Using an agent-based model to analyze the dynamic communication network of the immune response

<p>Abstract</p> <p>Background</p> <p>The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions.</p> <p>Results</p> <p>Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (<it>win</it>) versus persistent infection (<it>loss</it>), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune <it>win </it>outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the <it>loss </it>outcomes.</p> <p>Conclusions</p> <p>An agent-based model capturing several key aspects of complex system dynamics was used to study the emergent properties of the immune response to viral infection. Specific patterns of interactions between leukocyte agents occurring early in the response significantly improved outcome. More interactions at later stages correlated with persistent inflammation and infection. These simulation experiments highlight the importance of commonly overlooked aspects of the immune response and provide insight into these processes at a resolution level exceeding the capabilities of current laboratory technologies.</p

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

Initial recommendations for performing, benchmarking, and reporting single-cell proteomics experiments

Analyzing proteins from single cells by tandem mass spectrometry (MS) has become technically feasible. While such analysis has the potential to accurately quantify thousands of proteins across thousands of single cells, the accuracy and reproducibility of the results may be undermined by numerous factors affecting experimental design, sample preparation, data acquisition, and data analysis. Broadly accepted community guidelines and standardized metrics will enhance rigor, data quality, and alignment between laboratories. Here we propose best practices, quality controls, and data reporting recommendations to assist in the broad adoption of reliable quantitative workflows for single-cell proteomics.Comment: Supporting website: https://single-cell.net/guideline

Control of Adhesion in Carbon Fiber Reinforced Polymeric Composites

Thesis (Ph.D.)--University of Washington, 2023Fiber-reinforced polymeric composites have grown in popularity for use in structural materials due to their low weight, high specific strength, high toughness, customizability, and versatility. A critical element to the performance of composite materials is how well fiber reinforcements adhere to the surrounding polymer matrix. Different applications can benefit from different levels of adhesion, so its control is a crucial element in the design of a composite. One general drawback to the widespread use of composites is that their production with the desired adhesion level is tedious and time-consuming. It was therefore useful to investigate which steps of production might be shortened and what effects this might have on composite properties. It was found that when controlling for the degree of cure, higher temperature and faster curing schedules lead to an increase in fiber-matrix adhesion due to a freezing of internal squeezing stresses. However, the superficial increases of interfacial adhesion would return to baseline levels, but not below, if the polymer matrix was given time at elevated temperatures to anneal, decreasing internal stresses. Additionally, it was found that tertiary cure-acceleratingcompounds increased curing speed while having no deleterious effect on adhesion. Lastly, it was found that fiber handling agents, or sizings, had no noticeable effect on adhesion. Polyolefins have garnered interest for use in fiber-reinforced composites because of their low cost, high toughness, high impact strength, and excellent corrosion resistance. However, they adhere poorly to most substrates, including carbon fibers, leading to poor composite properties. Thus, different techniques to increase polyolefin-carbon fiber adhesion were explored. While most produced only modest improvements, the most promising were the addition of maleic anhydride block co-polymers to the polyolefin (polypropylene) together with the use of 6-azidosulfonylhexyl triethoxysilane to treat carbon fiber surfaces. While increases in interfacial adhesion generally improve composite performance, there are instances where excessive adhesion can result in undesirable properties such as brittleness. Therefore, methods were investigated to tailor interfacial adhesion in carbon fiber-reinforced thermoset composites in an inexpensive, scalable manner. Treatment of the carbon fibers by a room-temperature vulcanizing (RTV) silicone dispersion in a paraffinic solvent (IsoparTM L) produced reductions in adhesion and corresponding increases in toughness in a controlled manner depending on the amount of silicone added. “Charpy” impact toughness for 12k carbon fiber composite tows was approximately doubled with the addition of silicone to the interface, with only limited losses in modulus

Recent progress in non-native nucleic acid modifications

International audienceWhile Nature harnesses RNA and DNA to store, read and write genetic information, the inherent programmability, synthetic accessibility and wide functionality of these nucleic acids make them attractive tools for use in a vast array of applications. In medicine, antisense oligonucleotides (ASOs), siRNAs, and therapeutic aptamers are explored as potent targeted treatment and diagnostic modalities, while in the technological field oligonucleotides have found use in new materials, catalysis, and data storage. The use of natural oligonucleotides limits the possible chemical functionality of resulting technologies while inherent shortcomings, such as susceptibility to nuclease degradation, provide obstacles to their application. Modified oligonucleotides, at the level of the nucleobase, sugar and/or phosphate backbone, are widely used to overcome these limitations. This review provides the reader with an overview of nonnative modifications and the challenges faced in the design, synthesis, application and outlook of novel modified oligonucleotides