Moment-based analysis of biochemical networks in a heterogeneous population of communicating cells

Cells can utilize chemical communication to exchange information and coordinate their behavior in the presence of noise. Communication can reduce noise to shape a collective response, or amplify noise to generate distinct phenotypic subpopulations. Here we discuss a moment-based approach to study how cell-cell communication affects noise in biochemical networks that arises from both intrinsic and extrinsic sources. We derive a system of approximate differential equations that captures lower-order moments of a population of cells, which communicate by secreting and sensing a diffusing molecule. Since the number of obtained equations grows combinatorially with number of considered cells, we employ a previously proposed model reduction technique, which exploits symmetries in the underlying moment dynamics. Importantly, the number of equations obtained in this way is independent of the number of considered cells such that the method scales to arbitrary population sizes. Based on this approach, we study how cell-cell communication affects population variability in several biochemical networks. Moreover, we analyze the accuracy and computational efficiency of the moment-based approximation by comparing it with moments obtained from stochastic simulations.Comment: 6 pages, 5 Figure

Characterization of New TPS Resins

Ablative thermal protection systems are commonly used as protection from the intense heat during re-entry of a space vehicle and have been used successfully on many missions including Stardust and Mars Science Laboratory both of which used PICA a phenolic based ablator. Historically, phenolic resin has served as the ablative polymer for many TPS systems. However, it has limitations in both processing and properties such as char yield, glass transition temperature and char stability. Therefore alternative high performance polymers are being considered such as: cyanate ester resin, polyimide, polybenzoxazine (PBZ), and polyimidazole (PBI).Thermal and mechanical properties of these four resin systems were characterized and compared with phenolic resin

How Can Government Increase R&D Activities in the Philippines?

How significant is research and development (R&D) in the Philippines` overall economic development? What drives firms to locate (or not locate) their R&D activities in the country? What barriers, if any, hinder the conduct of innovative activities in the Philippines? How can the Philippines attract more R&D investments and minimize the obstacles to innovation?Philippines, research and development (R&D), R&D activities

SSF: subsidies, a potential bright spot

The WTO negotiations on fisheries subsidies can help conservation and sustainable exploitation efforts as well as ensure the well-being of fishing communities around the worl

Building synthetic multicellular systems from the bottom-up

Biological cell populations, such as in tissues or microbial communities, are constantly subject to different sources of noise and variability. Despite this, multicellular systems are still able to function properly because cells coordinate with each other by communication. Using biological model systems to study this multiscalar process can be challenging because of their innate complexity. In this thesis, we address this challenge by building a synthetic multicellular system using bottom-up in vitro assembly approaches. Using this platform, we aim to study the effect of cell-to-cell communication to population variability in a minimal and simplified context. To achieve this, we require a synthetic cell population with (i) quantifiable gene expression dynamics, (ii) customizable population variability, and (iii) intercellular communication. Having these characteristics will allow us to test different initial configurations of population variability and monitor population gene expression dynamics with and without cell-to-cell communication. To generate these synthetic cell populations, reconstituted cell-free expression systems (CFES) are encapsulated into monodisperse-sized liposomes using double-emulsion microfluidics. Both transcription and translation levels are simultaneously monitored and quantified to develop models of cell-free gene expression dynamics and differentiate between bulk and encapsulated formats. Population variability was then incorporated by combining different batches of cells to create distinct subpopulations or by using a two-inlet double-emulsion microfluidic device to generate single populations with a large dispersion of encapsulated DNA template. Lastly, genetic circuits based on the quorum sensing system of Vibrio fischeri are used to implement diffusion-mediated intercellular signalling. Quorum sensing gene circuits in Escherichia coli extract-based CFES were tested in bulk and phase transfer-generated synthetic cells. Together with these experimental systems, corresponding models of synthetic cell populations that can account for population variability and secrete-and-sensing communication are developed using mixed-effects models and moment dynamics. Overall, this work leverages CFES and microfluidic technologies to reproducibly generate a simplified in vitro model of multicellular systems that can be easily monitored spatiotemporally to study multi-scalar processes.:Preface Chapter 1 Bottom-up multicellular systems Chapter 2 Building blocks: cell-free expression and liposomes Chapter 3 Gene expression dynamics in synthetic cell populations Chapter 4 Variability and communication in synthetic cell populations Chapter 5 Modeling variability & communication in synthetic cell populations Summary and outlook Appendices BibliographyBiologische Zellpopulationen, z.B. in Geweben oder mikrobiellen Gemeinschaften, sind ständig verschiedenen Quellen von Rauschen und Variabilität ausgesetzt. Trotzdem sind multizelluläre Systeme in der Lage, ordnungsgemäß zu funktionieren, weil sich die Zellen durch Kommunikation miteinander abstimmen. Die Verwendung biologischer Modellsysteme zur Untersuchung dieses multiskalaren Prozesses kann aufgrund ihrer angeborenen Komplexität eine Herausforderung darstellen. In dieser Arbeit gehen wir diese Herausforderung an, indem wir ein synthetisches multizelluläres System mit Hilfe von Bottom-up-in vitro-Assembly-Ansätzen aufbauen. Mit Hilfe dieser Plattform wollen wir die Auswirkungen der Kommunikation von Zelle zu Zelle auf die Populationsvariabilität in einem minimalen und vereinfachten Kontext untersuchen. Um dies zu erreichen, benötigen wir eine synthetische Zellpopulation mit (i) quantifizierbarer Genexpressionsdynamik, (ii) anpassbarer Populationsvariabilität und (iii) interzellulärer Kommunikation. Mit diesen Eigenschaften können wir verschiedene Ausgangskonfigurationen der Populationsvariabilität testen und die Genexpressionsdynamik der Population mit und ohne Zell-zu-Zell-Kommunikation beobachten. Um diese synthetischen Zellpopulationen zu erzeugen, werden rekonstituierte zellfreie Expressionssysteme (CFES) mit Hilfe der Doppelemulsions-Mikrofluidik in monodisperse Liposomen eingekapselt. Sowohl die Transkriptions- als auch die Translationsraten werden gleichzeitig überwacht und quantifiziert, um Modelle für die Dynamik der zellfreien Genexpression zu entwickeln und zwischen Bulk- und verkapselten Formaten zu unterscheiden. Die Variabilität der Populationen wurde dann durch die Kombination verschiedener Zellchargen zur Bildung unterschiedlicher Subpopulationen oder durch die Verwendung einer mikrofluidischen Doppelemulsionsvorrichtung mit zwei Einlässen zur Erzeugung einzelner Populationen mit einer großen Streuung der eingekapselten DNA-Vorlage einbezogen. Schließlich werden genetische Schaltkreise auf der Grundlage des Quorum-Sensing-Systems von Vibrio fischeri verwendet, um diffusionsvermittelte interzelluläre Signalübertragung zu implementieren. Quorum-Sensing-Genkreisläufe in CFES auf der Basis von Escherichia coli-Extrakten wurden in synthetischen Zellen getestet, die durch Bulk- und Phasentransfer erzeugt wurden. Zusammen mit diesen experimentellen Systemen wurden entsprechende Modelle synthetischer Zellpopulationen entwickelt, die die Populationsvariabilität und die Sekretions- und Sensing-Kommunikation mit Hilfe von Mixed-Effects-Modellen und Momentendynamik berücksichtigen können. Insgesamt nutzt diese Arbeit CFES- und Mikrofluidik-Technologien, um reproduzierbar ein vereinfachtes in vitro-Modell multizellulärer Systeme zu erzeugen, das leicht raum-zeitlich überwacht werden kann, um multiskalare Prozesse zu untersuchen.:Preface Chapter 1 Bottom-up multicellular systems Chapter 2 Building blocks: cell-free expression and liposomes Chapter 3 Gene expression dynamics in synthetic cell populations Chapter 4 Variability and communication in synthetic cell populations Chapter 5 Modeling variability & communication in synthetic cell populations Summary and outlook Appendices Bibliograph

Droge v. AAAA Two Star Towing, Inc., 136 Nev. Adv. Op. 33 (Jun. 18, 2020)

The Court determined that the test to determine if there was breach of the peace while undertaking self-help repossession considers: (1) repossession occurs at a reasonable time, (2) in a reasonable manner, and (3) that the objectives for self-help repossession are balanced to minimize violence in the act of and attempt to repossess. The Court also determined that the recovery from breach of peace in self-help repossession need not be brought only under NRS 104.9625. Recovery may be sought through a tort-based breach of peace claim

The First But Hopefully Not the Last: How The Last Of Us Redefines the Survival Horror Video Game Genre

For this study, I applied generic criticism, which looks at how a text subverts and adheres to patterns and formats in its respective genre, to analyze how The Last of Us redefined the survival horror video game genre through its narrative. Although some tropes are present in the game and are necessary to stay tonally consistent to the genre, I argued that much of the focus of the game is shifted from the typical situational horror of the monsters and violence to the overall narrative, effective dialogue, strategic use of cinematic elements, and character development throughout the course of the game. I also found that the game challenges notions of masculinity and femininity and takes inspiration from Bildungsroman, which are coming-of-age novels. I proposed a new genre called “Zombie Drama” which refers to texts that focus on character development in a zombie world backdrop. Next, I deconstructed the visual and auditory aspects of the game and how they contribute to the overall construction of the narrative. Lastly, I covered the filmic influences of The Last of Us and drew connections between the texts and the game

Space and surface power for the space exploration initiative: Results from project outreach

The analysis and evaluations of the Space and Surface Power panel, one of eight panels created by RAND to screen and analyze submissions to the Space Exploration Initiative (SEI) Outreach Program, is documented. In addition to managing and evaluating the responses, or submissions, to this public outreach program, RAND conducted its own analysis and evaluation relevent to SEI mission concepts, systems, and technologies. The Power panel screened and analyzed submissions for which a substantial portion of the concepts involved power generation sources, transmission, distribution, thermal management, and handling of power (including conditioning, conversion, packaging, and enhancements in system components). A background discussion of the areas the Power panel covered and the issues the reviewers considered pertinent to the analysis of power submissions are presented. An overview of each of the highest-ranked submissions and then a discussion of these submissions is presented. The results of the analysis is presented