Site Amplification and Attenuation via Downhole Array Seismogram Inversion: A Comparative Study of the 2003 Miyagi-Oki Aftershock Sequence

Weak-motion geotechnical array recordings at 38 stations of the Japanese strong-motion network KiK-Net from the 2003 M_w 7:0 Miyagi-Oki aftershock sequence are used here to quantify the amplification and attenuation effects of near-surface formations to incident seismic motion. Initially, a seismic waveform optimization algorithm is implemented for the evaluation of high-resolution, low-strain velocity (V_s), attenuation (Q_s), and density (ρ) profiles at the sites of interest. Based on the inversion results, V_s versus Q_s correlations are developed, and scattering versus intrinsic attenuation effects are accounted for in their physical interpretation. Surface-to-downhole traditional spectral ratios (SSR), cross-spectral ratios (c-SSR), and horizontal-to-vertical (H/V) site-response estimates are next evaluated and compared, while their effectiveness is assessed as a function of the site conditions classified on the basis of the weighted average Vs of the upper 30 m (V_(s30)) of the formations. Single and reference-station site-response estimates are successively compared to surface-to-rock outcrop amplification spectra and are evaluated by deconvolution of the downhole records based on the inversion results; comparison of the observed SSR and estimated surface-to-rock outcrop amplification spectra illustrates the effects of destructive interference of downgoing waves at the downhole instrument level as a function of the site class. Site amplification factors are successively computed in reference to the National Earthquake Hazards Reduction Program (NEHRP) B–C boundary site conditions (V_(s30) = 760 m/sec), and results are compared to published values developed on the basis of strong-motion data and site-response analyses. Finally, weak-motion SSR estimates are compared to the mainshock spectra, and conclusions are drawn for the implications of soil nonlinearity in the near surface. Results presented in this article suggest that currently employed site classification criteria need to be reevaluated to ensure intraclass consistency in the assessment of amplification potentials and nonlinearity susceptibility of near-surficial soil formations

Dynamic Rupture Simulations Based on the Characterized Source Model of the 2011 Tohoku Earthquake

The 2011 Off the Pacific Coast of Tohoku earthquake (Tohoku earthquake, M_w 9.0) occurred on the Japan Trench and caused a devastating tsunami. Studies of this earthquake have revealed complex features of its rupture process. In particular, the shallow parts of the fault (near the trench) hosted large slip and long period seismic wave radiation, whereas the deep parts of the rupture (near the coast) hosted smaller slip and strong radiation of short period seismic waves. Understanding such depth-dependent feature of the rupture process of the Tohoku earthquake is necessary as it may occur during future mega-thrust earthquakes in this and other regions. In this study, we investigate the “characterized source model” of the Tohoku earthquake through dynamic rupture simulations. This source model divides the fault plane into several parts characterized by different size and frictional strength (main asperity, background area, etc.) and is widely used in Japan for the prediction of strong ground motion and tsunami through kinematic rupture simulations. Our characterized source model of the Tohoku earthquake comprises a large shallow asperity with moderate frictional strength, small deep asperities with high frictional strength, a background area with low frictional strength, and an area with dynamic weakening close to the trench (low dynamic friction coefficient as arising from, e.g., thermal pressurization). The results of our dynamic rupture simulation reproduce the main depth-dependent feature of the rupture process of the Tohoku earthquake. We also find that the width of the area close to the trench (equal to the distance from the trench to the shallow asperity, interpreted as the size of the accretionary prism) and the presence of dynamic weakening in this area have a significant influence on the final slip distribution. These results are useful to construct characterized source models for other subduction zones with different scale of the accretionary prism, such as the Chile subduction zone and the Nankai Trough. Dynamic rupture simulations based on the characterized source model might provide useful insights for hazard assessment associated with future mega-thrust earthquakes

Structural polymorphisms within a common powdery mildew effector scaffold as a driver of coevolution with cereal immune receptors

In plants, host-pathogen coevolution often manifests in reciprocal, adaptive genetic changes through variations in host nucleotide-binding leucine-rich repeat immune receptors (NLRs) and virulence-promoting pathogen effectors. In grass powdery mildew (PM) fungi, an extreme expansion of a RNase-like effector family, termed RALPH, dominates the effector repertoire, with some members recognized as avirulence (AVR) effectors by cereal NLR receptors. We report the structures of the sequence-unrelated barley PM effectors AVR$_{A6}$, AVR$_{A7}$, and allelic AVR$_{A10}$/AVR$_{A22}$ variants, which are detected by highly sequence-related barley NLRs MLA6, MLA7, MLA10, and MLA22 and of wheat PM AVR$_{PM2}$ detected by the unrelated wheat NLR PM2. The AVR effectors adopt a common scaffold, which is shared with the RNase T1/F1 family. We found striking variations in the number, position, and length of individual structural elements between RALPH AVRs, which is associated with a differentiation of RALPH effector subfamilies. We show that all RALPH AVRs tested have lost nuclease and synthetase activities of the RNase T1/F1 family and lack significant binding to RNA, implying that their virulence activities are associated with neo-functionalization events. Structure-guided mutagenesis identified six AVR$_{A6}$ residues that are sufficient to turn a sequence-diverged member of the same RALPH subfamily into an effector specifically detected by MLA6. Similar structure-guided information for AVR$_{A10}$ and AVR$_{A22}$ indicates that MLA receptors detect largely distinct effector surface patches. Thus, coupling of sequence and structural polymorphisms within the RALPH scaffold of PMs facilitated escape from NLR recognition and potential acquisition of diverse virulence functions

Network Properties of Robust Immunity in Plants

Two modes of plant immunity against biotrophic pathogens, Effector Triggered Immunity (ETI) and Pattern-Triggered Immunity (PTI), are triggered by recognition of pathogen effectors and Microbe-Associated Molecular Patterns (MAMPs), respectively. Although the jasmonic acid (JA)/ethylene (ET) and salicylic acid (SA) signaling sectors are generally antagonistic and important for immunity against necrotrophic and biotrophic pathogens, respectively, their precise roles and interactions in ETI and PTI have not been clear. We constructed an Arabidopsis dde2/ein2/pad4/sid2-quadruple mutant. DDE2, EIN2, and SID2 are essential components of the JA, ET, and SA sectors, respectively. The pad4 mutation affects the SA sector and a poorly characterized sector. Although the ETI triggered by the bacterial effector AvrRpt2 (AvrRpt2-ETI) and the PTI triggered by the bacterial MAMP flg22 (flg22-PTI) were largely intact in plants with mutations in any one of these genes, they were mostly abolished in the quadruple mutant. For the purposes of this study, AvrRpt2-ETI and flg22-PTI were measured as relative growth of Pseudomonas syringae bacteria within leaves. Immunity to the necrotrophic fungal pathogen Alternaria brassicicola was also severely compromised in the quadruple mutant. Quantitative measurements of the immunity levels in all combinatorial mutants and wild type allowed us to estimate the effects of the wild-type genes and their interactions on the immunity by fitting a mixed general linear model. This signaling allocation analysis showed that, contrary to current ideas, each of the JA, ET, and SA signaling sectors can positively contribute to immunity against both biotrophic and necrotrophic pathogens. The analysis also revealed that while flg22-PTI and AvrRpt2-ETI use a highly overlapping signaling network, the way they use the common network is very different: synergistic relationships among the signaling sectors are evident in PTI, which may amplify the signal; compensatory relationships among the sectors dominate in ETI, explaining the robustness of ETI against genetic and pathogenic perturbations

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676

Arabidopsis CaM Binding Protein CBP60g Contributes to MAMP-Induced SA Accumulation and Is Involved in Disease Resistance against Pseudomonas syringae

Salicylic acid (SA)-induced defense responses are important factors during effector triggered immunity and microbe-associated molecular pattern (MAMP)-induced immunity in plants. This article presents evidence that a member of the Arabidopsis CBP60 gene family, CBP60g, contributes to MAMP-triggered SA accumulation. CBP60g is inducible by both pathogen and MAMP treatments. Pseudomonas syringae growth is enhanced in cbp60g mutants. Expression profiles of a cbp60g mutant after MAMP treatment are similar to those of sid2 and pad4, suggesting a defect in SA signaling. Accordingly, cbp60g mutants accumulate less SA when treated with the MAMP flg22 or a P. syringae hrcC strain that activates MAMP signaling. MAMP-induced production of reactive oxygen species and callose deposition are unaffected in cbp60g mutants. CBP60g is a calmodulin-binding protein with a calmodulin-binding domain located near the N-terminus. Calmodulin binding is dependent on Ca2+. Mutations in CBP60g that abolish calmodulin binding prevent complementation of the SA production and bacterial growth defects of cbp60g mutants, indicating that calmodulin binding is essential for the function of CBP60g in defense signaling. These studies show that CBP60g constitutes a Ca2+ link between MAMP recognition and SA accumulation that is important for resistance to P. syringae

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension