The statistics of large earthquakes commonly involve large uncertainties due to the lack of long‐term, robust earthquake recordings. Small‐scale seismic events are abundant and can be used to examine ...variations in fault structure and stress. We report on the connection between stress and microseismic event statistics prior to the possibly smallest earthquakes: those generated in the laboratory. We investigate variations in seismic b value of acoustic emission events during the stress buildup and release on laboratory‐created fault zones. We show that b values mirror periodic stress changes that occur during series of stick‐slip events, and are correlated with stress over many seismic cycles. Moreover, the amount of b value increase associated with slip events indicates the extent of the corresponding stress drop. Consequently, b value variations can be used to approximate the stress state on a fault: a possible tool for the advancement of time‐dependent seismic hazard assessment.
Key Points
series of seismic cycles on structurally‐complex, laboratory‐created faultsb value is connected to applied stress over many seismic cyclesincrease in b value correlates with stress release during failure
Seismicity clusters within fault zones can be connected to the structure, geometric complexity and size of asperities which perturb and intensify the stress field in their periphery. To gain further ...insight into fault mechanical processes, we study stick‐slip sequences in an analog, laboratory setting. Analysis of small scale fracture processes expressed by acoustic emissions (AEs) provide the possibility to investigate how microseismicity is linked to fault heterogeneities and the occurrence of dynamic slip events. The present work connects X‐ray computer tomography (CT) scans of faulted rock samples with spatial maps of b values (slope of the frequency‐magnitude distribution), seismic moments and event densities. Our current experimental setup facilitates the creation of a series of stick‐slips on one fault plane thus allowing us to document how individual stick‐slips can change the characteristics of AE event populations in connection to the evolution of the fault structure. We found that geometric asperities identified in CT scan images were connected to regions of low b values, increased event densities and moment release over multiple stick‐slip cycles. Our experiments underline several parallels between laboratory findings and studies of crustal seismicity, for example, that asperity regions in lab and field are connected to spatial b value anomalies. These regions appear to play an important role in controlling the nucleation spots of dynamic slip events and crustal earthquakes.
Key Points
Geometric asperities are connected to anomalies in acoustic emission statistics
Highly stressed asperities cause seismic events to grow to larger sizes
Acoustic emission statistics show similarities to crustal seismicity
Earthquakes rarely occur in isolation but rather as complex sequences of fore, main and aftershocks. Assessing the associated seismic hazard requires a holistic view of event interactions. We conduct ...frictional sliding experiments on faulted Westerly Granite samples at mid‐crustal stresses to investigate fault damage and roughness effects on aftershock generation. Abrupt laboratory fault slip is followed by periods of extended stress relaxation and aftershocks. Large roughness promotes less co‐seismic slip and high aftershock activity whereas smooth faults promote high co‐seismic slip with few aftershocks. Conditions close to slip instability generate lab‐quake sequences that exhibit similar statistical distributions to natural earthquakes. Aftershock productivity in the lab is linearly related to the residual strain energy on the fault which, in turn, is controlled by the level of surface heterogeneity. We conclude that roughness and damage govern slip stability and seismic energy partitioning between fore, main and aftershocks in lab and nature.
Plain Language Summary
Earthquakes commonly occur as sequences of fore, main and aftershocks rather than isolated events. A complete assessment of seismic hazard thus requires a holistic view of interactions between seismic events. We investigated such event interactions during frictional experiments on Westerly Granite. The samples contained rough and planar fault surfaces and we investigated seismic events, specifically aftershocks after abrupt laboratory slip. We observed that larger roughness promotes less slip on the fault during macroscopic failure but more aftershock activity. Smooth faults, on the other hand, promote more slip in large events with few aftershocks. The statistical characteristics of small lab‐quake sequences and aftershocks are statistically indistinguishable from natural earthquakes. We conclude that roughness and damage govern slip stability and seismic energy partitioning between fore, main and aftershocks in lab and nature.
Key Points
Aftershock productivity in lab experiments is directly correlated with residual stress on the fault after abrupt slip
Both residual stress and aftershock productivity are substantially higher on rough than on smooth faults
Spatio‐temporal clustering of laboratory seismicity in the transitional frictional regime is similar to Southern California seismicity
The formation of fault damage due to slip under high normal stresses can rarely be monitored under in situ conditions. To advance our understanding of microfracture processes, we investigated ...stick‐slip events on Westerly granite samples containing the following: (1) a planar saw cut fault and (2) a fault developed from a fresh fracture surface. We examined temporal changes of seismic moment tensors and b values of acoustic emission (AE) events. During experiment on the saw cut surface, small AEs exhibiting non‐double‐couple components were observed continuously and strong AEs displaying double‐couple components were visible only when approaching the slip onsets. Sliding on naturally fractured surfaces showed, in addition to double‐couple components, significant volumetric contributions, especially during the interslip periods and immediately after stick‐slip events indicating substantial shear‐enhanced compaction within a relatively broad damage zone. The obtained results shed light on how differences in fault structure control the kinematics of microseismicity during different periods of the seismic cycle.
Key Points
Stick slips analyzed using moment tensor inversion of acoustic emissionsStick‐slip sliding processes are clearly controlled by the initial fault stateChanges in b values attributed to the variations in micromechanical processes
Abstract Dynamic failure in the laboratory is commonly preceded by many foreshocks which accompany premonitory aseismic slip. Aseismic slip is also thought to govern earthquake nucleation in nature, ...yet, foreshocks are rare. Here, we examine how heterogeneity due to different roughness, damage and pore pressures affects premonitory slip and acoustic emission characteristics. High fluid pressures increase stiffness and reduce heterogeneity which promotes more rapid slip acceleration and shorter precursory periods, similar to the effect of low geometric heterogeneity on smooth faults. The associated acoustic emission activity in low-heterogeneity samples becomes increasingly dominated by earthquake-like double-couple focal mechanisms. The similarity of fluid pressure increase and roughness reduction suggests that increased stress and geometric homogeneity may substantially shorten the duration of foreshock activity. Gradual fault activation and extended foreshock activity is more likely observable on immature faults at shallow depth.
In a cross‐sectional study, we assessed effects of calcineurin inhibitor (CNI) or rapamycin on T‐regulatory (Treg) cells from children with stable liver (n = 53) or kidney (n = 9) allografts several ...years posttransplant. We analyzed Treg number, phenotype, suppressive function, and methylation at the Treg‐specific demethylation region (TSDR) using Tregs and peripheral blood mononuclear cells. Forty‐eight patients received CNI (39 as monotherapy) and 12 patients received rapamycin (9 as monotherapy). Treg numbers diminished over time on either regimen, but reached significance only with CNI (r =−0.424, p = 0.017). CNI levels inversely correlated with Treg number (r =−0.371, p = 0.026), and positively correlated with CD127+ expression by Tregs (r = 0.437, p = 0.023). Patients with CNI levels >3.6 ng/mL had weaker Treg function than those with levels <3.6 ng/mL, whereas rapamycin therapy positively correlated with Treg numbers (r = 0.628, p = 0.029) and their expression of CTLA4 (r = 0.726, p = 0.041). Overall, CTLA4 expression, TSDR demethylation and an absence of CD127 were important for Treg suppressive function. We conclude that rapamycin has beneficial effects on Treg biology, whereas long‐term and high dose CNI use may impair Treg number, function and phenotype, potentially acting as a barrier to attaining host hyporesponsiveness to an allograft.
In a cross‐sectional clinical study of pediatric liver and kidney transplant recipients, analysis of FOXP3+ Treg cells shows that rapamycin has beneficial effects on Treg parameters, whereas long‐term and high‐dose calcineurin inhibitor use may impair Treg number, function and phenotype, potentially acting as a barrier to attaining host hyporesponsiveness to an allograft.
Pediatric apheresis collection of peripheral blood stem cells for autologous transplantation often requires use of a blood prime. We evaluated the relationship between pre-apheresis blood CD34
counts ...and final CD34
yield with use of a blood prime. Forty patients underwent apheresis stem cell collection in a 5 year period in our hospital, of which 27 required blood priming of the apheresis machine. Despite the blood prime group having significantly higher pre-apheresis CD34
cell counts, this group processed a relatively higher volume of blood due to a higher dilutional effect and collected significantly less than predicted CD34
cell yield. Use of weight-specific collection efficiencies and dilution-adjusted pre-apheresis CD34
counts will help in accurately estimating the whole blood volume to process for PBSC collection and therefore increase efficiency and decrease the overall cost of collection.
Hematopoietic stem (HSC) and progenitor (HPC) cell fate is governed by intrinsic and extrinsic parameters. We examined the impact of hematopoietic niche elements on HSC and HPC function by analyzing ...the combined effect of osteoblasts (OBs) and stromal cells (SCs) on Lineage−Sca-1+CD117+ (LSK) cells. CFU expansion and marrow repopulating potential of cultured Lineage−Sca-1+CD117+ cells were significantly higher in OB compared with SC cultures, thus corroborating the importance of OBs in the competence of the hematopoietic niche. OB-mediated enhancement of HSC and HPC function was reduced in cocultures of OBs and SCs, suggesting that SCs suppressed the OB-mediated hematopoiesis-enhancing activity. Although the suppressive effect of SC was mediated by adipocytes, probably through up-regulation of neuropilin-1, the OB-mediated enhanced hematopoiesis function was elaborated through Notch signaling. Expression of Notch 2, Jagged 1 and 2, Delta 1 and 4, Hes 1 and 5, and Deltex was increased in OB cultures and suppressed in SC and OB/SC cultures. Phenotypic fractionation of OBs did not segregate the hematopoiesis-enhancing activity but demonstrated that this function is common to OBs from different anatomic sites. These data illustrate that OBs promote in vitro maintenance of hematopoietic functions, including repopulating potential by up-regulating Notch-mediated signaling between HSCs and OBs.
Mesenchymal stem cells (MSC) and MSC-like cells hold great promise and offer many advantages for developing effective cellular therapeutics. Current trends indicate that the clinical application of ...MSC will continue to increase markedly. For clinical applications, large numbers of MSC are usually required, ideally in an off-the-shelf format, thus requiring extensive MSC expansion ex vivo and subsequent cryopreservation and banking.
To exploit the full potential of MSC for cell-based therapies requires overcoming significant cell-manufacturing, banking and regulatory challenges. The current review will focus on the identification of optimal cell source for MSC, the techniques for production scale-up, cryopreservation and banking and the regulatory challenges involved.
There has been considerable success manufacturing and cryopreserving MSC at laboratory scale. Surprisingly little attention, however, has been given to translate these technologies to an industrial scale. The development of cost-effective advanced technologies for producing and cryopreserving commercial-scale MSC is important for successful clinical cell therapy.
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