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David A. Garcia

Bio: David A. Garcia is an academic researcher from University of Maryland, College Park. The author has contributed to research in topics: Transcription factor & Dielectric. The author has an hindex of 7, co-authored 12 publications receiving 196 citations. Previous affiliations of David A. Garcia include National Institutes of Health & University of Los Andes.

Papers
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Journal ArticleDOI
03 Jul 2020-Science
TL;DR: It is shown that high-energy ion bombardment improves the energy storage performance of relaxor ferroelectric thin films and suggests that postprocessing may be important for developing the next generation of capacitors.
Abstract: Dielectric capacitors can store and release electric energy at ultrafast rates and are extensively studied for applications in electronics and electric power systems Among various candidates, thin films based on relaxor ferroelectrics, a special kind of ferroelectric with nanometer-sized domains, have attracted special attention because of their high energy densities and efficiencies We show that high-energy ion bombardment improves the energy storage performance of relaxor ferroelectric thin films Intrinsic point defects created by ion bombardment reduce leakage, delay low-field polarization saturation, enhance high-field polarizability, and improve breakdown strength We demonstrate energy storage densities as high as ~133 joules per cubic centimeter with efficiencies exceeding 75% Deterministic control of defects by means of postsynthesis processing methods such as ion bombardment can be used to overcome the trade-off between high polarizability and breakdown strength

149 citations

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TL;DR: It is demonstrated that transcription factor (TF) nuclear mobility determines burst duration, whereas its bound fraction determines burst frequency, and a striking co-bursting pattern between TSs located at proximal and distal positions in the nucleus is uncovered.

79 citations

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TL;DR: In this article, the authors used single-molecule tracking and machine-learning-based classification to directly measure the nuclear mobility of the glucocorticoid receptor (GR) in live cells.

64 citations

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TL;DR: In this paper, the authors highlight the importance of mechanotransduction as one of the governing principles of cancer progression and emphasize the need to conduct further studies of the molecular mechanisms involved in sensing mechanical cues and coordinating transcriptional responses.

53 citations

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TL;DR: In this article, the authors proposed a continuum of affinities model to explain transcription factor (TF) dynamics, which is consistent with complex interactions of TFs with multiple nuclear domains as well as binding and searching on the chromatin template.
Abstract: Single-molecule tracking (SMT) allows the study of transcription factor (TF) dynamics in the nucleus, giving important information regarding the diffusion and binding behavior of these proteins in the nuclear environment. Dwell time distributions obtained by SMT for most TFs appear to follow bi-exponential behavior. This has been ascribed to two discrete populations of TFs-one non-specifically bound to chromatin and another specifically bound to target sites, as implied by decades of biochemical studies. However, emerging studies suggest alternate models for dwell-time distributions, indicating the existence of more than two populations of TFs (multi-exponential distribution), or even the absence of discrete states altogether (power-law distribution). Here, we present an analytical pipeline to evaluate which model best explains SMT data. We find that a broad spectrum of TFs (including glucocorticoid receptor, oestrogen receptor, FOXA1, CTCF) follow a power-law distribution of dwell-times, blurring the temporal line between non-specific and specific binding, suggesting that productive binding may involve longer binding events than previously believed. From these observations, we propose a continuum of affinities model to explain TF dynamics, that is consistent with complex interactions of TFs with multiple nuclear domains as well as binding and searching on the chromatin template.

53 citations


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Journal ArticleDOI
TL;DR: In this article, the fundamental principles of energy storage in dielectric capacitors are introduced and a comprehensive review of the state-of-the-art is presented. But the authors do not consider the use of lead-free materials in high-temperature applications, since their toxicity raises concern over their use in consumer applications.
Abstract: Materials exhibiting high energy/power density are currently needed to meet the growing demand of portable electronics, electric vehicles and large-scale energy storage devices. The highest energy densities are achieved for fuel cells, batteries, and supercapacitors, but conventional dielectric capacitors are receiving increased attention for pulsed power applications due to their high power density and their fast charge-discharge speed. The key to high energy density in dielectric capacitors is a large maximum but small remanent (zero in the case of linear dielectrics) polarization and a high electric breakdown strength. Polymer dielectric capacitors offer high power/energy density for applications at room temperature, but above 100 °C they are unreliable and suffer from dielectric breakdown. For high-temperature applications, therefore, dielectric ceramics are the only feasible alternative. Lead-based ceramics such as La-doped lead zirconate titanate exhibit good energy storage properties, but their toxicity raises concern over their use in consumer applications, where capacitors are exclusively lead free. Lead-free compositions with superior power density are thus required. In this paper, we introduce the fundamental principles of energy storage in dielectrics. We discuss key factors to improve energy storage properties such as the control of local structure, phase assemblage, dielectric layer thickness, microstructure, conductivity, and electrical homogeneity through the choice of base systems, dopants, and alloying additions, followed by a comprehensive review of the state-of-the-art. Finally, we comment on the future requirements for new materials in high power/energy density capacitor applications.

396 citations

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TL;DR: The current understanding of the mechanisms by which pioneer factors initiate gene network changes and will ultimately contribute to the ability to control cell fates at will are focused on.
Abstract: Pioneer transcription factors have the intrinsic biochemical ability to scan partial DNA sequence motifs that are exposed on the surface of a nucleosome and thus access silent genes that are inaccessible to other transcription factors. Pioneer factors subsequently enable other transcription factors, nucleosome remodeling complexes, and histone modifiers to engage chromatin, thereby initiating the formation of an activating or repressive regulatory sequence. Thus, pioneer factors endow the competence for fate changes in embryonic development, are essential for cellular reprogramming, and rewire gene networks in cancer cells. Recent studies with reconstituted nucleosomes in vitro and chromatin binding in vivo reveal that pioneer factors can directly perturb nucleosome structure and chromatin accessibility in different ways. This review focuses on our current understanding of the mechanisms by which pioneer factors initiate gene network changes and will ultimately contribute to our ability to control cell fates at will.

207 citations

Journal ArticleDOI
01 Oct 2021-Science
TL;DR: In this paper, relaxor ferroelectrics characterized by nanodomains are used for energy storage in advanced electronics and high power electrical systems, and they are shown to be fundamental to advanced electronics.
Abstract: Electrostatic energy storage technology based on dielectrics is fundamental to advanced electronics and high-power electrical systems. Recently, relaxor ferroelectrics characterized by nanodomains ...

169 citations

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TL;DR: In this paper, the authors introduce the chemical and synthetic methodologies of 2D conjugated MOFs, intrinsic influences on their electronic structures and charge transport properties, as well as multifunctional applications of this class of materials for MOFtronics and potential power sources for MOFstronics.
Abstract: The 21st century has seen a reinvention of how modern electronics impact our daily lives; silicon-electronics and organic electronics are currently at the core of modern electronics. Recent advances have demonstrated that conductive metal–organic frameworks (MOFs), as another unique class of electronic materials, are emerging to provide additional possibility for multifunctional electronic devices that brings us “MOFtronics”. Typically, two-dimensional conjugated MOFs (2D c-MOFs) are a novel class of layer-stacked MOFs with in-plane extended π-conjugation that exhibit unique properties such as intrinsic porosity, crystallinity, stability, and electrical conductivity as well as tailorable band gaps. Benefiting from their unique features and high conductivity, 2D c-MOFs have displayed great potential for multiple high-performance (opto)electronic, magnetic, and energy devices. In this review article, we introduce the chemical and synthetic methodologies of 2D c-MOFs, intrinsic influences on their electronic structures and charge transport properties, as well as multifunctional applications of this class of materials for MOFtronics and potential power sources for MOFtronics. We highlight the benefits and limitations of thus-far developed 2D c-MOFs from synthesis to function and offer our perspectives in regard to the challenges to be addressed.

160 citations

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TL;DR: A wealth of structural and functional data that have enabled a deeper understanding of Pol II transcription mechanisms are summarized and mechanistic questions that remain unanswered or controversial are highlighted.
Abstract: RNA polymerase II (Pol II) transcribes all protein-coding genes and many noncoding RNAs in eukaryotic genomes. Although Pol II is a complex, 12-subunit enzyme, it lacks the ability to initiate transcription and cannot consistently transcribe through long DNA sequences. To execute these essential functions, an array of proteins and protein complexes interact with Pol II to regulate its activity. In this review, we detail the structure and mechanism of over a dozen factors that govern Pol II initiation (e.g., TFIID, TFIIH, and Mediator), pausing, and elongation (e.g., DSIF, NELF, PAF, and P-TEFb). The structural basis for Pol II transcription regulation has advanced rapidly in the past decade, largely due to technological innovations in cryoelectron microscopy. Here, we summarize a wealth of structural and functional data that have enabled a deeper understanding of Pol II transcription mechanisms; we also highlight mechanistic questions that remain unanswered or controversial.

144 citations