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Paßens, M., and S. Karthäuser. "Rotational switches in the two-dimensional fullerene quasicrystal." Acta Crystallographica Section A Foundations and Advances 75, no. 1 (2019): 41–49. http://dx.doi.org/10.1107/s2053273318015681.
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One of the essential components of molecular electronic circuits are switching elements that are stable in two different states and can ideally be switched on and off many times. Here, distinct buckminsterfullerenes within a self-assembled monolayer, forming a two-dimensional dodecagonal quasicrystal on a Pt-terminated Pt3Ti(111) surface, are identified to form well separated molecular rotational switching elements. Employing scanning tunneling microscopy, the molecular-orbital appearance of the fullerenes in the quasicrystalline monolayer is resolved. Thus, fullerenes adsorbed on the 36 vertex configuration are identified to exhibit a distinctly increased mobility. In addition, this finding is verified by differential conductance measurements. The rotation of these mobile fullerenes can be triggered frequently by applied voltage pulses, while keeping the neighboring molecules immobile. An extensive analysis reveals that crystallographic and energetic constraints at the molecule/metal interface induce an inequality of the local potentials for the 36 and 32.4.3.4 vertex sites and this accounts for the switching ability of fullerenes on the 36 vertex sites. Consequently, a local area of the 8/3 approximant in the two-dimensional fullerene quasicrystal consists of single rotational switching fullerenes embedded in a matrix of inert molecules. Furthermore, it is deduced that optimization of the intermolecular interactions between neighboring fullerenes hinders the realization of translational periodicity in the fullerene monolayer on the Pt-terminated Pt3Ti(111) surface.
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Wu, Yaming, Liren Liu, and Zhijiang Wang. "Optical crossbar elements used for switching networks." Applied Optics 33, no. 2 (1994): 175. http://dx.doi.org/10.1364/ao.33.000175.
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Wingreen, Ned S., and Eugen Schenfeld. "Size–speed trade-off in optical switching elements." Applied Optics 34, no. 26 (1995): 5907. http://dx.doi.org/10.1364/ao.34.005907.
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Rajewski, Remigiusz. "The Optical Signal-to-Crosstalk Ratio for the MBA(N, e, g) Switching Fabric †." Sensors 21, no. 4 (2021): 1534. http://dx.doi.org/10.3390/s21041534.
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The banyan-type switching networks, well known in switching theory and called the logdN switching fabrics, are composed of symmetrical switching elements of size d×d. In turn, the modified baseline architecture, called the MBA(N,e,g), is only partially built from symmetrical optical switching elements, and it is constructed mostly from asymmetrical optical switching elements. Recently, it was shown that the MBA(N,e,g) structure requires a lower number of passive as well as active optical elements than the banyan-type switching fabric of the same capacity and functionality, which makes it an attractive solution. However, the optical signal-to-crosstalk ratio for the MBA(N,e,g) was not investigated before. Therefore, in this paper, the optical signal-to-crosstalk ratio in the MBA(N,e,g) was determined. Such crosstalk influences the output signal’s quality. Thus, if such crosstalk is lower, the signal quality is better. The switching fabric proposed in the author’s previous work has lower optical signal losses than a typical Beneš and banyan-type switching networks of this same capacity and functionality, which gives better quality of transmitted optical signals at the switching node’s output. The investigated MBA(N,e,g) architecture also contains one stage fewer than banyan-type network of the same capacity, which is an essential feature from the optical switching point of view.
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Simonović, Svetomir. "SOME PROSPECTIVE ELEMENTS OF A NANOFACTORY." International Journal "Advanced Quality" 45, no. 1 (2017): 41. http://dx.doi.org/10.25137/ijaq.n1.v45.y2017.p41-48.
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Nanomanipulation capabilities of scanning probe devices have progressed in the terms of degree-of-freedom available for manipulation, but problems of durable and badly made nanomanipulation have remained. So, it seems reasonably to use biologically based nanomachines in order to form a nanofactory. In this sense, proteins and DNA or their assemblies can be used as nanomachines or their parts. Motor proteins, DNA walkers and flagella motor are described here as examples thereof, but here the problem of movement control appears. Switching molecular devices are described that can be employed as controllers parts thereof.
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Firth, W., and I. Galbraith. "Diffusive transverse coupling of bistable elements - Switching waves and crosstalk." IEEE Journal of Quantum Electronics 21, no. 9 (1985): 1399–403. http://dx.doi.org/10.1109/jqe.1985.1072842.
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Richardson, Harvey, and Eitan Abraham. "Effect of pixelation on the switching speeds of InSb bistable elements." Journal of the Optical Society of America B 7, no. 6 (1990): 1051. http://dx.doi.org/10.1364/josab.7.001051.
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Luis Galbete, José, Montserrat Buceta, and Nicolas Mermod. "MAR elements regulate the probability of epigenetic switching between active and inactive gene expression." Mol. BioSyst. 5, no. 2 (2009): 143–50. http://dx.doi.org/10.1039/b813657b.
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Kawai-Kowase, Keiko, and Gary K. Owens. "Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells." American Journal of Physiology-Cell Physiology 292, no. 1 (2007): C59—C69. http://dx.doi.org/10.1152/ajpcell.00394.2006.
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Smooth muscle cell (SMC) differentiation is an essential component of vascular development and these cells perform biosynthetic, proliferative, and contractile roles in the vessel wall. SMCs are not terminally differentiated and possess the ability to modulate their phenotype in response to changing local environmental cues. The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms involved in controlling phenotypic switching of SMC with particular focus on examination of processes that contribute to the repression of SMC marker genes. We discuss the environmental cues which actively regulate SMC phenotypic switching, such as platelet-derived growth factor-BB, as well as several important regulatory mechanisms required for suppressing expression of SMC-specific/selective marker genes in vivo, including those dependent on conserved G/C-repressive elements, and/or highly conserved degenerate CArG elements found in the promoters of many of these marker genes. Finally, we present evidence indicating that SMC phenotypic switching involves multiple active repressor pathways, including Krüppel-like zinc finger type 4, HERP, and ERK-dependent phosphorylation of Elk-1 that act in a complementary fashion.
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Huang, Yishen, Qixiang Cheng, Yu-Han Hung, et al. "Multi-Stage 8 × 8 Silicon Photonic Switch Based on Dual-Microring Switching Elements." Journal of Lightwave Technology 38, no. 2 (2020): 194–201. http://dx.doi.org/10.1109/jlt.2019.2945941.
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Yuen, Piu-Hung, and Lian-Kuan Chen. "Optimization of Microring-Based Interconnection by Leveraging the Asymmetric Behaviors of Switching Elements." Journal of Lightwave Technology 31, no. 10 (2013): 1585–92. http://dx.doi.org/10.1109/jlt.2013.2253761.
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GLAW, V., K. JANIAK, A. KUMMROW, V. PENSCHKE, and H. J. EICHLER. "THERMAL RELAXATION TIMES OF BISTABLE THIN FILM ELEMENTS." Journal of Nonlinear Optical Physics & Materials 02, no. 02 (1993): 209–20. http://dx.doi.org/10.1142/s0218199193000127.
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The heat flow in evaporated thin film interference filters with CdS spacer and an optional CdSe absorption layer is investigated, analyzing the dynamics of optical bistability. The influence of the spot radius r of the exciting laser beam on the switching parameters is studied experimentally and theoretically. The response to pulsed excitation of the bistable devices can be described with a relaxation time τ~r and an effective nonlinearity χ~r−2 which is inversely proportional to the heat capacity of the bistable element.
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Christgen, Matthias, Stephan Bartels, Jana L. van Luttikhuizen, et al. "E-cadherin to P-cadherin switching in lobular breast cancer with tubular elements." Modern Pathology 33, no. 12 (2020): 2483–98. http://dx.doi.org/10.1038/s41379-020-0591-3.
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AbstractLoss of E-cadherin expression due to mutation of the CDH1 gene is a characteristic feature of invasive lobular breast cancer (ILBC). Beta-catenin, which binds to the cytoplasmic domain of E-cadherin, is simultaneously downregulated, reflecting disassembly of adherens junctions (AJs) and loss of cell adhesion. E-cadherin to P-cadherin expression switching can rescue AJs and cell adhesion. However, P-cadherin has not been implicated in ILBC, so far. We aimed to characterize 13 ILBCs with exceptional histomorphology, which we termed ILBCs with tubular elements. The CDH1 mutational status was determined by next generation sequencing and whole-genome copy number (CN) profiling. Expression of cadherins was assessed by immunohistochemistry. ILBCs with tubular elements were ER-positive (13/13) and HER2-negative (13/13) and harbored deleterious CDH1 mutations (11/13) accompanied by loss of heterozygosity due to deletion of chromosome 16q22.1 (9/11). E-cadherin expression was lost or reduced in noncohesive tumor cells and in admixed tubular elements (13/13). Beta-catenin expression was lost in noncohesive tumor cells, but was retained in tubular elements (11/13), indicating focal rescue of AJ formation. N-cadherin and R-cadherin were always negative (0/13). Strikingly, P-cadherin was commonly positive (12/13) and immunoreactivity was accentuated in tubular elements. Adjacent lobular carcinoma in situ (LCIS) was always P-cadherin-negative (0/7). In a reference cohort of LCIS specimens, P-cadherin was constantly not expressed (0/25). In a reference cohort of invasive mammary carcinomas, P-cadherin-positive cases (36/268, 13%) were associated with triple-negative nonlobular breast cancer (P < 0.001). Compared with ILBCs from the reference cohort, P-cadherin expression was more common in ILBCs with tubular elements (12/13 versus 7/84, P < 0.001). In summary, E-cadherin to P-cadherin switching occurs in a subset of ILBCs. P-cadherin is the molecular determinant of a mixed-appearing histomorphology in ILBCs with tubular elements.
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Khoo, I. C., Andres Diaz, J. Ding, K. Chen, and Y. Zhang. "Collective and Individual Molecular Nonlinear Photonics of Liquid Crystals." Journal of Nonlinear Optical Physics & Materials 12, no. 02 (2003): 277–89. http://dx.doi.org/10.1142/s0218863503001390.
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This review will examine the origins of nonlinear light scattering processes in nematic liquid crystals, and explore various nonlinear photonic processes associated with optically induced director axis reorientation effects. Our theoretical prediction shows that the upper limit of nematic liquid crystal reorientation nonlinearity can be as high as 1000 cm2/W. The supra-nonlinear responses of nematic liquid crystals enable various self-action or electro-optical guiding, mixing, switching and modulation of light with unprecedented low power thresholds. Owing to the broadband birefringence of NLC, we expect to realize optical elements/devices capable of similar multi-functional operations throughout the visible — infrared regime. We also discuss the optical limiting action of isotropic-phase liquid crystal filled nonlinear fiber arrays.
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Haile, D. J., M. W. Hentze, T. A. Rouault, J. B. Harford, and R. D. Klausner. "Regulation of interaction of the iron-responsive element binding protein with iron-responsive RNA elements." Molecular and Cellular Biology 9, no. 11 (1989): 5055–61. http://dx.doi.org/10.1128/mcb.9.11.5055-5061.1989.
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The 5' untranslated region of the ferritin heavy-chain mRNA contains a stem-loop structure called an iron-responsive element (IRE), that is solely responsible for the iron-mediated control of ferritin translation. A 90-kilodalton protein, called the IRE binding protein (IRE-BP), binds to the IRE and acts as a translational repressor. IREs also explain the iron-dependent control of the degradation of the mRNA encoding the transferrin receptor. Scatchard analysis reveals that the IRE-BP exists in two states, each of which is able to specifically interact with the IRE. The higher-affinity state has a Kd of 10 to 30 pM, and the lower affinity state has a Kd of 2 to 5 nM. The reversible oxidation or reduction of a sulfhydryl is critical to this switching, and the reduced form is of the higher affinity while the oxidized form is of lower affinity. The in vivo rate of ferritin synthesis is correlated with the abundance of the high-affinity form of the IRE-BP. In lysates of cells treated with iron chelators, which decrease ferritin biosynthesis, a four- to fivefold increase in the binding activity is seen and this increase is entirely caused by an increase in high-affinity binding sites. In desferrioxamine-treated cells, the high-affinity form makes up about 50% of the total IRE-BP, whereas in hemin-treated cells, the high-affinity form makes up less than 1%. The total amount of IRE-BP in the cytosol of cells is the same regardless of the prior iron treatment of the cell. Furthermore, a mutated IRE is not able to interact with the IRE-BP in a high-affinity form but only at a single lower affinity Kd of 0.7 nM. Its interaction with the IRE-BP is insensitive to the sulfhydryl status of the protein.
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Okamoto, Masahiro, and Katsuya Hayashi. "Network study of integrated biochemical switching system I: Connection of basic elements." Biosystems 24, no. 1 (1990): 39–52. http://dx.doi.org/10.1016/0303-2647(90)90028-y.
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Harju, Susanna, Kellie J. McQueen та Kenneth R. Peterson. "Chromatin Structure and Control of β-Like Globin Gene Switching". Experimental Biology and Medicine 227, № 9 (2002): 683–700. http://dx.doi.org/10.1177/153537020222700902.
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The human β-globin locus is a complex genetic system widely used for analysis of eukaryotic gene expression. The locus consists of five functional β-like globin genes, ε, Gγ, Aγ, δ, and β, arrayed on the chromosome in the order that they are expressed during ontogeny. Globin gene expression is regulated, in part, by the locus control region, which physically consists of five DNasel-hypersensitive sites located 6-22 Kb upstream of the ε-globin gene. During ontogeny two switches occur in β-globin gene expression that reflect the changing oxygen requirements of the fetus. The first switch from embryonic ε- to fetal γ-globin occurs at six weeks of gestation. The second switch from γ- to adult δ- and β-globin occurs shortly after birth. Throughout the locus, cis-acting elements exist that are dynamically bound by trans-acting proteins, including transcription factors, co-activators, repressors, and chromatin modifiers. Discovery of novel erythroid-specific transcription factors and a role for chromatin structure in gene expression have enhanced our understanding of the mechanism of globin gene switching. However, the hierarchy of events regulating gene expression during development, from extracellular signaling to transcriptional activation or repression, is complex. In this review we attempt to unify the current knowledge regarding the interplay of cis-acting elements, transcription factors, and chromatin modifiers into a comprehensive overview of globin gene switching.
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Flood, Amar H., Robert J. A. Ramirez, Wei-Qiao Deng, Richard P. Muller, William A. Goddard III, and J. Fraser Stoddart. "Meccano on the Nanoscale—A Blueprint for Making Some of the World's Tiniest Machines." Australian Journal of Chemistry 57, no. 4 (2004): 301. http://dx.doi.org/10.1071/ch03307.
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Molecular compounds—comprised of mechanically interlocked components—such as rotaxanes and catenanes can be designed to display readily controllable internal movements of one component with respect to the other. Since the weak noncovalent bonding interactions that contribute to the template-directed synthesis of such compounds live on between the components thereafter, they can be activated such that the components move in either a linear fashion (rotaxanes) or a rotary manner (catenanes). These molecules can be activated by switching the recognition elements off and on between components chemically, electrically, or optically, such that they perform motions reminiscent of the moving parts in macroscopic machines. This review will highlight how the emergence of the mechanical bond in chemistry during the last two decades has brought with it a real prospect of integrating a bottom-up approach, based on molecular design and micro- and nanofabrication, to construct molecular electronic devices that store information at very high densities using minimal power. Although most of the research reported in this review on switchable catenanes and rotaxanes has been carried out in the context of solution-phase mechanical processes, recent results demonstrate that relative mechanical movements between the components in interlocked molecules can be stimulated (a) chemically in Langmuir and Langmuir–Blodgett films, (b) electrochemically as self-assembled monolayers on gold, and (c) electronically within the settings of solid-state devices. Not only has reversible, electronically driven switching been observed in devices incorporating a bistable [2]catenane, but a crosspoint random access memory circuit has been fabricated using an amphiphilic, bistable [2]rotaxane. The experiments provide strong evidence that switchable catenanes and rotaxanes operate mechanically in a soft-matter environment and can withstand simple device-processing steps. Studies on single-walled carbon nanotubes used as one of the electrodes in molecular switch tunnel junctions have revealed that interfacial chemical interactions involving electrodes containing carbon, silicon, and oxygen are good choices when carrying out molecular electronics on the class of rotaxane- and catenane-based molecules reported in this review. This conclusion is supported by differential conductance measurements (at 4 K) made with single-molecule transistors using the break-junction method. It transpires that the electronic transport properties in such devices are more sensitive to the chemical nature of the molecule–electrode contacts than the details of the molecules' electronic structure away from the contacts. This result has profound implications for molecular electronics and highlights the importance of also considering the molecules and the electrodes as an integrated system. It all adds up to an integrated systems-oriented approach to nanotechnology that finds its inspiration in the transfer of concepts like molecular recognition from the life sciences into materials science and provides a model for how, in principle, to transfer elements of traditional chemistry to technology platforms that are being developed on the nanoscale. Before there can be any serious prospect of a technology, there has to be some good, sound science in the making. Molecular electronics is very much in its infancy and, as such, it can be expected to give rise to a great deal of intellectually stimulating science before it stands half a chance of becoming a viable companion to silicon-based technology.
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DeZazzo, J. D., E. Falck-Pedersen, and M. J. Imperiale. "Sequences regulating temporal poly(A) site switching in the adenovirus major late transcription unit." Molecular and Cellular Biology 11, no. 12 (1991): 5977–84. http://dx.doi.org/10.1128/mcb.11.12.5977-5984.1991.
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Temporal regulation of poly(A) site choice occurs in an adenovirus recombinant encoding a miniature version of the major late transcription unit with two poly(A) sites, L1 and L3. Using deletion mutagenesis, we have looked directly for cis-acting elements regulating poly(A) site choice in this recombinant. From this work, we draw two main conclusions. First, elements other than the AAUAAA and downstream sequences of the L1 poly(A) site are required for temporal regulation of poly(A) site choice during infection. Second, these regions function in two distinct modes during infection. The two regions enhance selection of the L1 poly(A) site in an additive manner during an early infection, but deletion of either element abolishes the switch in poly(A) site choice during a late infection. This work documents the first example of a regulatory element downstream of a core poly(A) region.
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Schwider, J., W. Stork, N. Streibl, and R. Vökel. "Possibilities and limitations of space-variant holographic optical elements for switching networks and general interconnects." Applied Optics 31, no. 35 (1992): 7403. http://dx.doi.org/10.1364/ao.31.007403.
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Rank, Gerhard, Matthias Prestel, and Renato Paro. "Transcription through Intergenic Chromosomal Memory Elements of the Drosophila Bithorax Complex Correlates with an Epigenetic Switch." Molecular and Cellular Biology 22, no. 22 (2002): 8026–34. http://dx.doi.org/10.1128/mcb.22.22.8026-8034.2002.
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ABSTRACT The proteins of the trithorax and Polycomb groups maintain the differential expression pattern of homeotic genes established by the early embryonic patterning system during development. These proteins generate stable and heritable chromatin structures by acting via particular chromosomal memory elements. We established a transgenic assay system showing that the Polycomb group response elements bxd and Mcp confer epigenetic inheritance throughout development. With previously published data for the Fab7 cellular memory module, we confirmed the cellular memory function of Polycomb group response elements. In Drosophila melanogaster, several of these memory elements are located in the large intergenic regulatory regions of the homeotic bithorax complex. Using a transgene assay, we showed that transcription through a memory element correlated with the relief of silencing imposed by the Polycomb group proteins and established an epigenetically heritable active chromatin mode. A memory element remodeled by the process of transcription was able to maintain active expression of a reporter gene throughout development. Thus, transcription appears to reset and change epigenetic marks at chromosomal memory elements regulated by the Polycomb and trithorax proteins. Interestingly, in the bithorax complex of D. melanogaster, the segment-specific expression of noncoding intergenic transcripts during embryogenesis seems to fulfill this switching role for memory elements regulating the homeotic genes.
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Chern, Jyh-Long, and John K. McIver. "Switching types and all-optical flip-flop operations in a ring cavity with four nonlinear elements." Optics Letters 15, no. 3 (1990): 186. http://dx.doi.org/10.1364/ol.15.000186.
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Dabrazhynetskaya, Alena, Therese Brendler, Xinhua Ji, and Stuart Austin. "Switching Protein-DNA Recognition Specificity by Single-Amino-Acid Substitutions in the P1 par Family of Plasmid Partition Elements." Journal of Bacteriology 191, no. 4 (2008): 1126–31. http://dx.doi.org/10.1128/jb.01358-08.
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ABSTRACT The P1, P7, and pMT1 par systems are members of the P1 par family of plasmid partition elements. Each has a ParA ATPase and a ParB protein that recognizes the parS partition site of its own plasmid type to promote the active segregation of the plasmid DNA to daughter cells. ParB contacts two parS motifs known as BoxA and BoxB, the latter of which determines species specificity. We found that the substitution of a single orthologous amino acid in ParB for that of a different species has major effects on the specificity of recognition. A single change in ParB can cause a complete switch in recognition specificity to that of another species or can abolish specificity. Specificity changes do not necessarily correlate with changes in the gross DNA binding properties of the protein. Molecular modeling suggests that species specificity is determined by the capacity to form a hydrogen bond between ParB residue 288 and the second base in the BoxB sequence. As changes in just one ParB residue and one BoxB base can alter species specificity, plasmids may use such simple changes to evolve new species rapidly.
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Wilmes-Riesenberg, M. R., and B. L. Wanner. "TnphoA and TnphoA' elements for making and switching fusions for study of transcription, translation, and cell surface localization." Journal of Bacteriology 174, no. 14 (1992): 4558–75. http://dx.doi.org/10.1128/jb.174.14.4558-4575.1992.
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Kozak, Maciej, Artur Bejger, and Arkadiusz Tomczak. "Identification of Gate Turn-Off Thyristor Switching Patterns Using Acoustic Emission Sensors." Sensors 21, no. 1 (2020): 70. http://dx.doi.org/10.3390/s21010070.
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Modern seagoing ships are often equipped with converters which utilize semiconductor power electronics devices like thyristors or power transistors. Most of them are used in driving applications such as powerful main propulsion plants, auxiliary podded drives and thrusters. When it comes to main propulsion drives the power gets seriously high, thus the need for use of medium voltage power electronics devices arises. As it turns out, power electronic parts are the most susceptible to faults or failures in the whole electric drive system. These devices require efficient cooling, so manufacturers design housings in a way that best dissipates heat from the inside of the chips to the metal housing. This results in susceptibility to damage due to the heterogeneity of combined materials and the difference in temperature expansion of elements inside the power device. Currently used methods of prediction of damage and wear of semiconductor elements are limited to measurements of electrical quantities generated by devices during operation and not quite effective in case of early-stage damage to semiconductor layers. The article presents an introduction and preliminary tests of a method utilizing an acoustic emission sensor which can be used in detecting early stage damages of the gate turn-off thyristor. Theoretical considerations and chosen experimental results of initial measurements of acoustic emission signals of the medium voltage gate turn-off thyristor are presented.
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Sohlberg, Karl, Hongjun Gao, and Stephen J. Penny cook. "Mechanism of Reversible Conductance Transitions in a Crystalline Thin-Film." Microscopy and Microanalysis 6, S2 (2000): 146–47. http://dx.doi.org/10.1017/s1431927600033225.
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Recently there has been considerable interest in developing nanometer- and sub-nanometer-scale electronic devices. Of particular interest in this regard is whether individual molecules or molecular complexes can be employed as electronic device elements. Aviram et al. have reported switching and rectification in an organic thin film. More recently, Potember et al. have shown a field-induced conductance transition on a 500 nm scale, but did not demonstrate local reversibility of the transition. The reverse transition was induced only by application of a broad laser pulse or heat. We have observed and replicated reversible conductance transitions in a fully-organic crystalline complex, on a scale close to the dimensions of the unit cell.A crystalline thin-film organic complex of 3-nitrobenzal malononitrile and 1,4-phenylenediamine (NBMN-pDA), exhibits reversible conductance transitions on the sub-nanometer scale when exposed to local electric field pulses from an STM tip.
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Navas, Patrick A., Yongqi Yan, Minerva E. Sanchez, Ericka M. Johnson, and George Stamatoyannopoulos. "Talen-Mediated Knock Outs Of Cis and Trans Elements Potentially Involved In Globin Gene Switching." Blood 122, no. 21 (2013): 436. http://dx.doi.org/10.1182/blood.v122.21.436.436.
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Abstract Transcription activator-like effector nucleases (TALEN) are engineered proteins used for precise genome editing by generating specific DNA double strand that are repaired by homologous recombination and by non-homologous end joining. TALENs can be used to study gene regulation by deleting putative regulatory elements in the context of the native chromosome and measuring mRNA synthesis. We designed TALENs to delete individual DNAse I-hypersensitive sites (HS) of the β-globin locus control region (LCR) followed by an assessment of globin gene expression and assessment of epigenetic effects in K562 erythroleukemia cells. The β-globin LCR is composed of five HSs and functions as a powerful regulatory element responsible for appropriate levels of the five β-like globin genes during development. Introduction of plasmid DNA encoding a pair of TALENs and targeting individually the flanking region of the HS2, HS3 and HS4 core elements along with a donor 100 base single-stranded oligonucleotide resulted in the successful deletions of each of the three core elements in K562 cells. Individual K562 cells were seeded to produce clones and the mutations were screened by PCR to identify both heterozygous and homozygous clones. The TALEN-mediated 288 bp HS2 core deletion resulted 32 heterozygous (48.5%) and 6 homozygous clones (9.1%) in a total of 66 clones screened. K562 carries three copies of chromosome 11 emphasizing the robustness of TALEN technology to target each of the alleles. In the 199 bp HS3 core deletion, from 113 clones we identified 28 heterozygous (24.8%) and 3 (2.7%) homozygous clones. Lastly, the 301 bp HS4 core deletion yielded 9 homozygous (5.9%) and 12 heterozygous (7.9%) clones from 151 clones screened. Total RNA was isolated from wild-type K562 cells, and from both the heterozygous and homozygous mutant clones and subjected to RNase Protection analysis to quantitate the levels of globin mRNA. Deletion if the HS3 core in K562 cells in a ∼30% reduction in ε-globin mRNA and 2-fold reduction in γ-globin mRNA. A more dramatic effect on globin expression is observed in the HS2 core deletion, as ε- and γ-globin expression is reduced by 2- and 5-fold, respectively. These results suggest that HS2 contributes the majority of the LCR enhancer function in K562 cells. The HS4 core deletion resulted in a modest ∼20% reduction in both ε- and γ-globin expression. TALENs were designed to knockout trans-acting factors implicated to be involved in globin gene regulation and/or globin switching. TALENs bracketing the gene promoters and the first exon of 25 genes encoding either a transcription factor or histone-modifying enzyme were synthesized and post-transfection PCR screens of the transfected pool of K562 cells resulted in the successful identification of 17 gene knockouts. The 17 target genes are PRMT5, LDB1, EIF2AK3, BCL11A, HBSIL, MYB, SOX6, NFE4, NR2F2, NR2C1, NR2C2, CHTOP, NFE2, DNMT3A, RBBP4, MTA2 and MBD2. Single cell clones have been generated by limited dilution of transfected K562 pools and thus far we have identified heterozygous and homozygous clones of 8 of 17 gene knockouts, importantly all clones were identified without selection. The frequency of identifying the knockout clones, represented by the number of clones screened/ number of heterozygous clones/ number of homozygous clones, are as follows: HBS1L (63/3/0), SOX6 (68/13/2), NFE4 (56/13/7), LBD1 (300/2/0), MBD2 (301/0/1), CHTOP (288/66/6), NFE2 (712/44/5) and NR2C1 (96/40/11). The remaining nine gene knockouts and globin gene expression data will be presented at the meetings. These studies highlight a powerful TALEN-mutagenesis platform for target deletions of both cis- and trans-elements to study globin gene switching. TALENs can be synthesized in several days and the screening of the individual clones for the desired knockouts is completed within two weeks. This highly efficient mutagenesis platform will further our understanding of the molecular basis of globin switching. Disclosures: No relevant conflicts of interest to declare.
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Sabatino, Denise E., Amanda P. Cline, Patrick G. Gallagher та ін. "Substitution of the Human β-Spectrin Promoter for the Human Aγ-Globin Promoter Prevents Silencing of a Linked Human β-Globin Gene in Transgenic Mice". Molecular and Cellular Biology 18, № 11 (1998): 6634–40. http://dx.doi.org/10.1128/mcb.18.11.6634.
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ABSTRACT During development, changes occur in both the sites of erythropoiesis and the globin genes expressed at each developmental stage. Previous work has shown that high-level expression of human β-like globin genes in transgenic mice requires the presence of the locus control region (LCR). Models of hemoglobin switching propose that the LCR and/or stage-specific elements interact with globin gene sequences to activate specific genes in erythroid cells. To test these models, we generated transgenic mice which contain the human Aγ-globin gene linked to a 576-bp fragment containing the human β-spectrin promoter. In these mice, the β-spectrin Aγ-globin (βsp/Aγ) transgene was expressed at high levels in erythroid cells throughout development. Transgenic mice containing a 40-kb cosmid construct with the micro-LCR, βsp/Aγ-, ψβ-, δ-, and β-globin genes showed no developmental switching and expressed both human γ- and β-globin mRNAs in erythroid cells throughout development. Mice containing control cosmids with the Aγ-globin gene promoter showed developmental switching and expressed Aγ-globin mRNA in yolk sac and fetal liver erythroid cells and β-globin mRNA in fetal liver and adult erythroid cells. Our results suggest that replacement of the γ-globin promoter with the β-spectrin promoter allows the expression of the β-globin gene. We conclude that the γ-globin promoter is necessary and sufficient to suppress the expression of the β-globin gene in yolk sac erythroid cells.
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Герасимов, I. Gerasimov, Яшин, and A. Yashin. "Ion-Molecular Memory Model. Memory Structure, its Bandwidth, the Switches and the Controllers of Information." Journal of New Medical Technologies 21, no. 3 (2014): 191–95. http://dx.doi.org/10.12737/5933.
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This paper discusses the memory structure in its basic characteristics: bandwidth, switching and &#34;dispatching&#34; of information flows in the system memory organization. Bandwidth is associated with the filtering of information flows; in the radiophysics analogy – as &#34;signal -noise&#34;. Selection of information should be made according to its energy content. For completeness and detail of the developed model of memory, the authors introduced the concept of switches and memory controllers, as the molecular, cellular and other compounds that distribute (send) useful information in the appropriate sections of the library of memory. All elements memory can evolve as structuring, filling and restructuring of library memory. Within the developed by the authors of ion-molecular memory model the real work to the greatest extent uses radio physical analogy as a universal approach in all scientific fields, where the paramount consideration are the objects of information processing. It has become a scientific axiom; the main thing is that a certain (radio)physical formalism in specific model was found as the adequacy of the studied processes. The authors have paid special attention to these issues, including in a strict sequence and hierarchy of the presented material. It was especially emphasized that the evolution of all and classifying bandwidth of the memory elements subject to overall systemic laws structuring and optimization (radio)physical interpretation.
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Chan, Fung-Yee, Judith Robinson, Alison Brownlie та ін. "Characterization of Adult α- and β-Globin Genes in the Zebrafish". Blood 89, № 2 (1997): 688–700. http://dx.doi.org/10.1182/blood.v89.2.688.
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Abstract Developmental switching of hemoglobins (Hbs) occurs in most vertebrates, yet the cellular and molecular basis for this process remains elusive. The zebrafish is a new genetic and developmental system that can be used to study embryogenesis, and mutants with a variety of defects in hematopoiesis have recently been derived. To initiate our studies on Hb switching in this organism, we have characterized the globins expressed in the adult. Reversed-phase high performance liquid chromatography and mass spectrometric analyses of adult peripheral blood hemolysates showed that there are three major α globins and two β globins in circulating erythroid cells. In addition, we have isolated and characterized zebrafish adult α- and β-globin cDNA clones that encode some of these globins. High levels of α- and β-globin gene expression were detected in adult erythroid cells, whereas embryonic erythroid cells expressed little, if any, of these RNAs. We have also shown that the α- and β-globin genes are tightly linked on the same chromosome and are arrayed in a 3′-5′ to 5′-3′ configuration, respectively. The characterization of these genes and regulatory elements in this globin locus will provide insight into the process of globin gene transcription. With these reagents, future studies of Hb switching in zebrafish mutants with defective hematopoiesis will be possible.
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Gazouli, Maria, Elena Katsantoni, Theodore Kosteas та Nicholas P. Anagnou. "Persistent Human γ-Globin Expression in Adult Transgenic Mice Following Selective Deletion of Two Repressor Elements Located 3′ to the Aγ-Globin Gene." Blood 108, № 11 (2006): 1585. http://dx.doi.org/10.1182/blood.v108.11.1585.1585.
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Abstract Adult β-globin gene expression is tightly regulated during development and hematopoiesis. The human globin genes undergoing two developmental switches are regulated by a complex interplay between cis-acting elements and stage-specific trans-acting factors. Understanding the molecular basis of globin gene switching is of particular interest as persistent expression of the fetal γ-globin genes in the adult ameliorates the effects of hemoglobinopathies. Natural occurring deletions within the human β-globin gene cluster lead to specific clinical syndromes characterized by increased production of fetal hemoglobin (HbF) in adult life. These clinical syndromes provide an excellent model to reveal and delineate novel cis-acting elements involved in the developmental control of hemoglobin switching. One major hypothesis, which accounts for these distinct phenotypic features, assumes that silencers located within the Aγ to δ gene region, are deleted in both HPFH and δβ-thalassemias leading to the failure of switching. Previous studies of our laboratory suggested that four elements (Enh, F, O and P) located within the Aγ toδ globin intergenic region, exhibited silencer activity in transient assays (Clin Res 41:308, 1993 and Blood 84:506, 1994) and that the Enh and F elements were capable of down-regulating transcription of the human β-globin locus in an embryonic-specific manner in transgenic mice (Exp Hematol 32:224, 2004). In the present study, we sought to further clarify the in vivo role of the Enh and F elements in the silencing of the fetal Aγ-gene. To this end, we have generated transgenic mice by using cosmid constructs containing the full length human globin LCR linked to the 3.3 kb Aγ gene, lacking both the Enh and F elements. As controls, we used transgenic lines containing the full length LCR linked to the 5.6 kb Aγ-gene construct, which includes both the Enh and F elements, previously shown by us (Blood102:3412, 2003) and others (Nature350:252, 1991) to be autonomously regulated during the perinatal period. Three transgenic lines for the LCR 3.3 kb Aγ-gene construct have been generated. Cosmid integrity and copy numbers (2, 3 and 4 copies respectively) were determined by Southern blot analysis. Expression analysis in adult blood RNA performed by S1 nuclease protection and real-time reverse transcriptase PCR, documented persistence of expression of Aγ-gene in adult life. To further investigate whether the persistence of Aγ-gene expression was not a non-specific effect of the multicopy integrants, we generated a new series of single copy mice by cross-breeding the three transgenic lines with a line expressing the Cre recombinase gene (CAG-Cre). As expected, in the control LCR-5.6 kb Aγ lines, containing the Enh and F elements, the Aγ-globin gene was silenced in all lines tested in the adult stage. In contrast, high levels of Aγ-globin gene expression, similar to those of multicopy integrants were documented in all three generated single copy LCR-3.3 kb Aγ lines, lacking the Enh and F elements. Thus, this study documents directly for the first time the in vivo role of of these two gene-proximal negative regulatory elements on the silencing of the Aγ-gene in the perinatal period and may permit the design of future therapeutic strategies for their exploitation in therapeutic approaches for thalassemias.
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Kiechle, Markus, Anna A. Friedl, Palaniyandi Manivasakam, Friederike Eckardt-Schupp, and Robert H. Schiestl. "DNA Integration by Ty Integrase in yku70Mutant Saccharomyces cerevisiae Cells." Molecular and Cellular Biology 20, no. 23 (2000): 8836–44. http://dx.doi.org/10.1128/mcb.20.23.8836-8844.2000.
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ABSTRACT In the present work we examined nonhomologous integration of plasmid DNA in a yku70 mutant. Ten of 14 plasmids integrated as composite elements, including Ty sequences probably originating from erroneous strand-switching and/or priming events. Three additional plasmids integrated via Ty integrase without cointegrating Ty sequences, as inferred from 5-bp target site duplication and integration site preferences. Ty integrase-mediated integration of non-Ty DNA has never been observed in wild-type cells, although purified integrase is capable of using non-Ty DNA as a substrate in vitro. Hence our data implicate yKu70 as the cellular function preventing integrase from accepting non-Ty DNA as a substrate.
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Golovin, Andrii. "Smectic-A-filled birefringent elements and fast switching twisted dual-frequency nematic cells used for digital light deflection." Optical Engineering 45, no. 4 (2006): 044002. http://dx.doi.org/10.1117/1.2192520.
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Kim, Hyun Suk, Joon Seok Park, Tae Sang Kim, et al. "Defect Control in Zinc Oxynitride Semiconductor for High-Performance and High-Stability Thin-Film Transistors." Solid State Phenomena 205-206 (October 2013): 446–50. http://dx.doi.org/10.4028/www.scientific.net/ssp.205-206.446.
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The fabrication of thin-film transistor devices incorporating active semiconductors based on zinc oxynitride (ZnON) compound is presented. It is demonstrated that the addition of appropriate dopant, gallium, in ZnON, suppresses the formation of shallow donor, nitrogen vacancies, and significantly improves electrical characteristics of the resulting TFT. The Ga:ZnON devices with field-effect mobility values exceeding 50 cm2/Vs are achieved, which makes them suitable as switching or driving elements in next-generation flat-panel displays.
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Genov, Nikolai, Alireza Basti, Mónica Abreu, and Angela Relógio. "Temporal Splicing Switches in Elements of the TNF-Pathway Identified by Computational Analysis of Transcriptome Data for Human Cell Lines." International Journal of Molecular Sciences 20, no. 5 (2019): 1182. http://dx.doi.org/10.3390/ijms20051182.
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Alternative splicing plays an important role in numerous cellular processes and aberrant splice decisions are associated with cancer. Although some studies point to a regulation of alternative splicing and its effector mechanisms in a time-dependent manner, the extent and consequences of such a regulation remains poorly understood. In the present work, we investigated the time-dependent production of isoforms in two Hodgkin lymphoma cell lines of different progression stages (HD-MY-Z, stage IIIb and L-1236, stage IV) compared to a B lymphoblastoid cell line (LCL-HO) with a focus on tumour necrosis factor (TNF) pathway-related elements. For this, we used newly generated time-course RNA-sequencing data from the mentioned cell lines and applied a computational pipeline to identify genes with isoform-switching behaviour in time. We analysed the temporal profiles of the identified events and evaluated in detail the potential functional implications of alterations in isoform expression for the selected top-switching genes. Our data indicate that elements within the TNF pathway undergo a time-dependent variation in isoform production with a putative impact on cell migration, proliferation and apoptosis. These include the genes TRAF1, TNFRSF12A and NFKB2. Our results point to a role of temporal alternative splicing in isoform production, which may alter the outcome of the TNF pathway and impact on tumorigenesis.
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Mazur, Krzysztof, Jaroslaw Rzepecki, Anna Pietruszewska, Stanislaw Wrona, and Marek Pawelczyk. "Vibroacoustical Performance Analysis of a Rigid Device Casing with Piezoelectric Shunt Damping." Sensors 21, no. 7 (2021): 2517. http://dx.doi.org/10.3390/s21072517.
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Noise and vibration are common issues that may have a negative impact on human’s’ health. To minimize their consequences, several vibroacoustical methods may be employed. One well-known method is Piezoelectric Shunt Damping (PSD). Over the years, many approaches have been investigated, from passive, state switching circuits to active pulse-switching. In this paper, the authors propose three PSD implementations—passive Synchronized Switch Damping on Inductor (SSDI), semi-active SSDI and active Synchronized Switch Damping on Voltage source (SSDV)—for a single-panel structure mounted on a rigid-frame casing. The nine Macro Fiber Composite (MFC) elements were mounted on the plate based on preliminary simulations in FreeFEM. Then, the theoretical results were validated by an identification experiment. The main research is concentrated on the Sound Pressure Level (SPL) and structural vibrations reduction for selected frequencies. The active method provided the highest reduction of vibration—up to 5.5 dB for maximal possible loudspeaker level without overdrive and up to 7.5 dB for lower excitation levels.
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Shin, Eunjung, Qianying Ye, and Sung-Jae Lee. "Active Transposition of Insertion Sequences in Prokaryotes: Insights from the Response of Deinococcus geothermalis to Oxidative Stress." Antioxidants 11, no. 3 (2022): 481. http://dx.doi.org/10.3390/antiox11030481.
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Bacterial genomes contain numerous insertion sequences (ISs) as transposable elements involved in actions such as the sequestration, transmission, mutation and activation of genes that can influence the responsive capacity of the organism to environmental challenges. To date, at least 30 IS families have been identified. In this review, we describe how certain ISs are transposed to carotenoid biosynthesis genes, such as phytoene synthase and phytoene desaturase, when radiation-resistant Deinococcus geothermalis with a redox imbalance and a targeted gene disruption mutation is exposed to oxidative stressors, such as gamma-irradiation, dielectric bilayer discharge plasma and hydrogen peroxide. We also explain the genetic features of IS elements, spontaneous mutation and various stress responses, including nutrient limitation, and physicochemical and oxidative stress, associated with the active transposition of bacterial ISs. Based on the current knowledge, we posit that the redox signalling mechanism inducing IS transposition involves redox sensing and redox switching for the activation of transposase expression and its activity.
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Ramírez Arroyave, Germán Augusto, Antoni Barlabé, Lluís Pradell, Javier Leonardo Araque Quijano, Bedri A. Cetiner, and Luis Jofre-Roca. "Design of Minimum Nonlinear Distortion Reconfigurable Antennas for Next-Generation Communication Systems." Sensors 21, no. 7 (2021): 2557. http://dx.doi.org/10.3390/s21072557.
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Nonlinear effects in the radio front-end can degrade communication quality and system performance. In this paper we present a new design technique for reconfigurable antennas that minimizes the nonlinear distortion and maximizes power efficiency through the minimization of the coupling between the internal switching ports and the external feeding ports. As a nonlinear design and validation instance, we present the nonlinear characterization up to 50 GHz of a PIN diode commonly used as a switch for reconfigurable devices in the microwave band. Nonlinear models are extracted through X-parameter measurements supported by accurate calibration and de-embedding procedures. Nonlinear switch models are validated by S-parameter measurements in the low power signal regime and by harmonic measurements in the large-signal regime and are further used to predict the measured nonlinearities of a reconfigurable antenna. These models have the desired particularity of being integrated straightforwardly in the internal multi-port method formulation, which is used and extended to account for the power induced on the switching elements. A new figure of merit for the design of reconfigurable antennas is introduced—the power margin, that is, the power difference between the fed port and the switching elements, which combined with the nonlinear load models directly translates into nonlinearities and power-efficiency-related metrics. Therefore, beyond traditional antenna aspects such as port match, gain, and beam orientation, switch power criteria are included in the design methodology. Guidelines for the design of reconfigurable antennas and parasitic layers of minimum nonlinearity are provided as well as the inherent trade-offs. A particular antenna design suitable for 5G communications in the 3.5 GHz band is presented according to these guidelines, in which the specific switching states for a set of target performance metrics are obtained via a balancing of the available figures of merit with multi-objective separation criteria, which enables good control of the various design trade-offs. Average Error Vector Magnitude (EVM) and power efficiency improvement of 12 and 6 dB, respectively, are obtained with the application of this design approach. In summary, this paper introduces a new framework for the nonlinear modeling and design of reconfigurable antennas and provides a set of general-purpose tools applicable in cases beyond those used as examples and validation in this work. Additionally, the use of these models and guidelines is presented, demonstrating one of the most appealing advantages of the reconfigurable parasitic layer approach, their low nonlinearity.
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Lee, Bum-Soo, Shiv I. S. Grewal, and Amar J. S. Klar. "Biochemical Interactions between Proteins and mat1 cis-Acting Sequences Required for Imprinting in Fission Yeast." Molecular and Cellular Biology 24, no. 22 (2004): 9813–22. http://dx.doi.org/10.1128/mcb.24.22.9813-9822.2004.
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ABSTRACT DNA recombination required for mating type (mat1) switching in Schizosaccharomyces pombe is initiated by mat1 imprinting. The imprinting event is regulated by mat1 cis-acting elements and by several trans-acting factors, including swi1 (for switch), swi3, swi7, and sap1. swi1 and swi3 were previously shown to function in dictating unidirectional mat1 DNA replication by controlling replication fork movement around the mat1 region and, second, by pausing fork progression around the imprint site. With biochemical studies, we investigated whether the trans-acting factors function indirectly or directly by binding to the mat1 cis-acting sequences. First, we report the identification and DNA sequence of the swi3 gene. swi3 is not essential for viability, and, like the other factors, it exerts a stimulatory effect on imprinting. Second, we showed that only Swi1p and Swi3p interact to form a multiprotein complex and that complex formation did not require their binding to a DNA region defined by the smt-0 mutation. Third, we found that the Swi1p-Swi3p complex physically binds to a region around the imprint site where pausing of replication occurs. Fourth, the protein complex also interacted with the mat1-proximal polar terminator of replication (RTS1). These results suggest that the stimulatory effect of swi1 and swi3 on switching and imprinting occurs through interaction of the Swi1p-Swi3p complex with the mat1 regions.
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DIAZ, A., J. H. PARK, and I. C. KHOO. "DESIGN AND TRANSMISSION-REFLECTION PROPERTIES OF LIQUID CRYSTALLINE OPTICAL METAMATERIALS WITH LARGE BIREFRINGENCE AND SUB-UNITY OR NEGATIVE-REFRACTIVE INDEX." Journal of Nonlinear Optical Physics & Materials 16, no. 04 (2007): 533–49. http://dx.doi.org/10.1142/s0218863507003883.
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The dispersion of nanoparticles in a nematic liquid crystal host medium provides an efficient way of designing tunable optical metamaterials that respond from the visible to the Terahertz and microwave regime. As studied in this article, these systems exhibit much larger birefringence than the nematic host and possess sub-unity, zero, and even negative refractive indices with unique reflection and transmission properties. These tunable optical metamaterials will enable a wide range of application possibilities in next-generation reflective, transmissive, modulation and switching elements and devices.
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Elizar’ev, P. V., D. V. Lomaev, D. A. Chetverina, P. G. Georgiev, and M. M. Erokhin. "Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster." Acta Naturae 8, no. 2 (2016): 79–86. http://dx.doi.org/10.32607/20758251-2016-8-2-79-86.
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Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.
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Kim, Taehoon, Fabian Fool, Djalma Simoes dos Santos, et al. "Design of an Ultrasound Transceiver ASIC with a Switching-Artifact Reduction Technique for 3D Carotid Artery Imaging." Sensors 21, no. 1 (2020): 150. http://dx.doi.org/10.3390/s21010150.
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This paper presents an ultrasound transceiver application-specific integrated circuit (ASIC) directly integrated with an array of 12 × 80 piezoelectric transducer elements to enable next-generation ultrasound probes for 3D carotid artery imaging. The ASIC, implemented in a 0.18 µm high-voltage Bipolar-CMOS-DMOS (HV BCD) process, adopted a programmable switch matrix that allowed selected transducer elements in each row to be connected to a transmit and receive channel of an imaging system. This made the probe operate like an electronically translatable linear array, allowing large-aperture matrix arrays to be interfaced with a manageable number of system channels. This paper presents a second-generation ASIC that employed an improved switch design to minimize clock feedthrough and charge-injection effects of high-voltage metal–oxide–semiconductor field-effect transistors (HV MOSFETs), which in the first-generation ASIC caused parasitic transmissions and associated imaging artifacts. The proposed switch controller, implemented with cascaded non-overlapping clock generators, generated control signals with improved timing to mitigate the effects of these non-idealities. Both simulation results and electrical measurements showed a 20 dB reduction of the switching artifacts. In addition, an acoustic pulse-echo measurement successfully demonstrated a 20 dB reduction of imaging artifacts.
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Harris, Miera B., Chih-Chao Chang, Michael T. Berton та ін. "Transcriptional Repression of Stat6-Dependent Interleukin-4-Induced Genes by BCL-6: Specific Regulation of Iɛ Transcription and Immunoglobulin E Switching". Molecular and Cellular Biology 19, № 10 (1999): 7264–75. http://dx.doi.org/10.1128/mcb.19.10.7264.
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ABSTRACT The BCL-6 proto-oncogene encodes a POZ/zinc-finger transcription factor that is expressed in B cells and a subset of CD4+ T cells within germinal centers. Recent evidence suggests that BCL-6 can act as a sequence-specific repressor of transcription, but the target genes for this activity have not yet been identified. The binding site for BCL-6 shares striking homology to the sites that are the target sequence for the interleukin-4 (IL-4)-induced Stat6 (signal transducers and activators of transcription) signaling molecule. Electrophoretic mobility shift assays demonstrate that BCL-6 can bind, with different affinities, to several DNA elements recognized by Stat6. Expression of BCL-6 can repress the IL-4-dependent induction of immunoglobulin (Ig) germ line ɛ transcripts, but does not repress the IL-4 induction of CD23 transcripts. Consistent with the role of BCL-6 in modulating transcription from the germ line ɛ promoter, BCL-6−/−mice display an increased ability to class switch to IgE in response to IL-4 in vitro. These animals also exhibit a multiorgan inflammatory disease characterized by the presence of a large number of IgE+ B cells. The apparent dysregulation of IgE production is abolished in BCL-6−/− Stat6−/− mice, indicating that BCL-6 regulation of Ig class switching is dependent upon Stat6 signaling. Thus, BCL-6 can modulate the transcription of selective Stat6-dependent IL-4 responses, including IgE class switching in B cells.
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Olivier, Catherine, Guillaume Poirier, Patrick Gendron, Anita Boisgontier, François Major, and Pascal Chartrand. "Identification of a Conserved RNA Motif Essential for She2p Recognition and mRNA Localization to the Yeast Bud." Molecular and Cellular Biology 25, no. 11 (2005): 4752–66. http://dx.doi.org/10.1128/mcb.25.11.4752-4766.2005.
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ABSTRACT In Saccharomyces cerevisiae, over twenty mRNAs localize to the bud tip of daughter cells, playing roles in processes as different as mating type switching and plasma membrane targeting. The localization of these transcripts depends on interactions between a cis-acting localization element(s) or zipcodes and the RNA-binding protein She2p. While previous studies identified four different localization elements in the bud-localized ASH1 mRNA, the main determinants for She2p recognition are still unknown. To investigate the RNA-binding specificity of She2p, we isolated She2p-binding RNAs by in vivo selection from libraries of partially randomized ASH1 localization elements. The RNAs isolated contained a similar loop-stem-loop structure with a highly conserved CGA triplet in one loop and a single conserved cytosine in the other loop. Mutating these conserved nucleotides or the stem separating them resulted in the loss of She2p binding and in the delocalization of a reporter mRNA. Using this information, we identified the same RNA motif in two other known bud-localized transcripts, suggesting that this motif is conserved among bud-localized mRNAs. These results show that mRNAs with zipcodes lacking primary sequence similarity can rely on a few conserved nucleotides properly oriented in their three-dimensional structure in order to be recognized by the same localization machinery.
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Chastanet, Arnaud, and Richard Losick. "Just-in-Time Control of Spo0A Synthesis in Bacillus subtilis by Multiple Regulatory Mechanisms." Journal of Bacteriology 193, no. 22 (2011): 6366–74. http://dx.doi.org/10.1128/jb.06057-11.
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The response regulator Spo0A governs multiple developmental processes inBacillus subtilis, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription ofspo0Ais governed by a promoter switching mechanism, involving a vegetative, σA-recognized promoter, Pv, and a sporulation σH-recognized promoter, Ps, that is under phosphorylated Spo0A (Spo0A∼P) control. Thespo0Aregulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O1, O2, O3, and O4in reverse order of their proximity to the coding sequence. Here we report that O1is responsible for repressing Pvduring the transition to stationary phase, that O2is responsible for repressing Psduring growth, that O3is responsible for activating Psat the start of sporulation, and that O4is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from Pvis impeded due to RNA secondary structure whereas mRNAs originating from Psare fully competent for protein synthesis. We propose that the opposing actions of O2and O3and the enhanced translatability of mRNAs originating from Pscreate a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.
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Wang, Wei, Li-Jun Chen, Xu-Qing Wang, et al. "Organometallic rotaxane dendrimers with fourth-generation mechanically interlocked branches." Proceedings of the National Academy of Sciences 112, no. 18 (2015): 5597–601. http://dx.doi.org/10.1073/pnas.1500489112.
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Mechanically interlocked molecules, such as catenanes, rotaxanes, and knots, have applications in information storage, switching devices, and chemical catalysis. Rotaxanes are dumbbell-shaped molecules that are threaded through a large ring, and the relative motion of the two components along each other can respond to external stimuli. Multiple rotaxane units can amplify responsiveness, and repetitively branched molecules—dendrimers—can serve as vehicles for assembly of many rotaxanes on single, monodisperse compounds. Here, we report the synthesis of higher-generation rotaxane dendrimers by a divergent approach. Linkages were introduced as spacer elements to reduce crowding and to facilitate rotaxane motion, even at the congested periphery of the compounds up to the fourth generation. The structures were characterized by 1D multinuclear (1H, 13C, and 31P) and 2D NMR spectroscopy, MALDI-TOF-MS, gel permeation chromatography (GPC), and microscopy-based methods including atomic force microscopy (AFM) and transmission electron microscopy (TEM). AFM and TEM studies of rotaxane dendrimers vs. model dendrimers show that the rotaxane units enhance the rigidity and reduce the tendency of these assemblies to collapse by self-folding. Surface functionalization of the dendrimers with ferrocenes as termini produced electrochemically active assemblies. The preparation of dendrimers with a well-defined topological structure, enhanced rigidity, and diverse functional groups opens previously unidentified avenues for the application of these materials in molecular electronics and materials science.
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Russell, J. Eric, Julia Morales, Aleksandr V. Makeyev та Stephen A. Liebhaber. "Sequence Divergence in the 3′ Untranslated Regions of Human ζ- and α-Globin mRNAs Mediates a Difference in Their Stabilities and Contributes to Efficient α-to-ζ Gene Developmental Switching". Molecular and Cellular Biology 18, № 4 (1998): 2173–83. http://dx.doi.org/10.1128/mcb.18.4.2173.
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ABSTRACT The developmental stage-specific expression of human globin proteins is characterized by a switch from the coexpression of ζ- and α-globin in the embryonic yolk sac to exclusive expression of α-globin during fetal and adult life. Recent studies with transgenic mice demonstrate that in addition to transcriptional control elements, full developmental silencing of the human ζ-globin gene requires elements encoded within the transcribed region. In the current work, we establish that these latter elements operate posttranscriptionally by reducing the relative stability of ζ-globin mRNA. Using a transgenic mouse model system, we demonstrate that human ζ-globin mRNA is unstable in adult erythroid cells relative to the highly stable human α-globin mRNA. A critical determinant of the difference between α- and ζ-globin mRNA stability is mapped by in vivo expression studies to their respective 3′ untranslated regions (3′UTRs). In vitro messenger ribonucleoprotein (mRNP) assembly assays demonstrate that the α- and ζ-globin 3′UTRs assemble a previously described mRNP stability-determining complex, the α-complex, with distinctly different affinities. The diminished efficiency of α-complex assembly on the ζ 3′UTR results from a single C→G nucleotide substitution in a crucial polypyrimidine tract contained by both the human α- and ζ-globin mRNA 3′UTRs. A potential pathway for accelerated ζ-globin mRNA decay is suggested by the observation that its 3′UTR encodes a shortened poly(A) tail. Based upon these data, we propose a model for ζ-globin gene silencing in fetal and adult erythroid cells in which posttranscriptional controls play a central role by providing for accelerated clearance of ζ-globin transcripts.
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Çakır, M. Volkan, Hans Binder, and Henry Wirth. "Profiling of Genetic Switches using Boolean Implications in Expression Data." Journal of Integrative Bioinformatics 11, no. 1 (2014): 30–54. http://dx.doi.org/10.1515/jib-2014-246.
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Summary Correlation analysis assuming coexpression of the genes is a widely used method for gene expression analysis in molecular biology. Yet growing extent, quality and dimensionality of the molecular biological data permits emerging, more sophisticated approaches like Boolean implications. We present an approach which is a combination of the SOM (self organizing maps) machine learning method and Boolean implication analysis to identify relations between genes, metagenes and similarly behaving metagene groups (spots). Our method provides a way to assign Boolean states to genes/metagenes/spots and offers a functional view over significantly variant elements of gene expression data on these three different levels. While being able to cover relations between weakly correlated entities Boolean implication method also decomposes these relations into six implication classes. Our method allows one to validate or identify potential relationships between genes and functional modules of interest and to assess their switching behaviour. Furthermore the output of the method renders it possible to construct and study the network of genes. By providing logical implications as updating rules for the network it can also serve to aid modelling approaches.
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Luche, R. M., W. C. Smart, T. Marion, M. Tillman, R. A. Sumrada, and T. G. Cooper. "Saccharomyces cerevisiae BUF protein binds to sequences participating in DNA replication in addition to those mediating transcriptional repression (URS1) and activation." Molecular and Cellular Biology 13, no. 9 (1993): 5749–61. http://dx.doi.org/10.1128/mcb.13.9.5749-5761.1993.
Full textAbstract:
The heteromeric BUF protein was originally shown to bind to URS1 elements which are situated upstream of many genes in Saccharomyces cerevisiae and mediate negative control of their transcription. Among the genes regulated through the URS1 site and the proteins interacting with it are those participating in carbon, nitrogen, and inositol metabolism; electron transport; meiosis; sporulation; and mating-type switching. We show here that pure BUF protein, in addition to binding to the negatively acting URS1 site, also binds to CAR1 sequences supporting transcriptional activation (upstream activation sequences). To determine the BUF protein structure, we cloned and sequenced the BUF1 and BUF2 genes and found them to be identical to the RF-A (RP-A) gene whose products participate in yeast DNA replication as single-stranded DNA binding proteins. These data argue that BUF protein-binding sites serve multiple roles in transcription and replication.
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Gumucio, D. L., H. Heilstedt-Williamson, T. A. Gray, et al. "Phylogenetic footprinting reveals a nuclear protein which binds to silencer sequences in the human gamma and epsilon globin genes." Molecular and Cellular Biology 12, no. 11 (1992): 4919–29. http://dx.doi.org/10.1128/mcb.12.11.4919-4929.1992.
Full textAbstract:
Tissue- and developmental stage-specific expression of the human beta-like globin genes is regulated by a combination of ubiquitous and erythroid-restricted trans factors that bind to cis elements near each of the five active genes. Additional interactions of these cis and trans factors with sequences located in the far 5' end of the cluster occur by as yet obscure mechanisms. Because of the complexity of this regulatory puzzle, precise identification of the determinants that control hemoglobin switching has proven difficult. Phylogenetic footprinting is an evolutionary approach to this problem which is based on the supposition that the basic mechanisms of switching are conserved throughout mammalian phylogeny. Alignment of the 5' flanking regions of the gamma genes of several species allows the identification of footprints of 100% conserved sequence. We have now tested oligomers spanning 13 such phylogenetic footprints and find that 12 are bound by nuclear proteins. One conserved element located at -1086 from the gamma genes exhibits repressor activity in transient transfection studies. The protein that binds this element, CSBP-1 (conserved sequence-binding protein 1), also binds at three sites within a silencer element upstream from the epsilon globin gene. Further analysis reveals that the CSBP-1 binding activity is identical to that of a recently cloned zinc finger protein that has been shown to act as a repressor in other systems. The binding of CSPB-1 to silencer sequences in the epsilon and gamma globin genes may be important in the stage-specific silencing of these genes.