Slip pulse and resonance of the Kathmandu basin during the 2015 Gorkha earthquake, Nepal

Detailed geodetic imaging of earthquake ruptures enhances our understanding of earthquake physics and associated ground shaking. The 25 April 2015 moment magnitude 7.8 earthquake in Gorkha, Nepal was the first large continental megathrust rupture to have occurred beneath a high-rate (5-hertz) Global Positioning System (GPS) network. We used GPS and interferometric synthetic aperture radar data to model the earthquake rupture as a slip pulse ~20 kilometers in width, ~6 seconds in duration, and with a peak sliding velocity of 1.1 meters per second, which propagated toward the Kathmandu basin at ~3.3 kilometers per second over ~140 kilometers. The smooth slip onset, indicating a large (~5-meter) slip-weakening distance, caused moderate ground shaking at high frequencies (>1 hertz; peak ground acceleration, ~16% of Earth’s gravity) and minimized damage to vernacular dwellings. Whole-basin resonance at a period of 4 to 5 seconds caused the collapse of tall structures, including cultural artifacts

Asperities and barriers on the seismogenic zone in North Chile: state-of-the-art after the 2007 Mw 7.7 Tocopilla earthquake inferred by GPS and InSAR data

The Mw 7.7 2007 November 14 earthquake had an epicentre located close to the city of Tocopilla, at the southern end of a known seismic gap in North Chile. Through modelling of Global Positioning System (GPS) and radar interferometry (InSAR) data, we show that this event ruptured the deeper part of the seismogenic interface (30–50 km) and did not reach the surface. The earthquake initiated at the hypocentre and was arrested ~150 km south, beneath the Mejillones Peninsula, an area already identified as an important structural barrier between two segments of the Peru–Chile subduction zone. Our preferred models for the Tocopilla main shock show slip concentrated in two main asperities, consistent with previous inversions of seismological data. Slip appears to have propagated towards relatively shallow depths at its southern extremity, under the Mejillones Peninsula. Our analysis of post-seismic deformation suggests that small but still significant post-seismic slip occurred within the first 10 d after the main shock, and that it was mostly concentrated at the southern end of the rupture. The post-seismic deformation occurring in this period represents ~12–19 per cent of the coseismic deformation, of which ~30–55 per cent has been released aseismically. Post-seismic slip appears to concentrate within regions that exhibit low coseismic slip, suggesting that the afterslip distribution during the first month of the post-seismic interval complements the coseismic slip. The 2007 Tocopilla earthquake released only ~2.5 per cent of the moment deficit accumulated on the interface during the past 130 yr and may be regarded as a possible precursor of a larger subduction earthquake rupturing partially or completely the 500-km-long North Chile seismic gap

Comparing Petri Net and Activity Diagram Variants for Workflow Modelling:A Quest for Reactive Petri Nets

Petri net variants are widely used as a workflow modelling technique. Recently, UMLa ctivity diagrams have been used for the same purpose, even though the syntax and semantics of activity diagrams has not been yet fully worked out. Nevertheless, activity diagrams seem very similar to Petri nets and on the surface, one may think that they are variants of each other. To substantiate or deny this claim, we need to formalise the intended semantics of activity diagrams and then compare this with various Petri net semantics. In previous papers we have defined two formal semantics for UMLact ivity diagrams that are intended for workflow modelling. In this paper, we discuss the design choices that underlie these two semantics and investigate whether these design choices can be met in low-level and high-level Petri net semantics. We argue that the main difference between the Petri net semantics and our semantics of UML act ivity diagrams is that the Petri net semantics models resource usage of closed, active systems that are non-reactive, whereas our semantics of UMLact ivity diagrams models open, reactive systems. Since workflow systems are open, reactive systems, we conclude that Petri nets cannot model workflows accurately, unless they are extended with a syntax and semantics for reactivity

Anti-Inflammatory Cytokines Predominate in Acute Human Plasmodium knowlesi Infections

Plasmodium knowlesi has entered the human population of Southeast Asia. Naturally acquired knowlesi malaria is newly described with relatively little available data, including data on the host response to infection. Therefore pre-treatment cytokine and chemokine profiles were determined for 94 P. knowlesi, and for comparison, 20, P. vivax and 22 P. falciparum, patients recruited in Malaysian Borneo. Nine, five and one patient with P. knowlesi, P. falciparum and P. vivax respectively had complicated malaria as defined by World Health Organisation. Patients with uncomplicated P. knowlesi had lower levels of the pro-inflammatory cytokines IL-8 and TNFα than those with complicated disease (both p<0.05, Dunn's post test, DPT). The anti-inflammatory cytokines IL-1ra and IL-10 were detected in all patients in the study. IL-1ra, the most abundant cytokine measured, correlated with parasitaemia in P. knowlesi (rs = 0.47, p =  <0.0001), P. vivax (rs = 0.61, p = 0.0042) and P. falciparum (rs = 0.57,p = 0.0054) malaria. IL-10 correlated with parasitaemia in both P. knowlesi (rs = 0.54, p =  <0.0001) and P. vivax (rs = 0.78, p =  <0.0001) infections. There were between group differences in soluble markers of macrophage activation (MIP-1β and MCP-1). P. knowlesi patients had significantly lower levels of MIP-1β than P. falciparum (DPT, p =  <0.01). Uncomplicated P. knowlesi patients had significantly lower levels of MCP-1 than uncomplicated P. falciparum patients (DPT, p =  <0.001). There was no significant difference between complicated and uncomplicated P. knowlesi infections. MCP-1, MIP-1β, IL-8 and TNFα increased in complicated P. knowlesi but decreased in complicated P. falciparum infections. Descriptions of human knowlesi malaria provide a comparative means to discover mediators of pathophysiology in severe P. knowlesi as well as P. falciparum malaria. Crucially, P. knowlesi may be the disease and experimental primate model for severe malaria

Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection

Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria

Keratinocytes as Depository of Ammonium-Inducible Glutamine Synthetase: Age- and Anatomy-Dependent Distribution in Human and Rat Skin

In inner organs, glutamine contributes to proliferation, detoxification and establishment of a mechanical barrier, i.e., functions essential for skin, as well. However, the age-dependent and regional peculiarities of distribution of glutamine synthetase (GS), an enzyme responsible for generation of glutamine, and factors regulating its enzymatic activity in mammalian skin remain undisclosed. To explore this, GS localization was investigated using immunohistochemistry and double-labeling of young and adult human and rat skin sections as well as skin cells in culture. In human and rat skin GS was almost completely co-localized with astrocyte-specific proteins (e.g. GFAP). While GS staining was pronounced in all layers of the epidermis of young human skin, staining was reduced and more differentiated among different layers with age. In stratum basale and in stratum spinosum GS was co-localized with the adherens junction component ß-catenin. Inhibition of, glycogen synthase kinase 3β in cultured keratinocytes and HaCaT cells, however, did not support a direct role of ß-catenin in regulation of GS. Enzymatic and reverse transcriptase polymerase chain reaction studies revealed an unusual mode of regulation of this enzyme in keratinocytes, i.e., GS activity, but not expression, was enhanced about 8–10 fold when the cells were exposed to ammonium ions. Prominent posttranscriptional up-regulation of GS activity in keratinocytes by ammonium ions in conjunction with widespread distribution of GS immunoreactivity throughout the epidermis allows considering the skin as a large reservoir of latent GS. Such a depository of glutamine-generating enzyme seems essential for continuous renewal of epidermal permeability barrier and during pathological processes accompanied by hyperammonemia

Coseismic and postseismic slip associated with the 2010 Maule Earthquake, Chile: Characterizing the Arauco Peninsula barrier effect

[1] Observations of coseismic and postseismic deformation associated with the 2010 Mw = 8.8 Maule earthquake in south-central Chile provide constraints on the spatial heterogeneities of frictional properties on a major subduction megathrust and how they have influenced the seismic rupture and postseismic effects. We find that the bulk of coseismic slip occurs within a single elongated patch approximately 460 km long and 100 km wide between the depths of 15 and 40 km. We infer three major patches of afterslip: one extends northward along strike and downdip of the major coseismic patch between 40 and 60 km depth; the other two bound the northern and southern ends of the coseismic patch. The southern patch offshore of the Arauco Peninsula is the only place showing resolvable afterslip shallower than 20 km depth. Estimated slip potency associated with postseismic slip in the 1.3 years following the earthquake amounts to 20–30% of that generated coseismically. Our estimates of the megathrust frictional properties show that the Arauco Peninsula area has positive but relatively low (a−b)σn values (0.01 ~ 0.22 MPa), that would have allowed dynamic rupture propagation into this rate-strengthening area and afterslip. Given the only modestly rate-strengthening megathrust friction in this region, the barrier effect may be attributed to its relatively large size of the rate-strengthening patch. Coseismic and postseismic uplift of the Arauco Peninsula exceeds interseismic subsidence since the time of the last major earthquake in 1835, suggesting that coseismic and postseismic deformation has resulted in some permanent strain in the forearc