Deterministic and stochastic chaos characterize laboratory earthquakes

We analyze frictional motion for a laboratory fault as it passes through the stability transition from stable sliding to unstable motion. We study frictional stick-slip events, which are the lab equivalent of earthquakes, via dynamical system tools in order to retrieve information on the underlying dynamics and to assess whether there are dynamical changes associated with the transition from stable to unstable motion. We find that the seismic cycle exhibits characteristics of a low-dimensional system with average dimension similar to that of natural slow earthquakes (<5). We also investigate local properties of the attractor and find maximum instantaneous dimension ≳10, indicating that some regions of the phase space require a high number of degrees of freedom (dofs). Our analysis does not preclude deterministic chaos, but the lab seismic cycle is best explained by a random attractor based on rate- and state-dependent friction whose dynamics is stochastically perturbed. We find that minimal variations of 0.05% of the shear and normal stresses applied to the experimental fault influence the large-scale dynamics and the recurrence time of labquakes. While complicated motion including period doubling is observed near the stability transition, even in the fully unstable regime we do not observe truly periodic behavior. Friction's nonlinear nature amplifies small scale perturbations, reducing the predictability of the otherwise periodic macroscopic dynamics. As applied to tectonic faults, our results imply that even small stress field fluctuations (≲150 kPa) can induce coefficient of variations in earthquake repeat time of a few percent. Moreover, these perturbations can drive an otherwise fast-slipping fault, close to the critical stability condition, into a mixed behavior involving slow and fast ruptures

Renal handling of prednisolone/prednisone: effect of steroid dose and llβ-hydroxysteroid dehydrogenase

The purposes of this study were: (1) to determine under steady-state conditions whether the renal clearance of prednisolone is concentration dependent, and (2) to establish whether the urinary excretion of prednisolone and its biologically inactive 11-dehydro metabolite prednisone depend upon the activity of 11β-hydroxysteroid dehydrogenase (11β-OHSD). For that purpose 10 healthy volunteers were infused to steady state over a 13-h period either at a low (11 μg/h × kg) or a high (70 μg/h × kg) rate with prednisolone on two occasions, once without and once with administration of glycyrrhetinic acid, an inhibitor of 11β-OHSD. Prednisolone and prednisone were measured by high-pressure liquid chromatography. Mean renal clearance values of total or unbound prednisolone were several times higher during the high than the low infusion rate. The fractional renal clearance of unbound prednisolone during the high, but not during the low infusion rate exceeded 1. This indicates that in addition to unbound prednisolone, protein-bound prednisolone is excreted in urine at high plasma concentrations. Inhibition of 11β-OHSD increased the urinary ratios of prednisolone/prednisone in all subjects. Conclusions: (1) The renal clearance of prednisolone is concentration dependent; (2) there must be tubular secretion and/or glomerular filtration of prednisolone bound to plasma proteins; (3) the urinary excretion of prednisolone/prednisone is modulated by the activity of 11 β-OHS

The high-frequency signature of slow and fast laboratory earthquakes

Tectonic faults fail through a spectrum of slip modes, ranging from slow aseismic creep to rapid slip during earthquakes. Understanding the seismic radiation emitted during these slip modes is key for advancing earthquake science and earthquake hazard assessment. In this work, we use laboratory friction experiments instrumented with ultrasonic sensors to document the seismic radiation properties of slow and fast laboratory earthquakes. Stick-slip experiments were conducted at a constant loading rate of 8 μm/s and the normal stress was systematically increased from 7 to 15 MPa. We produced a full spectrum of slip modes by modulating the loading stiffness in tandem with the fault zone normal stress. Acoustic emission data were recorded continuously at 5 MHz. We demonstrate that the full continuum of slip modes radiate measurable high-frequency energy between 100 and 500 kHz, including the slowest events that have peak fault slip rates <100 μm/s. The peak amplitude of the high-frequency time-domain signals scales systematically with fault slip velocity. Stable sliding experiments further support the connection between fault slip rate and high-frequency radiation. Experiments demonstrate that the origin of the high-frequency energy is fundamentally linked to changes in fault slip rate, shear strain, and breaking of contact junctions within the fault gouge. Our results suggest that having measurements close to the fault zone may be key for documenting seismic radiation properties and fully understanding the connection between different slip modes

Nm23 expression in endometrial and cervical cancer: inverse correlation with lymph node involvement and myometrial invasion.

The expression of nm23 has been shown to correlate in some solid tumours with their metastatic potential and to be associated with a favourable prognosis in human breast cancer and melanoma. In breast and ovarian cancer nm23 expression is also correlated with lymph node involvement. We analysed the expression of nm23-H1 and -H2 in normal endometrium and in endometrial and cervical cancer by both Northern and Western blotting. Cellular localisation of Nm23-H1 was visualised by immunohistochemistry mostly in the cytoplasm. Both isoforms of Nm23 were present in all the samples analysed, and a clear direct correlation between Nm23-H1 and -H2 levels was evident. Median nm23-H2 levels were higher than than -H1 levels in both tissues. Cervical cancer patients with lymph node involvement were shown to have significantly lower protein levels of Nm23 (P < 0.007 for H1 and P < 0.009 for H2), and a similar trend was also evident in endometrial cancer. Furthermore, the degree of myometrial invasion in endometrial cancer patients was also inversely correlated with Nm23-H1 levels of expression (P < 0.003). Nm23 level may therefore be taken into consideration as a new marker in the prognostic characterisation and in the treatment planning of uterine tumour patients

Mechanisms for slow strengthening in granular materials

Several mechanisms cause a granular material to strengthen over time at low applied stress. The strength is determined from the maximum frictional force F_max experienced by a shearing plate in contact with wet or dry granular material after the layer has been at rest for a waiting time \tau. The layer strength increases roughly logarithmically with \tau -only- if a shear stress is applied during the waiting time. The mechanisms of strengthening are investigated by sensitive displacement measurements and by imaging of particle motion in the shear zone. Granular matter can strengthen due to a slow shift in the particle arrangement under shear stress. Humidity also leads to strengthening, but is found not to be its sole cause. In addition to these time dependent effects, the static friction coefficient can also be increased by compaction of the granular material under some circumstances, and by cycling of the applied shear stress.Comment: 21 pages, 11 figures, submitted to Phys. Rev.

Breakdown pressure and fracture surface morphology of hydraulic fracturing in shale with H2O, CO2 and N2

Slick-water fracturing is the most routine form of well stimulation in shales; however N2, LPG and CO2 have all been used as “exotic” stimulants in various hydrocarbon reservoirs. We explore the use of these gases as stimulants on Green River shale to compare the form and behavior of fractures in shale driven by different gas compositions and states and indexed by breakdown pressure and the resulting morphology of the fracture networks. Fracturing is completed on cylindrical samples containing a single blind axial borehole under simple triaxial conditions with confining pressure ranging from 10 to 25&nbsp;MPa and axial stress ranging from 0 to 35&nbsp;MPa (σ1&nbsp;&gt;&nbsp;σ2&nbsp;=&nbsp;σ3). Results show that: (1) under the same stress conditions, CO2 returns the highest breakdown pressure, followed by N2, and with H2O exhibiting the lowest breakdown pressure; (2) CO2 fracturing, compared to other fracturing fluids, creates nominally the most complex fracturing patterns as well as the roughest fracture surface and with the greatest apparent local damage followed by H2O and then N2; (3) under conditions of constant injection rate, the CO2 pressure build-up record exhibits condensation between ~5 and 7&nbsp;MPa and transits from gas to liquid through a mixed-phase region rather than directly to liquid as for H2O and N2 which do not; (4) there is a positive correlation between minimum principal stress and breakdown pressure for failure both by transverse fracturing (σ3axial) and by longitudinal fracturing (σ3radial) for each fracturing fluid with CO2 having the highest correlation coefficient/slope and lowest for H2O. We explain these results in terms of a mechanistic understanding of breakdown, and through correlations with the specific properties of the stimulating fluids

Metabolic Checkpoints in Rheumatoid Arthritis

Several studies have highlighted the interplay between metabolism, immunity and inflammation. Both tissue resident and infiltrating immune cells play a major role in the inflammatory process of rheumatoid arthritis (RA) via the production of cytokines, adipo-cytokines and metabolic intermediates. These functions are metabolically demanding and require the most efficient use of bioenergetic pathways. The synovial membrane is the primary site of inflammation in RA and exhibits distinctive histological patterns characterized by different metabolism, prognosis and response to treatment. In the RA synovium, the high energy demand by stromal and infiltrating immune cells, causes the accumulation of metabolites, and adipo-cytokines, which carry out signaling functions, as well as activating transcription factors which act as metabolic sensors. These events drive immune and joint-resident cells to acquire pro-inflammatory effector functions which in turn perpetuate chronic inflammation. Whether metabolic changes are a consequence of the disease or one of the causes of RA pathogenesis is still under investigation. This review covers our current knowledge of cell metabolism in RA. Understanding the intricate interactions between metabolic pathways and the inflammatory and immune responses will provide more awareness of the mechanisms underlying RA pathogenesis and will identify novel therapeutic options to treat this disease

Artificial neural networks improve the prediction of Kt/V, follow-up dietary protein intake and hypotension risk in haemodialysis patients

BACKGROUND: Artificial neural networks (ANN) represent a promising alternative to classical statistical and mathematical methods to solve multidimensional non-linear problems. The aim of the study was to compare the performance of ANN in predicting the dialysis quality (Kt/V), the follow-up dietary protein intake and the risk of intradialytic hypotension in haemodialysis patients with that predicted by experienced nephrologists. METHODS: A combined retrospective and prospective observational study was performed in two Swiss dialysis units (80 chronic haemodialysis patients, 480 monthly clinical observations and biochemical test results). Using mathematical models based on linear and logistic regressions as background, ANN were built and then prospectively compared with the ability of six experienced nephrologists to predict the Kt/V and the follow-up protein catabolic rate (PCR) and to detect a Kt/V &lt; 1.30, a follow-up PCR &lt; 1.00 g/kg/day and the occurrence of hypotension. RESULTS: ANN compared with nephrologists gave a more accurate correlation between estimated and calculated Kt/V and follow-up PCR (P&lt;0.001). The same superiority of ANN was also seen in the ability to detect a Kt/V &lt; 1.30, a follow-up PCR &lt; 1.00 g/kg/day and the occurrence of hypotension expressed as a percentage of correct answers, sensitivity, specificity and predictivity. CONCLUSIONS: The use of ANN significantly improves the ability of experienced nephrologists to estimate the Kt/V and the follow-up PCR and to detect a Kt/V &lt; 1.30, a follow-up PCR &lt; 1.00 g/kg/day and the occurrence of intradialytic hypotension

Acute ST-segment elevation myocardial infarction after amoxycillin-induced anaphylactic shock in a young adult with normal coronary arteries: a case report

BACKGROUND: Acute myocardial infarction (MI) following anaphylaxis is rare, especially in subjects with normal coronary arteries. The exact pathogenetic mechanism of MI in anaphylaxis remains unclear. CASE PRESENTATION: The case of a 32-year-old asthmatic male with systemic anaphylaxis, due to oral intake of 500 mg amoxycillin, complicated by acute ST-elevation MI is the subject of this report. Following admission to the local Health Center and almost simultaneously with the second dose of subcutaneous epinephrine (0.2 mg), the patient developed acute myocardial injury. Coronary arteriography, performed before discharge, showed no evidence of obstructive coronary artery disease. In vivo allergological evaluation disclosed strong sensitivity to amoxycillin and the minor (allergenic) determinants of penicillin. CONCLUSION: Acute ST-elevation MI is a rare but potential complication of anaphylactic reactions, even in young adults with normal coronary arteries. Coronary artery spasm appears to be the main causative mechanism of MI in the setting of "cardiac anaphylaxis". However, on top of the vasoactive reaction, a thrombotic occlusion, induced by mast cell-derived mediators and facilitated by prolonged hypotension, cannot be excluded as a possible contributory factor