Non-Abelian inverse Anderson transitions

Inverse Anderson transitions, where the flat-band localization is destroyed by disorder, have been wildly investigated in quantum and classical systems in the presence of Abelian gauge fields. Here, we report the first investigation on inverse Anderson transitions in the system with non-Abelian gauge fields. It is found that pseudospin-dependent localized and delocalized eigenstates coexist in the disordered non-Abelian Aharonov-Bohm cage, making inverse Anderson transitions depend on the relative phase of two internal pseudospins. Such an exotic phenomenon induced by the interplay between non-Abelian gauge fields and disorder has no Abelian analogy. Furthermore, we theoretically design and experimentally fabricate nonAbelian Aharonov-Bohm topolectrical circuits to observe the non-Abelian inverse Anderson transition. Through the direct measurements of frequency-dependent impedance responses and voltage dynamics, the pseudospin-dependent non-Abelian inverse Anderson transitions are observed. Our results establish the connection between inverse Anderson transitions and non-Abelian gauge fields, and thus comprise a new insight on the fundamental aspects of localization in disordered non-Abelian flat-band systems

Observation of inverse Anderson transitions in Aharonov-Bohm topolectrical circuits

It is well known that Anderson transition is a disorder-induced metal-insulator transition.Contrary to this conventional wisdom, some investigations have shown that disorders could destroy the phase coherence of localized modes in flatbands, making the localized states melt into extended states. This phenomenon is called the inverse Anderson transition. While, to date, the experimental observation of inverse Anderson transitions is still lacking. In this work, we report the implementation of inverse Anderson transitions based on Aharonov-Bohm topolectrical circuits. Different types of disorders, including symmetric-correlated, antisymmetric-correlated and uncorrelated disorders, can be easily implemented in Aharonov-Bohm circuits by engineering the spatial distribution of ground settings. Through the direct measurements of frequency-dependent impedance responses and time-domain voltage dynamics, the inverse Anderson transitions induced by antisymmetric-correlated disorders are clearly observed. Moreover, the flat bands and associated spatial localizations are also fulfilled in clean Aharonov-Bohm circuits or Aharonov-Bohm circuits sustaining symmetric-correlated and uncorrelated disorders, respectively. Our proposal provides a flexible platform to investigate the interplay between the geometric localization and Anderson localization, and could have potential applications in electronic signal control.Comment: 12 pages, 4 figure

Web Service Reputation Evaluation Based on QoS Measurement

In the early service transactions, quality of service (QoS) information was published by service provider which was not always true and credible. For better verification the trust of the QoS information was provided by the Web service. In this paper, the factual QoS running data are collected by our WS-QoS measurement tool; based on these objectivity data, an algorithm compares the difference of the offered and measured quality data of the service and gives the similarity, and then a reputation evaluation method computes the reputation level of the Web service based on the similarity. The initial implementation and experiment with three Web services' example show that this approach is feasible and these values can act as the references for subsequent consumers to select the service

Aurora B Regulates Formin mDia3 in Achieving Metaphase Chromosome Alignment

SummaryProper bipolar attachment of sister kinetochores to the mitotic spindle is critical for accurate chromosome segregation in mitosis. Here we show an essential role of the formin mDia3 in achieving metaphase chromosome alignment. This function is independent of mDia3 actin nucleation activity, but is attributable to EB1-binding by mDia3. Furthermore, the microtubule binding FH2 domain of mDia3 is phosphorylated by Aurora B kinase in vitro, and cells expressing the nonphosphorylatable mDia3 mutant cannot position chromosomes at the metaphase plate. Purified recombinant mDia3 phosphorylated by Aurora B exhibits reduced ability to bind microtubules and stabilize microtubules against cold-induced disassembly in vitro. Cells expressing the phosphomimetic mDia3 mutant do not form stable kinetochore microtubule fibers; despite they are able to congress chromosomes to the metaphase plate. These findings reveal a key role for mDia3 and its regulation by Aurora B phosphorylation in achieving proper stable kinetochore microtubule attachment

Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers

Potent immunosuppressive mechanisms within the tumor microenvironment contribute to the resistance of aggressive human cancers to immune checkpoint blockade (ICB) therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs) to induce T cell tolerance is through secretion of reactive nitrogen species (RNS), which nitrates tyrosine residues in proteins involved in T cell function. However, so far very few nitrated proteins have been identified. Here, using a transgenic mouse model of prostate cancer and a syngeneic cell line model of lung cancer, we applied a nitroproteomic approach based on chemical derivation of 3-nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is nitrated at Tyr394 by MDSCs. LCK nitration inhibits T cell activation, leading to reduced interleukin 2 (IL2) production and proliferation. In human T cells with defective endogenous LCK, wild type, but not nitrated LCK, rescues IL2 production. In the mouse model of castration-resistant prostate cancer (CRPC) by prostate-specific deletion of Pten, p53, and Smad4, CRPC is resistant to an ICB therapy composed of antiprogrammed cell death 1 (PD1) and anticytotoxic-T lymphocyte-associated protein 4 (CTLA4) antibodies. However, we showed that ICB elicits strong anti-CRPC efficacy when combined with an RNS neutralizing agent. Together, these data identify a previously unknown mechanism of T cell inactivation by MDSC-induced protein nitration and illuminate a clinical path hypothesis for combining ICB with RNS-reducing agents in the treatment of CRPC

Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing

RBM15, an RNA binding protein, determines cell-fate specification of many tissues including blood. We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578 leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). Overexpression of PRMT1 in acute megakaryocytic leukemia cell lines blocks megakaryocyte terminal differentiation by downregulation of RBM15 protein level. Restoring RBM15 protein level rescues megakaryocyte terminal differentiation blocked by PRMT1 overexpression. At the molecular level, RBM15 binds to pre-mRNA intronic regions of genes important for megakaryopoiesis such as GATA1, RUNX1, TAL1 and c-MPL. Furthermore, preferential binding of RBM15 to specific intronic regions recruits the splicing factor SF3B1 to the same sites for alternative splicing. Therefore, PRMT1 regulates alternative RNA splicing via reducing RBM15 protein concentration. Targeting PRMT1 may be a curative therapy to restore megakaryocyte differentiation for acute megakaryocytic leukemia

Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk