•Domain wall motion is controlled by radial orientation of the transverse field.•Results are explained in terms of the transverse anisotropy in the cross-section.•The effect can be used for direct ...domain wall manipulation.
Ferromagnetic domain wall with transverse configuration is a source of local magnetic fields that strongly interacts with external fields. In this paper, we show that domain wall dynamics can be effectively tailored by the application of a transverse magnetic field of a certain direction. Depending on the direction of the transverse field, the domain wall velocity is either higher or lower. Our measurements carried out by the Sixtus-Tonks experiment show that a certain direction of the transverse magnetic field could completely block the domain wall propagation. The effect is explained by a distribution of transverse magnetic anisotropy induced into the cylindrical wire during its production.
Sterile alpha motif and histidine‐aspartic acid domain‐containing protein 1 (SAMHD1), a dNTP triphosphohydrolase, regulates the levels of cellular dNTPs through their hydrolysis. SAMHD1 protects ...cells from invading viruses that depend on dNTPs to replicate and is frequently mutated in cancers and Aicardi–Goutières syndrome, a hereditary autoimmune encephalopathy. We discovered that SAMHD1 localizes at the immunoglobulin (Ig) switch region, and serves as a novel DNA repair regulator of Ig class switch recombination (CSR). Depletion of SAMHD1 impaired not only CSR but also IgH/c‐Myc translocation. Consistently, we could inhibit these two processes by elevating the cellular nucleotide pool. A high frequency of nucleotide insertion at the break‐point junctions is a notable feature in SAMHD1 deficiency during activation‐induced cytidine deaminase‐mediated genomic instability. Interestingly, CSR induced by staggered but not blunt, double‐stranded DNA breaks was impaired by SAMHD1 depletion, which was accompanied by enhanced nucleotide insertions at recombination junctions. We propose that SAMHD1‐mediated dNTP balance regulates dNTP‐sensitive DNA end‐processing enzyme and promotes CSR and aberrant genomic rearrangements by suppressing the insertional DNA repair pathway.
Synopsis
Sterile alpha motif and histidine‐aspartic acid domain‐containing protein 1 (SAMHD1) is a dNTP triphosphohydrolase (dNTPase) that protects cells from viral infection and is frequently mutated in cancers and Aicardi‐Goutières syndrome. Here, we demonstrate that depletion of nucleotide by SAMHD1 promotes activation induced cytidine deaminase (AID)‐dependent antibody class switch recombination (CSR) and genomic instability in B cells.
SAMHD1 associates with immunoglobulin switch regions, and promotes CSR and aberrant IgH/c‐Myc translocations.
The dNTPase activity of SAMHD1 but not its interaction with CtIP is required for efficient CSR.
The depletion of SAMHD1 impairs end‐joining of AID‐ or Cas9 nickase‐induced staggered DSBs.
Accumulation of dNTPs upon SAMHD1 depletion likely modulates the activities of dNTP‐sensitive end‐repair enzymes which interfere with the normal ligation program and leads to end‐joining by pathways that lead to nucleotide insertions.
Localization of the HIV‐1 restriction factor SAMHD1 to the immunoglobulin switch region on chromosomes regulates AID‐dependent class‐switch recombination and genomic stability in B‐lymphocytes.
Time-frequency analysis can reveal local variations and allow for separation of phase and amplitude information of nonstationary seismic waveforms. Seismic signals are used since long as a robust ...tool for inversion of underground structures, as has been the practice in geophysical exploration. However, the mixing of phase and amplitude in seismic data increases the nonlinearity of seismic inversion. The authors first use Gabor transform to separate the phase and amplitude information of envelope data, and then introduce an adaptive factor into the misfit function to redistribute the weight of phase and amplitude information for direct envelope inversion (DEI) in the time-frequency domain. By adopting this procedure, greater flexibility can be achieved in operating the local phase of envelope and waveform spectra to enhance stability of multiscale phase inversion. For DEI, the direct envelope Fréchet derivative is used, and thus, no weak scattering assumption is imposed on the joint multiscale DEI of phase and amplitude (PADEI). Compared with the DEI method, the PADEI can better recover the deeper parts of salt-bottom and subsalt structures by boosting the signal energy and weakening the nonlinearity of the waveform inversion.
Metamaterials present the possibility of artificially generating advanced functionalities through engineering of their internal structure. Artificial spin networks, in which a large number of ...nanoscale magnetic elements are coupled together, are promising metamaterial candidates that enable the control of collective magnetic behavior through tuning of the local interaction between elements. In this work, the motion of magnetic domain‐walls in an artificial spin network leads to a tunable stochastic response of the metamaterial, which can be tailored through an external magnetic field and local lattice modifications. This type of tunable stochastic network produces a controllable random response exploiting intrinsic stochasticity within magnetic domain‐wall motion at the nanoscale. An iconic demonstration used to illustrate the control of randomness is the Galton board. In this system, multiple balls fall into an array of pegs to generate a bell‐shaped curve that can be modified via the array spacing or the tilt of the board. A nanoscale recreation of this experiment using an artificial spin network is employed to demonstrate tunable stochasticity. This type of tunable stochastic network opens new paths toward post‐Von Neumann computing architectures such as Bayesian sensing or random neural networks, in which stochasticity is harnessed to efficiently perform complex computational tasks.
The motion of magnetic domain‐walls within artificial spin networks leads to a tunable stochastic response of the metamaterial, which can be tailored through an external field and local lattice modifications. This type of tunable stochastic network can produce a controllable random response, as demonstrated by recreating a nanoscale version of the Galton board, the iconic experiment historically used to showcase the emergence of order from chaos.
This paper investigates the regularity, non-impulsiveness, stability and admissibility of the singular fractional-order systems with the fractional-order <inline-formula> <tex-math ...notation="LaTeX">\alpha \in (0,1) </tex-math></inline-formula>. Firstly, the structure, existence and uniqueness of the time domain solutions of singular fractional-order systems are analyzed based on the Kronecker equivalent standard form. The necessary and sufficient condition for the regularity of singular fractional-order systems is proposed on the basis of the above analysis. Secondly, the necessary and sufficient conditions of non-impulsiveness as well as stability are obtained based on the proposed time domain solutions of singular fractional-order systems, respectively. Thirdly, two novel sufficient and necessary conditions for the admissibility of singular fractional-order systems are derived including the non-strict linear matrix inequality form and the linear matrix inequality form with equality constraints. Finally, two numerical examples are given to show the effectiveness of the proposed results.
Potassium channels participate in many biological functions, from ion homeostasis to generation and modulation of the electrical membrane potential. They are involved in a large variety of diseases. ...In the human genome, 15 genes code for K+ channels with two pore domains (K2P). These channels form dimers of pore‐forming subunits that produce background conductances finely regulated by a range of natural and chemical effectors, including signalling lipids, temperature, pressure, pH, antidepressants and volatile anaesthetics. Since the cloning of TWIK1, the prototypical member of this family, a lot of work has been carried out on their structure and biology. These studies are still in progress, but data gathered so far show that K2P channels are central players in many processes, including ion homeostasis, hormone secretion, cell development and excitability. A growing number of studies underline their implication in physiopathological mechanisms, such as vascular and pulmonary hypertension, cardiac arrhythmias, nociception, neuroprotection and depression. This review gives a synthetic view of the most noticeable features of these channels.
In this article, an electromagnetic-thermal coupling algorithm based on the discontinuous Galerkin time-domain (DGTD) and spectral-element time-domain (SETD) methods is proposed, which can adopt two ...independent grids for thermal simulation and electrical simulation, respectively. It employs time-domain solvers for both the electrical and thermal fields. Compared with the conventional cosimulation scheme (e.g., time-domain solvers for the thermal field and frequency-domain solver for the electrical field), it can provide better simulation precision for problems characterized with small size or drastic field changes. By comparing the results of electromagnetic-thermal coupling simulation with the results of electromagnetic simulation, the effect of temperature change on electromagnetic field propagation is analyzed.
Breast cancer is the second leading cause of cancer‑associated mortality among women worldwide. Triple‑negative breast cancer (TNBC) accounts for 15‑20% of all breast cancers and is defined by its ...aggressive nature and limited treatment options. Therefore, there is an urgent need to develop effective therapies for TNBC in order to improve breast cancer outcomes, as targeted therapies have done in other subtypes of breast cancer. Discoidin domain receptor tyrosine kinase 1 (DDR1) is activated by collagens, which are important components of the tumor stroma; therefore, DDR1 may serve a critical role in the communication between tumor cells and the tumor microenvironment. The aim of the present study was to determine how tumor DDR1 regulated tumor growth by affecting tumor infiltrated T cells. First, the DDR1 expression levels from a cohort of patients with breast cancer were analyzed. The results revealed that there were higher levels of DDR1 expression in tumor tissues compared with adjacent normal tissues. Overexpression of DDR1 in 4T1 cells promoted tumor growth in vivo, while knockout of DDR1 in EMT6 cells decreased tumor growth in vivo. In addition, it was revealed that DDR1 regulated tumor growth by modulating tumor infiltrating T cells, CD4+ and CD8+. Furthermore, inhibition of DDR1 by neutralizing antibodies decreased breast cancer growth in vivo. To the best of our knowledge, the results of the present study demonstrated for the first time that DDR1 expressed on the tumor cells promoted breast tumor growth by suppressing antitumor immunity. The present findings indicated that DDR1 may not only have a critical role in the progression of breast cancer, but may also serve as a potential therapeutic target for breast cancer, particularly TNBC.
Animal toxins that modulate the activity of voltage-gated sodium (Na
) channels are broadly divided into two categories-pore blockers and gating modifiers. The pore blockers tetrodotoxin (TTX) and ...saxitoxin (STX) are responsible for puffer fish and shellfish poisoning in humans, respectively. Here, we present structures of the insect Na
channel Na
PaS bound to a gating modifier toxin Dc1a at 2.8 angstrom-resolution and in the presence of TTX or STX at 2.6-Å and 3.2-Å resolution, respectively. Dc1a inserts into the cleft between VSD
and the pore of Na
PaS, making key contacts with both domains. The structures with bound TTX or STX reveal the molecular details for the specific blockade of Na
access to the selectivity filter from the extracellular side by these guanidinium toxins. The structures shed light on structure-based development of Na
channel drugs.
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