Abstract
Acoustic silencers are the most effective solution to control noise in ducts. In this paper, we propose a compact acoustic meta-silencer (AMS) based on the synergy between reactive and ...resistive units that enables the reduction of low-frequency and broadband noise. We first propose a conceptual AMS comprising simple reactive and resistive units to verify its unique sound attenuation performance. To explore its potential for application, we then propose an advanced AMS unit consisting of two independent annular chambers that represent reactive and resistive units, respectively. The synergistic mechanism between reactive and resistive units to achieve superior sound attenuation is revealed. Next, the band structures of the infinite periodic advanced AMS are discussed, and three different types of advanced AMS containing six units are examined. It is demonstrated numerically and experimentally that the optimized AMS with a compact size can achieve a transmission loss higher than 15 dB over a super-wide low-frequency range (290–1344 Hz). The work here provides a new avenue for the design of low-frequency and broadband meta-silencers to control the noise in ducts.
Abstract Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective ...deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases. Epigenetic mechanisms involve chromatin remodeling by relatively generic complexes that catalyze DNA methylation and various types of histone modifications. There is increasing evidence that these complexes are directed to their sites of action by long non-protein-coding RNAs (lncRNAs), of which there are tens if not hundreds of thousands specified in the genome. LncRNAs are transcribed in complex intergenic, overlapping and antisense patterns relative to adjacent protein-coding genes, suggesting that many lncRNAs regulate the expression of these genes. LncRNAs also participate in a wide array of subcellular processes, including the formation and function of cellular organelles. Most lncRNAs are transcribed in a developmentally regulated and cell type specific manner, particularly in the CNS, wherein over half of all lncRNAs are expressed. While the numerous biological functions of lncRNAs are yet to be characterized fully, a number of recent studies suggest that lnRNAs are important for mediating cell identity. This function seems to be especially important for generating the enormous array of regional neuronal and glial cell subtypes that are present in the CNS. Further studies have also begun to elucidate additional roles played by lncRNAs in CNS processes, including homeostasis, stress responses and plasticity. Herein, we review emerging evidence that highlights the expression and function of lncRNAs in the CNS and suggests that lncRNA deregulation is an important factor in various CNS pathologies including neurodevelopmental, neurodegenerative and neuroimmunological disorders, primary brain tumors, and psychiatric diseases.
•A programmable resonator called shunted electromechanical resonator (SEMR) is proposed and theoretical analyzed, which is proved in experiments•The resonance frequency, ideally, can be programed in ...the frequency range of (0 ∞) as long as the resistance of the pre-design shunt circuits approaching zero•The programing process of the mechanical resonance only requires coding the supplied DC voltages to the MOSFET switches•The frequency range of tuning is much broader than existing technology
As the most classical device, Helmholtz resonator (HR) is simple and robust leading its widely using in control of sound wave. However, it performs only in the vicinity of its resonant frequency which restrains its application scope. Method to extending its effective frequency range is long-time sought by various techniques. This study introduces a programmable resonator whose resonance frequency is determined by a programed voltage states. In this resonator, the mass inducing neck is replaced by the diaphragm of a moving-coil loudspeaker which is shunted by an analog circuit. The acoustic impedance of the diaphragm, hence the resonance frequency, is dominated by the circuit through the electromechanical coupling induced by a moving-coil in a DC magnetic field. To program the resonance, a multiple branches programmable circuit is designed. The connecting state of each branch of circuit is coded by a low-voltage supplied to a metal-oxide-semiconductor field-effect transistor (MOSFET) switch cascading the branch. By programming the voltages, the resonance frequency is successfully coded. Both down-tuning and up-tuning of the resonance frequency is realized in impedance tube experiment which agrees well with the lumped parameter model developed in this work. The tuning range is up to 1 octave in experiments and infinite large in theory if superconducting coil is used.
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Expression vectors (EVs) are artificial nucleic acid molecules with a modular structure that allows for the transcription of DNA sequences of interest in either cellular or cell-free environments. ...These vectors have emerged as cross-disciplinary tools with multiple applications in an expanding Life Sciences market. The cis-regulatory sequences (CRSs) that control the transcription in EVs are typically sourced from either viruses or from characterized genes. However, the recent advancement in transposable elements (TEs) technology provides attractive alternatives that may enable a significant improvement in the design of EVs. Commonly known as "jumping genes," due to their ability to move between genetic loci, TEs are constitutive components of both eukaryotic and prokaryotic genomes. TEs harbor native CRSs that allow the regulated transcription of transposition-related genes. However, some TE-related CRSs display striking characteristics, which provides the opportunity to reconsider TEs as lead actors in the design of EVs. In this article, we provide a synopsis of the transcriptional control elements commonly found in EVs together with an extensive discussion of their advantages and limitations. We also highlight the latest findings that may allow for the implementation of TE-derived sequences in the EVs feasible, possibly improving existing vectors. By introducing this new concept of TEs as a source of regulatory sequences, we aim to stimulate a profitable discussion of the potential advantages and benefits of developing a new generation of EVs based on the use of TE-derived control sequences.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
ThPOK is a “master regulator” of T lymphocyte lineage choice, whose presence or absence is sufficient to dictate development to the CD4 or CD8 lineages, respectively. Induction of ThPOK is ...transcriptionally regulated, via a lineage-specific silencer element, SilThPOK. Here, we take advantage of the available genome sequence data as well as site-specific gene targeting technology, to evaluate the functional conservation of ThPOK regulation across mammalian evolution, and assess the importance of motif grammar (order and orientation of TF binding sites) on SilThPOK function in vivo. We make three important points: First, the SilThPOK is present in marsupial and placental mammals, but is not found in available genome assemblies of nonmammalian vertebrates, indicating that it arose after divergence of mammals from other vertebrates. Secondly, by replacing the murine SilThPOK in situ with its marsupial equivalent using a knockin approach, we demonstrate that the marsupial SilThPOK supports correct CD4 T lymphocyte lineage-specification in mice. To our knowledge, this is the first in vivo demonstration of functional equivalency for a silencer element between marsupial and placental mammals using a definitive knockin approach. Finally, we show that alteration of the position/orientation of a highly conserved region within the murine SilThPOK is sufficient to destroy silencer activity in vivo, demonstrating that motif grammar of this “solid” synteny block is critical for silencer function. Dependence of SilThPOK function on motif grammar conserved since the mid-Jurassic age, 165 Ma, suggests that the SilThPOK operates as a silenceosome, by analogy with the previously proposed enhanceosome model.
Alternative splicing of pre-mRNAs is a major contributor to both proteomic diversity and control of gene expression levels. Splicing is tightly regulated in different tissues and developmental ...stages, and its disruption can lead to a wide range of human diseases. An important long-term goal in the splicing field is to determine a set of rules or "code" for splicing that will enable prediction of the splicing pattern of any primary transcript from its sequence. Outside of the core splice site motifs, the bulk of the information required for splicing is thought to be contained in exonic and intronic cis-regulatory elements that function by recruitment of sequence-specific RNA-binding protein factors that either activate or repress the use of adjacent splice sites. Here, we summarize the current state of knowledge of splicing cis-regulatory elements and their context-dependent effects on splicing, emphasizing recent global/genome-wide studies and open questions.
Objective To systemically characterize the genome-wide distribution of H3K27me3-marked silencers in gastric intestinal metaplasia (IM) tissues and to elucidate a novel epigenetic regulatory mechanism ...of IM. Methods Gastric antrum mucosa samples were collected from 22 healthy individuals and 39 patients with IM. The modification of H3K27me3 and the transcriptome characteristics were detected by Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing and RNA sequencing, respectively. Various bioinformatics tools, such as Ngsplot, ChIPseeker, MAnorm2, GGBiPlot, edgeR, Homer and others were applied for analyzing the silencer signal and its regulation on gene expression of IM tissues. Results CUT&Tag sequencing and RNA sequencing data were of great quality, and there was no significance in the whole-genome distribution of H3K27me3 modification between normal gastric mucosa and IM tissues. Genome-scale distribution of H3K27me3-marked silencers was also portrayed, which revealed weakened silencer signal intensi
The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is ...widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.
Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes, among other genes. We investigated the transcriptional regulation of Aicda ...(which encodes AID) in class switch-inducible CH12F3-2 cells and found that Aicda regulation involved derepression by several layers of positive regulatory elements in addition to the 5' promoter region. The 5' upstream region contained functional motifs for the response to signaling by cytokines, the ligand for the costimulatory molecule CD40 or stimuli that activated the transcription factor NF-kappaB. The first intron contained functional binding elements for the ubiquitous silencers c-Myb and E2f and for the B cell-specific activator Pax5 and E-box-binding proteins. Our results show that Aicda is regulated by the balance between B cell-specific and stimulation-responsive elements and ubiquitous silencers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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