493,960 research outputs found

    Optimal localization patterns in bacterial protein synthesis

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    In Escherichia coli\textit{Escherichia coli} bacterium, the molecular compounds involved in protein synthesis, messenger RNAs (mRNAs) and ribosomes, show marked intracellular localization patterns. Yet a quantitative understanding of the physical principles which would allow one to control protein synthesis by designing, bioengineering, and optimizing these localization patterns is still lacking. In this study, we consider a scenario where a synthetic modification of mRNA reaction-diffusion properties allows for controlling the localization and stoichiometry of mRNAs and polysomes\mathrm{-}complexes of multiple ribosomes bound to mRNAs. Our analysis demonstrates that protein synthesis can be controlled, e.g., optimally enhanced or inhibited, by leveraging mRNA spatial localization and stoichiometry only, without resorting to alterations of mRNA expression levels. We identify the physical mechanisms that control the protein-synthesis rate, highlighting the importance of colocalization between mRNAs and freely diffusing ribosomes, and the interplay between polysome stoichiometry and excluded-volume effects due to the DNA nucleoid. The genome-wide, quantitative predictions of our work may allow for a direct verification and implementation in cell-biology experiments, where localization patterns and protein-synthesis rates may be monitored by fluorescence microscopy in single cells and populations

    Declining Volatility, a General Property of Disparate Systems: From Fossils, to Stocks, to the Stars

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    There may be structural principles pertaining to the general behavior of systems that lead to similarities in a variety of different contexts. Classic examples include the descriptive power of fractals, the importance of surface area to volume constraints, the universality of entropy in systems, and mathematical rules of growth and form. Documenting such overarching principles may represent a rejoinder to the Neodarwinian synthesis that emphasizes adaptation and competition. Instead, these principles could indicate the importance of constraint and structure on form and evolution. Here we document a potential example of a phenomenon suggesting congruent behavior of very different systems. We focus on the notion that universally there has been a tendency for more volatile entities to disappear from systems such that the net volatility in these systems tends to decline. We specifically focus on origination and extinction rates in the marine animal fossil record, the performance of stocks in the stock market, and the characters of stars and stellar systems. We consider the evidence that each is experiencing declining volatility, and also consider the broader significance of this.Comment: Accepted for publication in Palaeontology. 13 pages, 3 figure

    Production of high yield gold/gold-sulfide nanoparticles via cellulose membrane.

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    The properties of gold nanoparticles (GNP) holds promising potential for drug delivery, diagnostics, plasmonic photothermal therapy of diseases, electronics, catalysis, and photovoltaics (Liu et al., 2006; Huang et al., 2003; Thompson, 2007; Atwater and Polman, 2010). This field is growing at a fast pace with the demand for GNPs ever increasing with slow progress on development of synthesis techniques. The objective of this study was to develop a new synthesis technique that produces gold/gold sulfide (GGS) nanoparticles with a high yield. This process can control the equilibrium shift of the surface plasmon resonance (SPR) of the nanoparticles (Patel, 2012). The goal of this research is to increase the total volume of GGS nanoparticles to be synthesized while keeping their tunability for the SPR absorption peak. This research has demonstrated the ability of cellulose membrane to reduce the need for purification steps, which are associated with traditional synthesis techniques for removing small colloidal gold (\u3c 10 nm). It was found that controlling the surface area to volume ratio (SA/Vol) of the cellulose to GGS solution and temperature of the synthesis process, would provide, greater control over the SPR peak. Using these principles allows for larger volume synthesis to be performed while still retaining the ability to tune the SPR peak. It was also discovered that dialyzing out ions during the synthesis process makes bare GGS nanoparticles more stable over time. The time for the reaction to reach equilibrium was observed and showed an increase in temperature and/or SA/Vol reduces the reaction time. In conclusion, this study demonstrated how increasing the temperature and SA/Vol shifts the SPR peak and reduces the time for the reaction to reach equilibrium

    Nano-enabled synthetic biology: A cell mimic based sensing platform for exploiting biochemical networks

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    Exploring and understanding how the smallest scale features of a cell affect biochemical reactions has always been a challenge. Nanoscale fabrication advancements have allowed scientists to create small volume reaction containers that resemble the physical scale of cell membranes. Engineers seek to use biological design principles to manipulate information and import new functionality to such synthetic devices, which in turn, play a crucial role in allowing them to explore the effects of physical transport and extreme conditions of temperature and pH on reaction systems. Engineered reaction containers can be physically and chemically defined to control the flux of molecules of different sizes and charge. The design and testing of such a container is described here. It has a volume of 19 pL and has defined slits of 10-200 nm. The device successfully contains DNA and protein molecules and has been used to conduct and analyze enzyme reactions under different substrate concentrations and a continuous cell-free protein synthesis. The effect of DNA concentration and slit size on protein yield is also discussed. Glucose oxidase and horseradish peroxidase were loaded in the small volume container and fed with a solution containing glucose and Amplex Red™ to produce Resorufin. Fluorescent microscopy was used to monitor the reaction, which was carried out under microfluidic control. Enzyme kinetics were characterized and compared with conventional scale results. Continuous cell free protein synthesis in arrays of nanoporous, picoliter volume containers has also been achieved. A multiscale fabrication process allows for the monolithic integration of the containers and an addressable microfluidic network. Synthesis of enhanced green fluorescent protein (eGFP) in the nanoporous containers continues beyond 24 hours and yields more than twice the amount of protein, on a per volume basis, than conventional scale batch reactions. These picoliter, nanoporous containers provide new ways for quick determination of enzyme kinetics and continuous protein synthesis in microfluidic systems. They can be used in a wide variety of applications such as drug discovery, clinical diagnostics and high-throughput screening

    Kant on Perception, Experience and Judgements Thereof

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    It is commonly thought that the distinction between subjectively valid judgements of perception and objectively valid judgements of experience in the Prolegomena is not consistent with the account of judgement Kant offers in the B Deduction, according to which a judgement is ‘nothing other than the way to bring given cognitions to the objective unity of apperception’. Contrary to this view, I argue that the Prolegomena distinction maps closely onto that drawn between the mathematical and dynamical principles in the System of Principles: Kant’s account of the Prolegomena distinction strongly suggests that it is the Analogies of Experience that make it possible for judgements of perception to give rise to judgements of experience. This means that judgements of perception are objectively valid with regard to the quantity and quality of objects, and subjectively valid with regard to the relation they posit between objects. If that is the case, then the notion of a judgement of perception is consistent with the B Deduction account of judgement

    Control of multiscale systems with constraints. 1. Basic principles of the concept of evolution of systems with varying constraints

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    Physical fundamentals of the self-organizing theory for the system with varying constraints are considered. A variation principle, specifically the principle of dynamic harmonization as a generalization of the Gauss-Hertz principle for the systems with varying internal structure is formulated. In compliance with this principle the system evolves through dynamics of the processes leading to harmonization of the internal multiscale structure of the system and its connections with external actions as a result of minimizing the dynamic harmonization function. Main principles of the shell model of self-organization under the action of the dominating entropic disturbance are formulated.Comment: First par

    Are there Many Philosophies or is there Just ‘Doing Philosophy’?

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    The term ‘philosophy’ may be used in more than one sense to refer to both the subjective human activity of ‘doing philosophy’ and its result, namely the production of systems of thought – philosophical theories – which history demonstrates as many and various. It will be argued that there is only one way of doing philosophy and that this is proceeding from the common principles of the human mind in the search for truth of what is real. The mark of true philosophy is unity. A unity of true philosophy may be sought from what seems disparate: Aquinas embodies this effort towards synthesis, convinced that reality is unified and ordered. ‘Just doing philosophy’ is what Thomism embodies
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