearly incompatible printing conditions. In this paper, several methods to integrate electronic circuits and components into a 3D printed structure are discussed. The functional performance of the resulting structures is described. Structural parts were manufactured with a stereolithography-based 3D printing technique, which was interrupted to pick and place electronic components, followed by either direct writing or squeegee filling of conductive material. A thermal curing step was applied to enhance the bonding and improve the electrical performance. Optical micrography, 4-point resistance measurement and cross-sectional analysis were performed to evaluate functionality.\u3c/p\u3