The integral equation (IE) method is commonly utilized to model time-harmonic electromagnetic (EM) problems. One of the greatest challenges in its applications arises in the solution of the resulting ...ill-conditioned matrix equation. We introduce a new domain decomposition method (DDM) for the IE solution of EM wave scattering from non-penetrable objects. The proposed method is a non-overlapping/non-conformal DDM and it provides a computationally efficient and effective preconditioner for the IE matrix equations. Moreover, the proposed approach is very suitable for dealing with multi-scale electromagnetic problems since each sub-domain has its own characteristics length and will be meshed independently. Furthermore, for each sub-domain, we are free to choose the most effective IE sub-domain solver based on its local geometrical features and electromagnetic characteristics. Additionally, the multilevel fast multi-pole algorithm (MLFMA) is utilized to accelerate the computations of couplings between sub-domains. Numerical results demonstrate that the proposed method yields rapid convergence in the outer Krylov iterative solution process. Finally, simulations of several large-scale examples testify to the effectiveness and robustness of the proposed IE based DDM.
A
bstract
A supersymmetric Pati-Salam model with wrapping number equal to 5 has been constructed in Type IIA orientifolds on
T
6
/
(
ℤ
2
× ℤ
2
) with intersecting D6-branes recently. In particular, ...the string-scale gauge coupling unification can be achieved due to the intermediate-scale vector-like particles from
N
= 2 sector. We calculate the supersymmetry breaking soft terms, and study the Standard Model (SM) fermion masses and mixings. There are nine pairs of Higgs doublets from
N
= 2 sector. Interestingly, we can explain the SM quark masses and mixings, as well as the charged leptons masses from three point and four-point Yukawa interactions. Moreover, we calculate the supersymmetry breaking soft terms in a previous model with gauge coupling unification since we find a typo in the previous study.
Significance Intracellular accumulation of the abnormally modified tau is hallmark pathology of AD, but the mechanism leading to tau aggregation is not fully characterized. In the present study, we ...studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, degradation, and aggregation. We discovered that sumoylation competes with ubiquitination in modifying tau, correlating with tau hyperphosphorylation. Identification of the posttranslational modification on tau provides the new insight into the molecular mechanism in tau aggregation.
Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer’s disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and β-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation.
Overexpressing Tau counteracts apoptosis and increases dephosphorylated β‐catenin levels, but the underlying mechanisms are elusive. Here, we show that Tau can directly and robustly acetylate ...β‐catenin at K49 in a concentration‐, time‐, and pH‐dependent manner. β‐catenin K49 acetylation inhibits its phosphorylation and its ubiquitination‐associated proteolysis, thus increasing β‐catenin protein levels. K49 acetylation further promotes nuclear translocation and the transcriptional activity of β‐catenin, and increases the expression of survival‐promoting genes (bcl2 and survivin), counteracting apoptosis. Mutation of Tau's acetyltransferase domain or co‐expressing non‐acetylatable β‐catenin‐K49R prevents increased β‐catenin signaling and abolishes the anti‐apoptotic function of Tau. Our data reveal that Tau preserves β‐catenin by acetylating K49, and upregulated β‐catenin/survival signaling in turn mediates the anti‐apoptotic effect of Tau.
Synopsis
Tau acetylates β‐catenin at K49, which stabilizes β‐catenin by inhibiting its phosphorylation and ubiquitination‐associated proteolysis. β‐catenin mediates the anti‐apoptotic effects of Tau by increasing the expression of survival‐promoting genes.
Tau can acetylate β‐catenin at K49 in a concentration‐, time‐ pH‐ and acetyltransferase domain‐dependent manner.
K49‐acetylation by Tau preserves β‐catenin by inhibiting its phosphorylation and ubiquitination‐associated proteolysis, resulting in increased nuclear translocation and enhanced transcriptional activity of β‐catenin.
β‐catenin K49‐acetylation mediates the anti‐apoptotic effects of Tau by augmenting the expression of survival‐promoting genes.
Tau acetylates β‐catenin at K49, which stabilizes β‐catenin by inhibiting its phosphorylation and ubiquitination‐associated proteolysis. β‐catenin mediates the anti‐apoptotic effects of Tau by increasing the expression of survival‐promoting genes.
Ca3SnSi2‐xGexO9 (0 ≤ x ≤ 0.8) and (1–y) Ca3SnSi1.6Ge0.4O9 – y CaSnSiO5 – 2 wt% LiF (y = 0.4 and 0.5) microwave dielectric ceramics were prepared by traditional solid‐state reaction through sintering ...at 1250°C–1425°C for 5 h and at 875°C for 2 h, respectively. Ge4+ replaced Si4+, and Ca3SnSi2‐xGexO9 (0 ≤ x ≤ 0.4) solid solutions were obtained. At 0.1 ≤ x ≤ 0.4, the Ge4+ substitution for Si4+ decreased the sintering temperature of Ca3SnSi2‐xGexO9 from 1425 to 1300°C, the SnO6 octahedral distortions, and the average CaO7 decahedral distortions, which affected the τf value. The large average decahedral distortions corresponded with nearer‐zero τf values at Ca3SnSi2‐xGexO9 (0.1 ≤ x ≤ 0.4) ceramics. The τf value and sintering temperature of Ca3SnSi2‐xGexO9 (x = 0.4) ceramic were adjusted to near‐zero by CaSnSiO5 and decreased to 875°C upon the addition of 2 wt% LiF. The (1 – y) Ca3SnSi1.6Ge0.4O9 – y CaSnSiO5 – 2 wt% LiF (y = 0.5) ceramic sintered at 875°C for 2 h exhibited good microwave dielectric properties: εr = 10.3, Q × f = 14 300 GHz (at 12.2 GHz), and τf = ‒5.8 ppm/°C.
We designed and synthesized a new tripyridine dipyrrolide pincer ligand, which could be doubly deprotonated to provide five-nitrogen-donor sites and then utilized to prepare a subnanometric chiral ...silver cluster. The cluster belongs to an
S
4
point group and shows a double-stranded helicate. DFT calculations were performed to analyze the electronic structure of the cluster. Interestingly, through hierarchical intercluster interactions, the cluster helicates evolve into complex secondary structures including a right-handed helix and a folded sheet, both of which are reminiscent of secondary structures of proteins,
i.e.
, an α-helix and an antiparallel β-sheet.
We report a subnanometric chiral silver cluster double-stranded helicate covered by new NNNNN-type pincer ligands and its hierarchical self-assemblies toward mimicking secondary structures of proteins.
A cross-slot-coupled dual-band circularly polarized rectangular dielectric resonator antenna (RDRA) with a small frequency ratio (1.23) based on compass navigation satellite system (CNSS) ...applications is designed, fabricated, and measured. The RDRA is excited to resonate at two pairs of near-degenerate orthogonal modes of TE111 and TE113, and a cross slot is introduced to simultaneously achieve dual-band right-hand circular polarization. The measured -10 dB impedance bandwidths of 11.4% and 8.4%, 3-dB axial ratio (AR) bandwidths of 2.1% and 2.2%, and antenna gains of over 5.4 and 4.3 dBic are obtained for CNSS B3 and B1 bands, respectively. Reasonable consistency is achieved between measured and simulated results of reflection coefficients, ARs, and radiation patterns.
Ca1+2xSnSi2x+yO3+6x+2y (0.1 ≤ x ≤ 0.9; 0.1 ≤ y ≤ 0.9) microwave dielectric ceramics were prepared through traditional solid‐state reaction sintered at 1450°C–1500°C for 5 hours. The Ca3SnSi2O9 second ...phase replaced the SnO2 second phase of the Ca1+2xSnSi2xO3+6x (x = 0, y = 0) ceramics by controlling the ratio of Ca:Sn:Si. The cracks of CaSnO3 (x = 0, y = 0) ceramic were inhibited, the microwave dielectric properties were optimized by introducing the Ca3SnSi2O9 second phase, and the CaSnO3‐Ca3SnSi2O9 mixture system existed at (0.1 ≤ x ≤ 0.9, y = 0). The CaSnSiO5 phase with positive τf value was related to the Si‐rich in CaSnSiyO3+2y (x = 0; 0.1 ≤ y ≤ 0.9), and the coexistence of three and four phases was obtained at CaSnSiyO3+2y (0.1 ≤ y ≤ 0.9) ceramics. The CaSnSiO5 phase appeared at CaSnSiyO3+2y (0.3 ≤ y ≤ 0.9) ceramics. The CaSnSiyO3+2y (y = 0.8) ceramic with 49.2 wt% CaSnSiO5 phase exhibited excellent microwave dielectric properties: εr = 11.06, Q × f = 57,500 GHz (at 11.5 GHz), and τf = +8.1 ppm/°C.
Protein phosphatase 2A (PP2A) inhibition causes hyperphosphorylation of tau and APP in Alzheimer’s disease (AD). However, the mechanisms underlying the downregulation of PP2A activity in AD brain ...remain unclear. We demonstrate that Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is overexpressed in AD brain. CIP2A-mediated PP2A inhibition drives tau/APP hyperphosphorylation and increases APP β-cleavage and Aβ production. Increase in CIP2A expression also leads to tau mislocalization to dendrites and spines and synaptic degeneration. In mice, injection of AAV-CIP2A to hippocampus induced AD-like cognitive deficits and impairments in long-term potentiation (LTP) and exacerbated AD pathologies in neurons. Indicative of disease exacerbating the feedback loop, we found that increased CIP2A expression and PP2A inhibition in AD brains result from increased Aβ production. In summary, we show that CIP2A overexpression causes PP2A inhibition and AD-related cellular pathology and cognitive deficits, pointing to CIP2A as a potential target for AD therapy.
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•PP2A inhibitor CIP2A is increased in AD human brains•CIP2A promotes β-cleavage of APP and Aβ production through APP-T668 phosphorylation•CIP2A induces tau hyperphosphorylation and mislocalization into dendritic spines•CIP2A causes LTP impairment, synaptic degeneration, and memory deficits in mice
PP2A inactivation plays a key role in AD pathogenesis. Shentu et al. report that endogenous PP2A inhibitor CIP2A is upregulated in AD brains. CIP2A overexpression promotes β-cleavage of APP and tau hyperphosphorylation through PP2A inhibition, leading to impairments in synapse, hippocampal LTP, and memory.
Major depressive disorder (MDD) is a severe mental illness. Decreased brain plasticity and dendritic fields have been consistently found in MDD patients and animal models; however, the underlying ...molecular mechanisms remain to be clarified. Here, we demonstrate that the deletion of cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor of protein phosphatase 2A (PP2A), leads to depression‐like behaviors in mice. Hippocampal RNA sequencing analysis of CIP2A knockout mice shows alterations in the PI3K‐AKT pathway and central nervous system development. In primary neurons, CIP2A stimulates AKT activity and promotes dendritic development. Further analysis reveals that the effect of CIP2A in promoting dendritic development is dependent on PP2A‐AKT signaling. In vivo, CIP2A deficiency‐induced depression‐like behaviors and impaired dendritic arborization are rescued by AKT activation. Decreased CIP2A expression and impaired dendrite branching are observed in a mouse model of chronic unpredictable mild stress (CUMS). Indicative of clinical relevance to humans, CIP2A expression is found decreased in transcriptomes from MDD patients. In conclusion, we discover a novel mechanism that CIP2A deficiency promotes depression through the regulation of PP2A‐AKT signaling and dendritic arborization.
Synopsis
Mice deficient for the PP2A inhibitor CIP2A show reduced dendritic arborization and develop depression‐like behaviors, which can be rescued by AKT activation.
CIP2A deletion induces depression‐like behaviors in mice.
CIP2A promotes dendritic arborization and development through activating AKT.
PP2A mediates the effects of CIP2A on AKT activation and dendritic development.
CIP2A deficiency‐induced depression‐like behaviors and dendrite/spine loss are rescued by AKT activation in mice.
CIP2A deficiency and impaired dendritic arborization coexist in brains of rat models of chronic mild stress‐induced depression.
Mice deficient for the PP2A inhibitor CIP2A show reduced dendritic arborization and develop depression‐like behaviors, which can be rescued by AKT activation.
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