Exceptional Points in a Non-Hermitian Topological Pump

We investigate the effects of non-Hermiticity on topological pumping, and uncover a connection between a topological edge invariant based on topological pumping and the winding numbers of exceptional points. In Hermitian lattices, it is known that the topologically nontrivial regime of the topological pump only arises in the infinite-system limit. In finite non-Hermitian lattices, however, topologically nontrivial behavior can also appear. We show that this can be understood in terms of the effects of encircling a pair of exceptional points during a pumping cycle. This phenomenon is observed experimentally, in a non-Hermitian microwave network containing variable gain amplifiers.Comment: 7 pages, 7 figures. The first author did the experiment, and the second author did the theoretical stud

Measurement of a topological edge invariant in a microwave network

We report on the measurement of topological invariants in an electromagnetic topological insulator analog formed by a microwave network, consisting of the winding numbers of scattering matrix eigenvalues. The experiment can be regarded as a variant of a topological pump, with non-zero winding implying the existence of topological edge states. In microwave networks, unlike most other systems exhibiting topological insulator physics, the winding can be directly observed. The effects of loss on the experimental results, and on the topological edge states, is discussed.Comment: 10 pages, 10 figure

Mössbauer characterization of microbially mediated iron and manganese ores of variable geological ages

A combination of various techniques was applied to investigate the mineralogy of the Neoproterozoic Urucum iron and manganese deposit (Brazil) and Carboniferous and Permian manganese carbonate deposits (China). The examined deposits exhibited signs of microbial mediation from Fe and Mn bacteria and cyanobacteria. The studied samples showed diversity in their composition and particle size. Probes from Urucum deposit revealed that the rocks consist mainly of hematite, showing Mn substitution which reflects the oxidation of Mn on the active surface of Fe-rich biomat. Nanominerals occurring in significant concentration also supported the microbial contribution to the formation of these ores. Representative samples of Neoproterozoic and Permian deposits showed considerable amount of mixed carbonates with variable composition. 57Fe Mössbauer spectroscopy analysis supported by X-ray diffraction and transmission electron microscopy data provided a detailed characterization of Fe-rich mineral phases of the samples, including metal ratio outlooks, particle size dimension and presence and type of impurities. Integrity and high resolution of the methods allowed to determine new features of the samples reflecting important signatures of microbial activity revealing the biogeochemistry of the biomat formation

Purine synthesis promotes maintenance of brain tumor initiating cells in glioma

Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility. In contrast, differentiated glioma cells were unaffected by the targeting of purine biosynthetic enzymes, suggesting selective dependence of BTICs. MYC coordinated the control of purine synthetic enzymes, supporting its role in metabolic reprogramming. Elevated expression of purine synthetic enzymes correlated with poor prognosis in glioblastoma patients. Collectively, our results suggest that stem-like glioma cells reprogram their metabolism to self-renew and fuel the tumor hierarchy, revealing potential BTIC cancer dependencies amenable to targeted therapy

Group A Streptococcus Secreted Esterase Hydrolyzes Platelet-Activating Factor to Impede Neutrophil Recruitment and Facilitate Innate Immune Evasion

The innate immune system is the first line of host defense against invading organisms. Thus, pathogens have developed virulence mechanisms to evade the innate immune system. Here, we report a novel means for inhibition of neutrophil recruitment by Group A Streptococcus (GAS). Deletion of the secreted esterase gene (designated sse) in M1T1 GAS strains with (MGAS5005) and without (MGAS2221) a null covS mutation enhances neutrophil ingress to infection sites in the skin of mice. In trans expression of SsE in MGAS2221 reduces neutrophil recruitment and enhances skin invasion. The sse deletion mutant of MGAS5005 (ΔsseMGAS5005) is more efficiently cleared from skin than the parent strain. SsE hydrolyzes the sn-2 ester bond of platelet-activating factor (PAF), converting biologically active PAF into inactive lyso-PAF. KM and kcat of SsE for hydrolysis of 2-thio-PAF were similar to those of the human plasma PAF acetylhydrolase. Treatment of PAF with SsE abolishes the capacity of PAF to induce activation and chemotaxis of human neutrophils. More importantly, PAF receptor-deficient mice significantly reduce neutrophil infiltration to the site of ΔsseMGAS5005 infection. These findings identify the first secreted PAF acetylhydrolase of bacterial pathogens and support a novel GAS evasion mechanism that reduces phagocyte recruitment to sites of infection by inactivating PAF, providing a new paradigm for bacterial evasion of neutrophil responses