Recently, a zero Hall conductance plateau with random domains was experimentally observed in the quantum anomalous Hall (QAH) effect. We study the effects of random domains on the zero Hall plateau ...in QAH insulators. We find that the structure inversion symmetry determines the scaling property of the zero Hall plateau transition in the QAH systems. In the presence of structure inversion symmetry, the zero Hall plateau state shows a quantum-Hall-type critical point, originating from the two decoupled subsystems with opposite Chern numbers. However, the absence of structure inversion symmetry leads to a mixture between these two subsystems, gives rise to a line of critical points, and dramatically changes the scaling behavior. Hereinto, we predict a Berezinskii-Kosterlitz-Thouless-type transition during the Hall conductance plateau switching in the QAH insulators. Our results are instructive for both theoretic understanding of the zero Hall plateau transition and future transport experiments in the QAH insulators.
Successful control of falciparum malaria depends greatly on treatment with artemisinin combination therapies. Thus, reports that resistance to artemisinins (ARTs) has emerged, and that the prevalence ...of this resistance is increasing, are alarming. ART resistance has recently been linked to mutations in the K13 propeller protein. We undertook a detailed kinetic analysis of the drug responses of K13 wild-type and mutant isolates of Plasmodium falciparum sourced from a region in Cambodia (Pailin). We demonstrate that ART treatment induces growth retardation and an accumulation of ubiquitinated proteins, indicative of a cellular stress response that engages the ubiquitin/proteasome system. We show that resistant parasites exhibit lower levels of ubiquitinated proteins and delayed onset of cell death, indicating an enhanced cell stress response. We found that the stress response can be targeted by inhibiting the proteasome. Accordingly, clinically used proteasome inhibitors strongly synergize ART activity against both sensitive and resistant parasites, including isogenic lines expressing mutant or wild-type K13. Synergy is also observed against Plasmodium berghei in vivo. We developed a detailed model of parasite responses that enables us to infer, for the first time, in vivo parasite clearance profiles from in vitro assessments of ART sensitivity. We provide evidence that the clinical marker of resistance (delayed parasite clearance) is an indirect measure of drug efficacy because of the persistence of unviable parasites with unchanged morphology in the circulation, and we suggest alternative approaches for the direct measurement of viability. Our model predicts that extending current three-day ART treatment courses to four days, or splitting the doses, will efficiently clear resistant parasite infections. This work provides a rationale for improving the detection of ART resistance in the field and for treatment strategies that can be employed in areas with ART resistance.
Recently, the search for an axion insulator state in the ferromagnetic-3D topological insulator (TI) heterostructure and MnBi_{2}Te_{4} has attracted intense interest. However, its detection remains ...difficult in experiments. We systematically investigate the disorder-induced phase transition of the axion insulator state in a 3D TI with antiparallel magnetization alignment surfaces. It is found that there exists a 2D disorder-induced phase transition on the surfaces of the 3D TI which shares the same universality class with the quantum Hall plateau to plateau transition. Then, we provide a phenomenological theory which maps the random mass Dirac Hamiltonian of the axion insulator state into the Chalker-Coddington network model. Therefore, we propose probing the axion insulator state by investigating the universal signature of such a phase transition in the ferromagnetic-3D TI heterostructure and MnBi_{2}Te_{4}. Our findings not only show a global phase diagram of the axion insulator state, but also stimulate further experiments to probe it.
We carried out this meta-analysis to demonstrate efficacies of neoadjuvant chemotherapy (NACT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC) patients based on randomized, ...controlled trials (RCTs).
We comprehensively searched electronic databases and manuscripts for RCTs and extracted data from eligible studies for meta-analysis. Overall survival (OS) with hazard ratios (HRs), locoregional recurrence rate (LRR) and distant metastasis rate (DMR) with relative risks (RRs) were concerned using random and/or fixed-effects models. Subgroup and sensitivity analyses were also carried out.
Six trials in NACT group (n = 1418) and five in AC group (n = 1187) were eligible. HR of death for NACT was 0.82 95% confidence interval (CI) 0.69–0.98, P = 0.03, corresponding to an absolute survival gain of 5.13% after 3 years. Significant reduction of DMR (P = 0.0002; RR 0.69, 95% CI 0.56–0.84) was also found from NACT. But no decrease in LRR (P = 0.49; RR 0.90, 95% CI 0.66–1.22) was observed. Patients receiving additional AC had lower LRR (P = 0.03; RR 0.71, 95% CI 0.53–0.96). But no benefit of OS and DMR were seen in AC.
NACT can effectively enhance OS and reduce DMR, not LRR in NPC. And AC only helps to better control locoregional recurrence of NPC.
The Majorana zero mode in the semiconductor-superconductor nanowire is one of the promising candidates for topological quantum computing. Recently, in islands of nanowires, subgap-state energies have ...been experimentally observed to oscillate as a function of the magnetic field, showing a signature of overlapped Majorana bound states. However, the oscillation amplitude either dies away after an overshoot or decays, sharply opposite to the theoretically predicted enhanced oscillations for Majorana bound states. We reveal that a steplike distribution of spin-orbit coupling in realistic devices can induce the decaying Majorana oscillations, resulting from the coupling-induced energy repulsion between the quasiparticle spectra on the two sides of the step. This steplike spin-orbit coupling can also lead to decaying oscillations in the spectrum of the Andreev bound states. For Coulomb-blockade peaks mediated by the Majorana bound states, the peak spacings have been predicted to correlate with peak heights by a π/2 phase shift, which was ambiguous in recent experiments and may be explained by the steplike spin-orbit coupling. Our work will inspire more works to reexamine effects of the nonuniform spin-orbit coupling, which is generally present in experimental devices.
The nonlinear Hall effect is an unconventional response, in which a voltage can be driven by two perpendicular currents in the Hall-bar measurement. Unprecedented in the family of the Hall effects, ...it can survive time-reversal symmetry but is sensitive to the breaking of discrete and crystal symmetries. It is a quantum transport phenomenon that has deep connection with the Berry curvature. However, a full quantum description is still absent. Here we construct a quantum theory of the nonlinear Hall effect by using the diagrammatic technique. Quite different from nonlinear optics, nearly all the diagrams account for the disorder effects, which play decisive role in the electronic transport. After including the disorder contributions in terms of the Feynman diagrams, the total nonlinear Hall conductivity is enhanced but its sign remains unchanged for the 2D tilted Dirac model, compared to the one with only the Berry curvature contribution. We discuss the symmetry of the nonlinear conductivity tensor and predict a pure disorder-induced nonlinear Hall effect for point groups C
, C
, C
, D
, D
in 2D, and T, T
, C
, D
in 3D. This work will be helpful for explorations of the topological physics beyond the linear regime.
K13, the Cytostome, and Artemisinin Resistance Xie, Stanley C.; Ralph, Stuart A.; Tilley, Leann
Trends in parasitology,
June 2020, 2020-Jun, 2020-06-00, 20200601, Letnik:
36, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Artemisinins – the frontline antimalarial drug class – are compromised by emerging resistance, putting at risk the lives of hundreds of thousands of people each year. Resistance is associated with ...mutations in a malaria parasite protein, called Kelch 13 (K13). Recent work suggests that K13 is located at the cytostome (cell mouth) that the parasite uses to take up hemoglobin. Here we explore the proposal that K13 mutations confer artemisinin resistance by dampening hemoglobin endocytosis. This model suggests that the resultant decrease in hemoglobin-derived heme reduces artemisinin activation, which is sufficient to enable parasite survival in the early ring stage of infection. A fuller understanding of the resistance mechanism will underpin efforts to develop alternative antimalarial strategies.
The cytostome (cell mouth) that the parasite uses to take up hemoglobin is the proposed location for the artemisinin-resistance marker Kelch 13 (K13).K13 mutants exhibit disrupted hemoglobin catabolism.Decreased hemoglobin-dependent activation likely underpins K13-mediated artemisinin resistance.Mutations in other endocytic apparatus proteins may underpin alternative resistance mechanisms.K13 mutations have a fitness cost that may prevent full-blown resistance.
Axion insulators possess a quantized axion field θ = π protected by combined lattice and time-reversal symmetry, holding great potential for device applications in layertronics and quantum computing. ...Here, we propose a high-spin axion insulator (HSAI) defined in large spin-s representation, which maintains the same inherent symmetry but possesses a notable axion field θ = (s + 1/2)
π. Such distinct axion field is confirmed independently by the direct calculation of the axion term using hybrid Wannier functions, layer-resolved Chern numbers, as well as the topological magneto-electric effect. We show that the guaranteed gapless quasi-particle excitation is absent at the boundary of the HSAI despite its integer surface Chern number, hinting an unusual quantum anomaly violating the conventional bulk-boundary correspondence. Furthermore, we ascertain that the axion field θ can be precisely tuned through an external magnetic field, enabling the manipulation of bonded transport properties. The HSAI proposed here can be experimentally verified in ultra-cold atoms by the quantized non-reciprocal conductance or topological magnetoelectric response. Our work enriches the understanding of axion insulators in condensed matter physics, paving the way for future device applications.
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