5,194 research outputs found
On Expectations-Driven Business Cycles in Economies with Production Externalities: A Comment
Eusepi (2009, International Journal of Economic Theory 5, pp. 9-23) analytically finds that a one-sector real business cycle model may exhibit positive co-movement between consumption and investment when the equilibrium wage-hours locus is positively-sloped and steeper than the household's labor supply curve. However, we show that this condition does not imply expectations-driven business cycles will emerge in Eusepi's model. Specifically, a positive news shock about future productivity improvement leads to an aggregate recession whereby output, employment, consumption and investment all fall in the announcement period.Expectations-Driven Business Cycles; Production Externalities.
Implementation and System Identification of a Phosphorylation-Based Insulator in a Cell-Free Transcription-Translation System
An outstanding challenge in the design of synthetic biocircuits is the development of a robust and efficient strategy for interconnecting functional modules. Recent work demonstrated that a phosphorylation-based insulator (PBI) implementing a dual strategy of high gain and strong negative feedback can be used as a device to attenuate retroactivity. This paper describes the implementation of such a biological circuit in a cell-free transcription-translation system and the structural identifiability of the PBI in the system. We first show that the retroactivity also exists in the cell-free system by testing a simple negative regulation circuit. Then we demonstrate that the PBI circuit helps attenuate the retroactivity significantly compared to the control. We consider a complex model that provides an intricate description of all chemical reactions and leveraging specific physiologically plausible assumptions. We derive a rigorous simplified model that captures the output dynamics of the PBI. We performed standard system identification analysis and determined that the model is globally identifiable with respect to three critical parameters. These three parameters are identifiable under specific experimental conditions and we performed these experiments to estimate the parameters. Our experimental results suggest that the functional form of our simplified model is sufficient to describe the reporter dynamics and enable parameter estimation. In general, this research illustrates the utility of the cell-free expression system as an alternate platform for biocircuit implementation and system identification and it can provide interesting insights into future biological circuit designs
Galactic accretion and the outer structure of galaxies in the CDM model
We have combined the semi-analytic galaxy formation model of Guo et al.
(2011) with the particle-tagging technique of Cooper et al. (2010) to predict
galaxy surface brightness profiles in a representative sample of ~1900 massive
dark matter haloes (10^12--10^14 M_sol) from the Millennium II Lambda-CDM
N-body simulation. Here we present our method and basic results focusing on the
outer regions of galaxies, consisting of stars accreted in mergers. These
simulations cover scales from the stellar haloes of Milky Way-like galaxies to
the 'cD envelopes' of groups and clusters, and resolve low surface brightness
substructure such as tidal streams. We find that the surface density of
accreted stellar mass around the central galaxies of dark matter haloes is well
described by a Sersic profile, the radial scale and amplitude of which vary
systematically with halo mass (M_200). The total stellar mass surface density
profile breaks at the radius where accreted stars start to dominate over stars
formed in the galaxy itself. This break disappears with increasing M_200
because accreted stars contribute more of the total mass of galaxies, and is
less distinct when the same galaxies are averaged in bins of stellar mass,
because of scatter in the relation between M_star and M_200. To test our model
we have derived average stellar mass surface density profiles for massive
galaxies at z~0.08 by stacking SDSS images. Our model agrees well with these
stacked profiles and with other data from the literature, and makes predictions
that can be more rigorously tested by future surveys that extend the analysis
of the outer structure of galaxies to fainter isophotes. We conclude that it is
likely that the outer structure of the spheroidal components of galaxies is
largely determined by collisionless merging during their hierarchical assemblyComment: Accepted by MNRAS. Shortened following referee's report, conclusions
unchanged. 21 pages, 15 figure
Discussion of 'Estimating time-varying causal excursion effect in mobile health with binary outcomes' by T. Qian et al
We discuss the recent paper on "excursion effect" by T. Qian et al. (2020).
We show that the methods presented have close relationships to others in the
literature, in particular to a series of papers by Robins, Hern\'{a}n and
collaborators on analyzing observational studies as a series of randomized
trials. There is also a close relationship to the history-restricted and the
history-adjusted marginal structural models (MSM). Important differences and
their methodological implications are clarified. We also demonstrate that the
excursion effect can depend on the design and discuss its suitability for
modifying the treatment protocol.Comment: Submitted to Biometrika as an invited discussio
Design Space Exploration of the Violacein Pathway in Escherichia coli Based Transcription Translation Cell-Free System (TX-TL)
In this study, an Escherichia coli (E. coli) based transcription translation cell-free system (TX-TL) was employed to sample various enzyme expression levels of the violacein pathway. The pathway was successfully reconstructed in TX-TL. Its variation produced different metabolites as evident from the extracts assorted colors. Analysis of the violacein product via UV-Vis absorption and liquid chromatography-mass spectrometry (LC-MS) detected 68 nanograms of violacein per 10 microliters reaction volume. Significant buildup of prodeoxyviolacein intermediate was also detected in the equimolar TX-TL reaction. Finally, design space exploration experiments suggested an improvement in violacein production at high VioC and VioD DNA concentrations
Bring Your Own Device (BYOD): Current Status, Issues, and Future Directions
The smart mobile device has emerged as an extension of the self, closely tied to the personal behaviors and preferences. This panel discussion covers the current status, real world cases, adoption, pros/cons, issues (security, privacy), and future direction of the use and adoption of Bring-Your-Own-Device (BYOD). The panel also covers BYOS (Bring-Your-Own-Service) and BYOA (Bring-Your-Own-Apps)
Prototyping And Implementation Of A Novel Feedforward Loop In A Cell-Free Transcription-Translation System And Cells
Building novel synthetic biological devices is a time-consuming task because of the lengthy cell-based testing and optimization processes. Recent progress made in the cell-free field suggests that the utilization of mathematical models and cell-free transcription-translation testing platforms to systematically design and test novel synthetic biocircuits may help streamline some of the processes. Here we present a study of building a novel functional biological network motif from scratch with the aid of the mathematical modeling and the cell-free prototyping. In this work, we demonstrated that we were able to make a 3-promoter feedforward circuit from a concept to a working biocircuit in cells within a month. We started with performing simulations with a cell-free transcription–translation simulation toolbox. After verifying the feasibility of the circuit design, we used a fast assembling method to build the constructs and used the linear DNAs directly in the cell-free system for prototyping. After additional tests and assemblies, we implemented the circuit in plasmid forms in cells and showed that the in vivo results were consistent with the simulations and the outcomes in the cell-free platform. This study showed the usefulness of modeling and prototyping in building synthetic biocircuits and that we can use these tools to help streamline the process of circuit optimizations in future studies
Construction of Incoherent Feedforward Loop Circuits in a Cell-Free System and in Cells
Cells utilize transcriptional regulation networks to respond to environmental signals. Network motifs, such as feedforward loops, play essential roles in these regulatory networks. In this work, we construct two different functional and modular incoherent type 1 feedforward loop circuits in a cell-free transcription–translation system and in cells. With the help of mathematical modeling and the cell-free system, we can streamline the design–build–test cycles of the circuits, in which we characterize and optimize these circuits in vitro to confirm that they function as expected before implementing them in vivo. We show that the performance of these circuits from in vitro studies closely recapitulates those from in vivo experiments. We demonstrate that these feedforward loops show dynamic response and pulse-like behavior both in vitro and in vivo. These novel feedforward loop network motifs can be incorporated in more complicated biological circuits as detectors or responders
Moderate Heat Application Enhances the Efficacy of Nanosecond Pulse Stimulation for the Treatment of Squamous Cell Carcinoma
Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times larger than in cells exposed to nanosecond pulse stimulation at room temperature. Application of moderate heating alone did not cause cell death. A nanosecond pulse stimulation electrode with integrated controllable laser heating was developed to treat murine ectopic squamous cell carcinoma. With this innovative system, we were able to quickly heat and maintain the temperature of the target tumor at 43 degrees C during nanosecond pulse stimulation. Nanosecond pulse stimulation with moderate heating was shown to significantly extend overall survival, delay tumor growth, and achieve a high rate of complete tumor regression. Moderate heating extended survival nearly 3-fold where median overall survival was 22 days for 9.8 kV without moderate heating and over 63 days for tumors pulsed with 600, 100 ns pulses at 5 Hz, at voltage of 9.8 kV with moderate heating. Median overall survival in the control groups was 24 and 31 days for mice with untreated tumors and tumors receiving moderate heat alone, respectively. Nearly 69% (11 of 16) of tumor-bearing mice treated with nanosecond pulse stimulation with moderate heating were tumor free at the completion of the study, whereas complete tumor regression was not observed in the control groups and in 9.8 kV without moderate heating. These results suggest moderate heating can reduce the necessary applied voltage for tumor ablation with nanosecond pulse stimulation
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