Properties of Dynamic Earthquake Ruptures With Heterogeneous Stress Drop

Earthquake rupture is a notoriously complex process, at all observable scales. We introduce a simplified semi-dynamic crack model to investigate the connection between the statistical properties of stress and those of macroscopic source parameters such as rupture size, seismic moment, apparent stress drop and radiated energy. Rupture initiation is treated consistently with nucleation on a linear slip-weakening fault, whereas rupture propagation and arrest are treated according to the Griffith criterion. The available stress drop is prescribed as a spatially correlated random field and is shown to potentially sustain a broad range of magnitudes. By decreasing the amplitude of the stress heterogeneities or increasing their correlation length the distribution of earthquake sizes presents a transition from Gutenberg- Richter to characteristic earthquake behavior. This transition is studied through a mean-field analysis. The bifurcation to characteristic earthquake behavior is sharp, reminiscent of a first-order phase transition. A lower roll-off magnitude observed in the Gutenberg-Richter regime is shown to depend on the correlation length of the available stress drop, rather than being a direct signature of the nucleation process. More generally, we highlight the possible role of the stress correlation length scale on deviations from earthquake source self-similarity. The present reduced model is a building block towards understanding the effect of structural and dynamic fault heterogeneities on the scaling of source parameters and on basic properties of seismicity

Earthquake source characteristics from dynamic rupture with constrained stochastic fault stress

One of the challenging tasks in predicting near-source ground motion for future earthquakes is to anticipate the spatiotemporal evolution of the rupture process. The final size of an event but also its temporal properties (propagation velocity, slip velocity) depend on the distribution of shear stress on the fault plane. Though these incipient stresses are not known for future earthquakes, they might be sufficiently well characterized in a stochastic sense. We examine the evolution of dynamic rupture in numerical models of a fault subjected to heterogeneous stress fields with varying statistical properties. By exploring the parameter space of the stochastic stress characterization for a large number of random realizations we relate generalized properties of the resulting events to the stochastic stress parameters. The nucleation zone of the simulated earthquake ruptures in general has a complex shape, but its average size is found to be independent of the stress field parameterization and is determined only by the material parameters and the friction law. Furthermore, we observe a sharp transition in event size from small to system-wide events, governed mainly by the standard deviation of the stress field. A simplified model based on fracture mechanics is able to explain this transition. Finally, we find that the macroscopic rupture parameters ( e. g., moment, moment rate, seismic energy) of our catalog of model quakes are generally consistent with observational data

Variability of Near-Field Ground Motion from Dynamic Earthquake Rupture Simulations

This study investigates near-field ground-motion variability due to dynamic rupture models with heterogeneity in the initial shear stress. Ground velocity seismograms are synthesized by convolving the time histories of slip velocity obtained from spontaneous dynamic rupture models with Green’s functions of the medium calculated with a discrete wavenumber/finite-element method. Peak ground velocity (PGV) estimated on the synthetics generally matches well with an empirically derived attenuation relation, whereas spectral acceleration (SA) shows only an acceptable match at periods longer than 1 sec. Using the geometric mean to average the two orthogonal components leads to a systematic bias for the synthetics, in particular at the stations closest to the fault. This bias is avoided by using measures of ground motion that are independent of the sensor orientation. The contribution from stress heterogeneity to the overall ground-motion variability is found to be strongest close to the fault and in the backward directivity region of unilaterally propagating ruptures. In general, the intraevent variability originating from the radiation pattern and the effect of directivity is on the same order or larger than the interevent variability. The interevent ground-motion variability itself is dominated by the hypocenter-station configuration and is influenced only to a lesser extent by the differences in the dynamic rupture process due to the stress heterogeneity. In our modeling approach the hypocenter location is not picked arbitrarily but is determined to be mechanically consistent with the stress heterogeneity through a procedure emulating tectonic stress loading of the fault and nucleation. Compared to the peak ground motion recorded during the 2004 Parkfield, California, earthquake our simulated seismograms show enhanced spatial correlation that may be attributed to the simplicity of the assumed crustal model or to an incomplete representation of the spatial heterogeneity of dynamic rupture parameters. Nevertheless, the intraevent PGV variability in the near-fault region determined for the Parkfield dataset is of the same order of magnitude as for our simulations

ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges

ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32-/- mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32-/- mice or control littermates. Chronic infection of Zbtb32-/- chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads. In contrast, IgA responses and specificities in the intestine, where memory B cells are repeatedly stimulated by commensal bacteria, were similar between Zbtb32-/- mice and control littermates. Finally, an infection and heterologous booster vaccination model revealed no role for ZBTB32 in restraining primary or recall antibody responses against influenza viruses. Thus, ZBTB32 does not limit recall responses to a number of physiological acute challenges, but does restrict antibody levels during chronic viral infections that periodically engage memory B cells. This restriction might selectively prevent recall responses against chronic infections from progressively overwhelming other antibody specificities.National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI99109, R01AI131680, U01AI131349, K08AI04991]; New York Stem Cell FoundationOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Affinity-restricted memory B cells dominate recall responses to heterologous flaviviruses

Memory B cells (MBCs) can respond to heterologous antigens either by molding new specificities through secondary germinal centers (GCs) or selecting pre-existing clones without further affinity maturation. To distinguish these mechanisms in flavivirus infections and immunizations, we studied recall responses to envelope protein domain III (DIII). Conditional deletion of activation induced cytidine deaminase (AID) between heterologous challenges of West Nile, Japanese encephalitis, Zika, and Dengue viruses did not affect recall responses. DIII-specific MBCs were contained mostly within the plasma cell-biased CD80(+) subset and few GCs arose following heterologous boosters, demonstrating that recall responses are confined by pre-existing clonal diversity. Measurement of monoclonal antibody binding affinity to DIII proteins, timed AID deletion, single cell RNA-sequencing, and lineage tracing experiments point to selection of relatively low affinity MBCs as a mechanism to promote diversity. Engineering immunogens to avoid this MBC diversity may facilitate flavivirus type-specific vaccines with minimized potential for infection enhancement

Building block libraries and structural considerations in the self-assembly of polyoxometalate and polyoxothiometalate systems

Inorganic metal-oxide clusters form a class of compounds that are unique in their topological and electronic versatility and are becoming increasingly more important in a variety of applications. Namely, Polyoxometalates (POMs) have shown an unmatched range of physical properties and the ability to form structures that can bridge several length scales. The formation of these molecular clusters is often ambiguous and is governed by self-assembly processes that limit our ability to rationally design such molecules. However, recent years have shown that by considering new building block principles the design and discovery of novel complex clusters is aiding our understanding of this process. Now with current progress in thiometalate chemistry, specifically polyoxothiometalates (POTM), the field of inorganic molecular clusters has further diversified allowing for the targeted development of molecules with specific functionality. This chapter discusses the main differences between POM and POTM systems and how this affects synthetic methodologies and reactivities. We will illustrate how careful structural considerations can lead to the generation of novel building blocks and further deepen our understanding of complex systems

A non-canonical E-box within the MyoD core enhancer is necessary for circadian expression in skeletal muscle

The myogenic differentiation 1 (MyoD) gene is a master regulator of myogenesis. We previously reported that the expression of MyoD mRNA oscillates over 24 h in skeletal muscle and that the circadian clock transcription factors, BMAL1 (brain and muscle ARNT-like 1) and CLOCK (circadian locomotor output cycles kaput), were bound to the core enhancer (CE) of the MyoD gene in vivo. In this study, we provide in vivo and in vitro evidence that the CE is necessary for circadian expression of MyoD in adult muscle. Gel shift assays identified a conserved non-canonical E-box within the CE that is bound by CLOCK and BMAL1. Functional analysis revealed that this E-box was required for full activation by BMAL1/CLOCK and for in vitro circadian oscillation. Expression profiling of muscle of CEloxP/loxP mice found approximately 1300 genes mis-expressed relative to wild-type. Based on the informatics results, we analyzed the respiratory function of mitochondria isolated from wild-type and CEloxP/loxP mice. These assays determined that State 5 respiration was significantly reduced in CEloxP/loxP muscle. The results of this work identify a novel element in the MyoD enhancer that confers circadian regulation to MyoD in skeletal muscle and suggest that loss of circadian regulation leads to changes in myogenic expression and downstream mitochondrial function

CHD1 Remodels Chromatin and Influences Transient DNA Methylation at the Clock Gene frequency

Circadian-regulated gene expression is predominantly controlled by a transcriptional negative feedback loop, and it is evident that chromatin modifications and chromatin remodeling are integral to this process in eukaryotes. We previously determined that multiple ATP–dependent chromatin-remodeling enzymes function at frequency (frq). In this report, we demonstrate that the Neurospora homologue of chd1 is required for normal remodeling of chromatin at frq and is required for normal frq expression and sustained rhythmicity. Surprisingly, our studies of CHD1 also revealed that DNA sequences within the frq promoter are methylated, and deletion of chd1 results in expansion of this methylated domain. DNA methylation of the frq locus is altered in strains bearing mutations in a variety of circadian clock genes, including frq, frh, wc-1, and the gene encoding the frq antisense transcript (qrf). Furthermore, frq methylation depends on the DNA methyltransferase, DIM-2. Phenotypic characterization of Δdim-2 strains revealed an approximate WT period length and a phase advance of approximately 2 hours, indicating that methylation plays only an ancillary role in clock-regulated gene expression. This suggests that DNA methylation, like the antisense transcript, is necessary to establish proper clock phasing but does not control overt rhythmicity. These data demonstrate that the epigenetic state of clock genes is dependent on normal regulation of clock components

Mutation screening of the RNF8, UBC13 and MMS2 genes in Northern Finnish breast cancer families

<p>Abstract</p> <p>Background</p> <p>Currently known susceptibility genes such as <it>BRCA1 </it>and <it>BRCA2 </it>explain less than 25% of familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. RNF8, UBC13 and MMS2 are involved in the DNA damage response pathway and play important roles in BRCA1-mediated DNA damage recognition. Based on the evidence that several players in the ubiquitin-mediated BRCA1-dependent DDR seem to contribute to breast cancer predisposition, <it>RNF8, UBC13 </it>and <it>MMS2 </it>were considered plausible candidate genes for susceptibility to breast cancer.</p> <p>Methods</p> <p>The entire coding region and splice junctions of <it>RNF8, UBC13 </it>and <it>MMS2 </it>genes were screened for mutations in affected index cases from 123 Northern Finnish breast cancer families by using conformation sensitive gel electrophoresis, high resolution melting (HRM) analysis and direct sequencing.</p> <p>Results</p> <p>Mutation analysis revealed several changes in <it>RNF8 </it>and <it>UBC13</it>, whereas no aberrations were observed in <it>MMS2</it>. None of the found sequence changes appeared to associate with breast cancer susceptibility.</p> <p>Conclusions</p> <p>The present data suggest that mutations in <it>RNF8, UBC13 </it>and <it>MMS2 </it>genes unlikely make any sizeable contribution to breast cancer predisposition in Northern Finland.</p