Explore the vast range of titles available.

The 2016 Mw 5.9 Menyuan earthquake occurred near the Haiyuan fault system in the northeastern Tibetan plateau. Although some kinematic properties of this event have been investigated, more dynamic properties still need to be clarified. First, we use the empirical Green's function method to obtain this event's apparent source time functions (ASTFs), which present a bell shape with a duration of 3s and corresponding smooth spectra. We then conduct dynamic rupture simulations, which are well constrained by the seismic and geodetic observations, to explore more in‐depth source properties. The results show that the characteristics of ASTFs can be explained by the self‐arresting rupture model, which implies that the rupture propagation of this event may spontaneously terminate before reaching the barriers. This result suggests that the initial conditions when this earthquake nucleated may have controlled the rupture process. Our work contributes to understanding the stopping mechanism of some moderate earthquake ruptures. Plain Language Summary A quantitative understanding of what controls earthquake rupture propagation is important, helping to estimate the eventual magnitude of a future earthquake and thus has significant implications for earthquake hazard assessment. Previous studies indicate that the complex fault geometry and the heterogeneous material properties of the fault zone can influence earthquake rupture propagation. In this study, we first use the empirical Green's function approach to obtain the single‐peak apparent source time functions for the 2016 Mw 5.9 Menyuan earthquake, and the corresponding spectra have no spectral troughs. We then conduct the spontaneous dynamic rupture simulations, which are well constrained by the geodetic and seismic observations, to reveal more source properties. The features of apparent source time functions can be well explained by the self‐arresting rupture process, which implies that the rupture propagation might spontaneously stop without external interference. This result indicates that this earthquake's rupture propagation might have been deterministic by the initial conditions in which it prepared for rupture. Key Points The apparent source time functions (ASTFs) of the 2016 Mw 5.9 Menyuan earthquake display a bell shape and corresponding smooth spectra The features of ASTFs can be explained by the self‐arresting rupture model, implying that the rupture propagation might spontaneously stop The dynamic rupture simulations are constrained by the interferometric synthetic aperture radar data and strong ground motion observations

Deformation-induced martensitic transformation (DIMT) has been used for designing high-performance alloys to prevent structural failure under static loads. Its effectiveness against fatigue, however, is unclear. This limits the application of DIMT for parts that are exposed to variable loads, although such scenarios are the rule and not the exception for structural failure. Here we reveal the dual role of DIMT in fatigue crack growth through in situ observations. Two antagonistic fatigue mechanisms mediated by DIMT are identified, namely, transformation-mediated crack arresting, which prevents crack growth, and transformation-mediated crack coalescence, which promotes crack growth. Both mechanisms are due to the hardness and brittleness of martensite as a transformation product, rather than to the actual transformation process itself. In fatigue crack growth, the prevalence of one mechanism over the other critically depends on the crack size and the mechanical stability of the parent austenite phase. Elucidating the two mechanisms and their interplay allows for the microstructure design and safe use of metastable alloys that experience fatigue loads. The findings also generally reveal how metastable alloy microstructures must be designed for materials to be fatigue-resistant.

In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-cell stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.

Low-frequency earthquakes are a series of recurring small earthquakes that are thought to compose tectonic tremors. Compared with regular earthquakes of the same magnitude, low-frequency earthquakes have longer source durations and smaller stress drops and slip rates. The mechanism that drives their unusual type of stress accumulation and release processes is unknown. Here, we use phase diagrams of rupture dynamics to explore the connection between low-frequency earthquakes and regular earthquakes. By comparing the source parameters of low-frequency earthquakes from 2001 to 2016 in Parkfield, on the San Andreas Fault, with those from numerical simulations, we conclude that low-frequency earthquakes are earthquakes that self-arrest within the rupture patch without any introduced interference. We also explain the scaling property of low-frequency earthquakes. Our findings suggest a framework for fault deformation in which nucleation asperities can release stress through slow self-arrest processes. Low-frequency earthquakes are a series of small earthquakes with lower dominant frequencies than ordinary earthquakes. By comparing the simulated earthquakes with the real data, we find that low-frequency earthquakes represent an earthquake rupture process that arrests spontaneously.

The recent growth in energy technologies and the management of subsurface reservoirs has led to increased human interaction with the Earth’s crust. One consequence of this is the overall increase of anthropogenic earthquakes. To manage fluid-injection-induced seismicity, in this study, we propose to use an advanced fluid-injection scheme. First, long-term fluid-injection experiments are separated from short-term fluid-injection experiments. Of the short-term experiments, enhanced geothermal systems stimulations have shown a higher propensity to produce larger seismic events compared to hydraulic fracturing in oil and gas. Among the factors discussed for influencing the likelihood of an induced seismic event to occur are injection rate, cumulative injected volume, wellhead pressure, injection depth, stress state, rock type, and proximity to faults. We present and discuss the concept of fatigue hydraulic fracturing at different scales in geothermal applications. In contrast to the conventional hydraulic fracturing with monotonic injection of high-pressure fluids, in fatigue hydraulic fracturing, the fluid is injected in pressure cycles with increasing target pressure, separated by depressurization phases for relaxing the crack tip stresses. During pressurization phases, the target pressure level is modified by pulse hydraulic fracturing generated with a second pump system. This combination of two pumps with multiple-flow rates may allow a more complex fracture pattern to be designed, with arresting and branching fractures, forming a broader fracture process zone. Small-scale laboratory fluid-injection tests on granite cores and intermediate-scale fluid-injection experiments in a hard rock underground test site are described. At laboratory scale, cyclic fluid-injection tests with acoustic emission analysis are reported with subsequent X-ray CT fracture pattern analysis. At intermediate scale, in a controlled underground experiment at constant depth with well-known stress state in granitic rock, we test advanced fluid-injection schemes. The goal is to optimize the fracture network and mitigate larger seismic events. General findings in granitic rock, independent of scale, are summarized. First, the fracture breakdown pressure in fatigue hydraulic testing is lower than that in the conventional hydraulic fracturing. Second, compared to continuous injection, the magnitude of the largest induced seismic event seems to be systematically reduced by cyclic injection. Third, the fracture pattern in fatigue testing is different from that in the conventional injection tests at high pressures. Cyclic fracture patterns seem to result from chiefly generated low energy grain boundary cracks forming a wider process zone. Fourth, cyclic injection increases the permeability of the system. A combination of cyclic progressive and pulse pressurization leads to the best hydraulic performance of all schemes tested. One advantage of fatigue testing is the fact that this soft stimulation method can be applied in circumstances where the conventional stimulation might otherwise be abandoned based on site-specific seismic hazard estimates.

Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19 + CD24 hi CD27 + CD39 hi IgD − IgM + CD1c + B cells is essential for effective immune regulation. Mechanistically, TIGIT on memory B cells controls immune response by directly acting on T cells and by arresting proinflammatory function of dendritic cells, resulting in the suppression of Th1, Th2, Th17, and CXCR5 + ICOS + T cell response while promoting immune regulatory function of T cells. TIGIT + memory B cells are also superior to other B cells at expressing additional inhibitory molecules, including IL-10, TGFβ1, granzyme B, PD-L1, CD39/CD73, and TIM-1. Lack or decrease of TIGIT + memory B cells is associated with increased donor-specific antibody and TFH response, and decreased Treg response in renal and liver allograft patients. Therefore, TIGIT + human memory B cells play critical roles in immune regulation. Regulatory B cells have been shown to play critical roles in the modulation of the immune system. Here, the authors implicate TIGIT expression in B cells with the process of immuno-regulation.

To subvert host defenses, Mycobacterium tuberculosis (Mtb) avoids being delivered to degradative phagolysosomes in macrophages by arresting the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. The SecA2 dependent protein export system is required for phagosome maturation arrest and consequently growth of Mtb in macrophages. To better understand the role of the SecA2 pathway in phagosome maturation arrest, we identified two effectors exported by SecA2 that contribute to this process: the phosphatase SapM and the kinase PknG. Then, utilizing the secA2 mutant of Mtb as a platform to study effector functions, we identified specific steps in phagosome maturation inhibited by SapM and/or PknG. By identifying a histidine residue that is essential for SapM phosphatase activity, we confirmed for the first time that the phosphatase activity of SapM is required for its effects on phagosome maturation in macrophages. We further demonstrated that SecA2 export of SapM and PknG contributes to the ability of Mtb to replicate in macrophages. Finally, we extended our understanding of the SecA2 pathway, SapM, and PknG by revealing that their contribution goes beyond preventing Mtb delivery to mature phagolysosomes and includes inhibiting Mtb delivery to autophagolysosomes. Together, our results revealed SapM and PknG to be two effectors exported by the SecA2 pathway of Mtb with distinct as well as cumulative effects on phagosome and autophagosome maturation. Our results further reveal that Mtb must have additional mechanisms of limiting acidification of the phagosome, beyond inhibiting recruitment of the V-ATPase proton pump to the phagosome, and they indicate differences between effects of Mtb on phagosome and autophagosome maturation.

Pregnancy is widely viewed as dependent upon an intimate dialogue, mediated by locally secreted factors between a developmentally competent embryo and a receptive endometrium. Reproductive success in humans is however limited, largely because of the high prevalence of chromosomally abnormal preimplantation embryos. Moreover, the transient period of endometrial receptivity in humans uniquely coincides with differentiation of endometrial stromal cells (ESCs) into highly specialized decidual cells, which in the absence of pregnancy invariably triggers menstruation. The role of cyclic decidualization of the endometrium in the implantation process and the nature of the decidual cytokines and growth factors that mediate the crosstalk with the embryo are unknown. We employed a human co-culture model, consisting of decidualizing ESCs and single hatched blastocysts, to identify the soluble factors involved in implantation. Over the 3-day co-culture period, approximately 75% of embryos arrested whereas the remainder showed normal development. The levels of 14 implantation factors secreted by the stromal cells were determined by multiplex immunoassay. Surprisingly, the presence of a developing embryo had no significant effect on decidual secretions, apart from a modest reduction in IL-5 levels. In contrast, arresting embryos triggered a strong response, characterized by selective inhibition of IL-1beta, -6, -10, -17, -18, eotaxin, and HB-EGF secretion. Co-cultures were repeated with undifferentiated ESCs but none of the secreted cytokines were affected by the presence of a developing or arresting embryo. Human ESCs become biosensors of embryo quality upon differentiation into decidual cells. In view of the high incidence of gross chromosomal errors in human preimplantation embryos, cyclic decidualization followed by menstrual shedding may represent a mechanism of natural embryo selection that limits maternal investment in developmentally impaired pregnancies.

Arresting gear systems play a vital role in carrier-based aircraft landing. In order to accurately understand the process of arresting hook and cable, this study introduces a parameter inversion method to model the arresting cable and applies it to the transient dynamics model of the arresting hook and cable. The feasibility of the arresting cable model and its application to the transient dynamics model of the arresting hook and cable are validated through arresting hook and cable impact tests. The study compares three different models of arresting cables for simulation results and concludes that assuming the arresting cable to be a beam with metal elastic parameters during the modeling process cannot ignore the influence of the cable’s torsional and bending stiffness on the modeling. The study also investigates the dynamic response of the arresting hook during the aircraft arrestment and hooking process and concludes that the stress peak of the hook arm is much lower throughout the entire arrestment process than at the moment of hooking the cable. The study further identifies factors that affect the stress on the arresting hook arm, such as the aircraft’s yaw angle, deck angle, cruising speed, and the initial position of the arresting hook and cable before engagement. The research results have significant implications for improving the design optimization of the structural strength of the functional components of the naval aircraft arresting system and provide theoretical guidance and technical reserves for subsequent related studies.

Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA) strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15-30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population. Acute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated. A single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis). The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in treating MRSA mediated foot infections in diabetic individuals who do not respond to conventional antibiotic therapy.