Intrathymic development of committed progenitor (pro)-T cells from multipotent hematopoietic precursors offers an opportunity to dissect the molecular circuitry establishing cell identity in response ...to environmental signals. This transition encompasses programmed shutoff of stem/progenitor genes, upregulation of T cell specification genes, proliferation, and ultimately commitment. To explain these features in light of reported cis-acting chromatin effects and experimental kinetic data, we develop a three-level dynamic model of commitment based upon regulation of the commitment-linked gene Bcl11b. The levels are (1) a core gene regulatory network (GRN) architecture from transcription factor (TF) perturbation data, (2) a stochastically controlled chromatin-state gate, and (3) a single-cell proliferation model validated by experimental clonal growth and commitment kinetic assays. Using RNA fluorescence in situ hybridization (FISH) measurements of genes encoding key TFs and measured bulk population dynamics, this single-cell model predicts state-switching kinetics validated by measured clonal proliferation and commitment times. The resulting multi-scale model provides a mechanistic framework for dissecting commitment dynamics.
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•A multi-level dynamical model is developed for the commitment of T cell precursors•It links gene networks, single-cell RNA analysis, chromatin changes, and cell division•It provides quantitative understanding of commitment kinetic requirements•The model predictions are verified against new clonal and real-time imaging data
Olariu et al. use computational modeling and live-cell developmental imaging to explain the kinetics of early T cell lineage commitment. An integrated computational multi-scale model incorporating gene network architecture, single-cell RNA levels, chromatin state shifts, and proliferation is developed, explored, and validated.
Protein signaling networks among cells play critical roles in a host of pathophysiological processes, from inflammation to tumorigenesis. We report on an approach that integrates microfluidic cell ...handling, in situ protein secretion profiling, and information theory to determine an extracellular protein-signaling network and the role of perturbations. We assayed 12 proteins secreted from human macrophages that were subjected to lipopolysaccharide challenge, which emulates the macrophage-based innate immune responses against Gram-negative bacteria. We characterize the fluctuations in protein secretion of single cells, and of small cell colonies (n = 2, 3,···), as a function of colony size. Measuring the fluctuations permits a validation of the conditions required for the application of a quantitative version of the Le Chatelier's principle, as derived using information theory. This principle provides a quantitative prediction of the role of perturbations and allows a characterization of a protein-protein interaction network.
The growing number of installed photovoltaic (PV) plants is making the simulation of their behavior and their effects on the power network more and more relevant. In this context, an accurate yet ...simple model of the panels is beneficial for evaluating the power production as well as the system efficiency in off-line and on-line analysis. In the preliminary design stages of large plants, this kind of model can support design and decision making, allowing for the simulation of the entire plant and the testing of various power architectures. During the operation, such models may support monitoring, diagnostic, and control functions. In this paper, a model of PV panel, suitable for the aforementioned applications, is presented together with a simple procedure for the identification of its parameters. The critical issues related to the measurement and the estimation of the required environmental quantities are analyzed together with their main metrological requirements. Finally, the experimental validation of the proposed model and algorithms is presented using as a case study the estimation of the energy production of a domestic solar plant.
Three-terminal (3T) GaInP/GaAs solar cells are fabricated from inverted-grown monolithic tandems and processed with external metal contacts suitable for easy interconnection. Prototype 3T tandems ...both with and without tunnel junctions are demonstrated. They are characterized as a function of two independent variables in a variety of configurations, with each configuration holding one of the contacts common to two source-meter units (SMUs). Each of these different measurement configurations completely characterizes the device by transforming the results into 6 unique device parameters and plotting the total power parametrically in two dimensions. The performance is fit using a 3T optoelectronic model that includes luminescent coupling as well as important resistances. Eight of these devices are interconnected in various voltage-constrained configurations to form voltage-matched (VM) strings. Measurement and analysis of these III-V devices and strings are generally applicable to all 3T photovoltaics.
The main drawback of photovoltaic (PV) laser power converters based on GaAs material is the low output voltage, which is often insufficient to power electronic circuits directly. Aside from the use ...of a dc-dc converter in combination with a single PV converter, it is possible to boost the voltage by the monolithic serial interconnection of several converter segments on a single chip, often called multiple converters. Another novel approach introduced in this paper is a multijunction PV cell, where several subcells of the same material are stacked onto a substrate and interconnected by interband tunnel diodes. This paper explores a tandem GaAs-GaAs converter and compares the results with a 2-V multiple PV converter under monochromatic laser illumination. In addition, 4-V multiple PV converters with maximum monochromatic efficiencies (810 nm) of up to 50.1% at 51.6 W/cm 2 and 6-V converters are investigated. Thereby, the fabrication technology of the devices is outlined and the influence of inhomogeneous illumination on the performance of these energy converters is discussed.
In Escherichia coli, protein degradation in synthetic circuits is commonly achieved by the ssrA‐tagged degradation system. In this work, we show that the degradation kinetics for the green ...fluorescent protein fused with the native ssrA tag in each cell exhibits the zeroth‐order limit of the Michaelis–Menten kinetics, rather than the commonly assumed first‐order. When measured in a population, the wide distribution of protein levels in the cells distorts the true kinetics and results in a first‐order protein degradation kinetics as a population average. Using the synthetic gene‐metabolic oscillator constructed previously, we demonstrated theoretically that the zeroth‐order kinetics significantly enlarges the parameter space for oscillation and thus enhances the robustness of the design under parametric uncertainty.
Measurements of Six-Junction Concentrator Solar Cells Geisz, John F.; France, Ryan M.; Steiner, Myles A. ...
2019 IEEE 46th Photovoltaic Specialists Conference (PVSC),
2019-June-16, Volume:
2
Conference Proceeding
Accurate measurements of six-junction inverted metamorphic concentrator solar cells under AM1.5 direct spectrum are obtained by adjusting the spectrum of a tunable high-intensity solar simulator with ...custom mirrors. Isotype reference cells and broadband InGaAs QE calibration cells were developed for accurate measurements. Modeling and varying the illumination show that an unavoidable 15% - 17% overillumination on the sixth junction does not result in significant error of these 6J IMM devices. Spectrally adjusted flash measurements are independently confirmed by NREL's Cell and Module Performance team. Concentration measurements of a 6J IMM solar cell resulted in 47.1 ± 3.2% (absolute) efficiency at 143 suns.
The Back Cover picture shows a scheme of the improved ATP microbiosensor based on poly(benzoxazine) entrapment of enzymes for the detection of ATP at mechanically stimulated osteoblastic cells. More ...information can be found in the Article by C. Kranz and co‐workers on page 864 in Issue 4, 2017 (DOI: 10.1002/celc.201600765).
The availability of gene expression data at the single cell level makes it possible to probe the molecular underpinnings of complex biological processes such as differentiation and oncogenesis. ...Promising new methods have emerged for reconstructing a progression 'trajectory' from static single-cell transcriptome measurements. However, it remains unclear how to adequately model the appreciable level of noise in these data to elucidate gene regulatory network rewiring. Here, we present a framework called Single Cell Inference of MorphIng Trajectories and their Associated Regulation (SCIMITAR) that infers progressions from static single-cell transcriptomes by employing a continuous parametrization of Gaussian mixtures in high-dimensional curves. SCIMITAR yields rich models from the data that highlight genes with expression and co-expression patterns that are associated with the inferred progression. Further, SCIMITAR extracts regulatory states from the implicated trajectory-evolvingco-expression networks. We benchmark the method on simulated data to show that it yields accurate cell ordering and gene network inferences. Applied to the interpretation of a single-cell human fetal neuron dataset, SCIMITAR finds progression-associated genes in cornerstone neural differentiation pathways missed by standard differential expression tests. Finally, by leveraging the rewiring of gene-gene co-expression relations across the progression, the method reveals the rise and fall of co-regulatory states and trajectory-dependent gene modules. These analyses implicate new transcription factors in neural differentiation including putative co-factors for the multi-functional NFAT pathway.
Using a microfluidics device, fluorescence of a recorder (mCherry or mVenus) gene driven by a clock-controlled gene-2 promoter (ccg-2p) was measured simultaneously on over 1000 single cells of ...Neurospora crassa every half hour for 10 days under each of varied light and temperature conditions. Single cells were able to entrain to light over a wide range of day lengths, including 6, 12, or 36 h days. In addition, the period of oscillations in fluorescence remained remarkably stable over a physiological range of temperatures from 20 °C to 30 °C (Q 10 = 1.00-1.07). These results provide evidence of an autonomous clock in most single cells of N. crassa. While most cells had clocks, there was substantial variation between clocks as measured by their phase, raising the question of how such cellular clocks in single cells phase-synchronize to achieve circadian behavior in eukaryotic systems at the macroscopic level of 10 7 cells, where most measurements on the clock are performed. Single cells were placed out of phase by allowing one population to receive 6 or 12 h more light before lights out (D/D). The average phase difference was reduced in the mixed population relative to two unmixed control populations.
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