We propose two major revisions on the rate‐ and state‐dependent friction (RSF) law on the basis of rigorous analysis of friction experiments. First, we find that the direct effect coefficient a, a ...parameter playing a central role in the RSF constitutive law, is much larger than the traditional, consensual estimate of less than about 0.01. We derive a lower bound of 0.035 for a directly from stress‐velocity relations measured during carefully designed step tests, without relying on any evolution laws as traditional methods do. After correcting for state changes during the steps, inferred indirectly from observed changes in acoustic transmissivities across the interface, we obtain an estimate of a as large as 0.05. Second, we calculate values of the RSF state variable Φ by feeding the measured shear stress and slip velocity values into the constitutive law. The results showed systematic deviations from predictions of the RSF evolution law of the aging type. This leads us to propose a revised evolution law, which incorporates a previously unknown weakening effect related to the shear stress. We also present additional experiment results to corroborate the presence of this new effect. Forward simulations based on our revised evolution law, combined with the larger, revised value of a, very well explain observed variations in both the shear stress and Φ throughout different phases of experiments, including quasi‐static hold, reloading after a hold, and steady state sliding at different velocities, as well as their mutual transitions, all with an identical set of parameter values.
Key Points
Novel method to estimate the direct effect coefficient of rate/state friction
Revealing a hitherto unknown weakening effect caused by shear stress increase
Revised formula for rate/state friction that can explain observations very well
SUMMARY
Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in ...patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients’ nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients undergoing NAC and subsequent subtotal esophagectomy. Therefore, patients with a low preoperative nutritional status may be at a higher risk of EC recurrence.
Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute ...to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFRα as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFRα + cells represent a cell population distinct from CD56+ myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFRα+ population. Activation of PDGFRα stimulates proliferation of PDGFRα+ cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFRα+ cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFRα+ mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.
With a conservatively estimated 1 million cases of leptospirosis worldwide and a 5-10% fatality rate, the rapid diagnosis of leptospirosis leading to effective clinical and public health decision ...making is of high importance, and yet remains a challenge.
Based on parallel, population-based studies in two leptospirosis-endemic regions in Brazil, a real-time PCR assay which detects lipL32, a gene specifically present in pathogenic Leptospira, was assessed for the diagnostic effectiveness and accuracy. Patients identified by active hospital-based surveillance in Salvador and Curitiba during large urban leptospirosis epidemics were tested. Real-time PCR reactions were performed with DNA-extracted samples obtained from 127 confirmed and 23 unconfirmed cases suspected of leptospirosis, 122 patients with an acute febrile illness other than leptospirosis, and 60 healthy blood donors.
The PCR assay had a limit of detection of 280 Leptospira genomic equivalents/mL. Sensitivity for confirmed cases was 61% for whole blood and 29% for serum samples. Sensitivity was higher (86%) for samples collected within the first 6 days after onset of illness compared to those collected after 7 days (34%). The real-time PCR assay was able to detect leptospiral DNA in blood from 56% of serological non-confirmed cases. The overall specificity of the assay was 99%.
These findings indicate that real-time PCR may be a reliable tool for early diagnosis of leptospirosis, which is decisive for clinical management of severe and life-threatening cases and for public health decision making.
Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute ...to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFRα as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFRα(+) cells represent a cell population distinct from CD56(+) myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFRα(+) population. Activation of PDGFRα stimulates proliferation of PDGFRα(+) cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFRα(+) cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFRα(+) mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.
Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-β superfamily and has several activities that differ from those of other BMPs. We previously found that BMP-3b is ...highly expressed in adipocytes, its level is increased during obesity, and it inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ (PPARγ) in vitro. However, the function of BMP-3b in adipose tissues in vivo remains unknown.
To determine the role of BMP-3b overexpression in adipose tissues in vivo, we generated transgenic mice (BMP-3b Tg) by using a conditional overexpression approach in fatty acid-binding protein 4-expressing adipocytes. We examined BMP-3b Tg mice fed a high-fat diet to elucidate the effects of BMP-3b on obesity. Adipocyte function was evaluated as expression of adipogenic and lipogenic markers in adipose tissue. We also performed glucose and insulin tolerance tests (GTT and ITT, respectively), and biochemical analysis of serum and measured energy expenditure by indirect calorimetry.
BMP-3b Tg mice fed a high-fat diet showed decreases in weight gain, fat-pad mass and adipocyte area, compared with wild-type mice. The adipose tissues of BMP-3b Tg mice showed downregulated expression of PPARγ and its target gene encoding fatty acid translocase/CD36. In addition, BMP-3b Tg mice had decreased blood glucose levels on GTT and ITT, and their serum leptin levels were decreased and adiponectin concentrations were increased. These changes in BMP-3b Tg mice were accompanied by increased energy expenditure, indicated as increased locomotor activity and oxygen consumption.
These results provide in vivo evidence that BMP-3b regulates adipocyte function to cause an anti-obesity effect.
Hepatitis C virus (HCV) subgenotypes 1a and 1b have different impacts on the treatment response to peginterferon plus ribavirin with direct-acting antivirals (DAAs) against patients infected with HCV ...genotype 1, as the emergence rates of resistance mutations are different between these two subgenotypes. In Japan, almost all of HCV genotype 1 belongs to subgenotype 1b.
To determine HCV subgenotype 1a or 1b in Japanese patients infected with HCV genotype 1, real-time PCR-based method and Sanger method were used for the HCV NS5B region. HCV subgenotypes were determined in 90% by real-time PCR-based method. We also analyzed the specific probe regions for HCV subgenotypes 1a and 1b using ultra-deep sequencing, and uncovered mutations that could not be revealed using direct-sequencing by Sanger method. We estimated the prevalence of HCV subgenotype 1a as 1.2-2.5% of HCV genotype 1 patients in Japan.
Although real-time PCR-based HCV subgenotyping method seems fair for differentiating HCV subgenotypes 1a and 1b, it may not be sufficient for clinical practice. Ultra-deep sequencing is useful for revealing the resistant strain(s) of HCV before DAA treatment as well as mixed infection with different genotypes or subgenotypes of HCV.
The presence of fault gouge and the generation of wear material between two sliding rock surfaces plays a critical role in slip weakening and propagation of ruptures along underground brittle shear ...fractures forming ahead of tabular excavations in deep and high stress gold mining. We performed two types of friction experiments: one with a fault gouge layer between two sliding surfaces, and the other without a fault gouge layer ‘rock-on-rock’, both under room dry conditions at slip velocities ranging from ~1.0 mm/s to 1200 mm/s. These friction experiments revealed a remarkable difference in the frictional weakening behaviour, e.g., rock-on-rock friction experiments show weakening behaviour at lower slip velocity (~5 mm/s) and generally has lower frictional strength than those with the intervening fault gouge between sliding surfaces. This study shows that the existence of the fault gouge layer between sliding rock surfaces delays the onset of fault weakening (i.e., slip weakening displacement of gouge layer experiments is larger compared to rock-on-rock experiments). It is proposed that flash heating may be the main active weakening mechanism within both our gouge and rock-on-rock experiments, and provides a feasible account for the observed weakening. The observed slip weakening displacement (Dc) differences may be attributed to the presence of a gouge layer between sliding surfaces, which has many more contacts during sliding compared to rock-on-rock experiments, thus reducing the average slip velocity per contact, consequently, the potential for activation of flash heating which delays the onset of weakening. Here we suggest that we may be able to describe brittle shear fracture rupture propagation process along underground brittle shear zones by conducting low, intermediate and high slip velocity friction experiments with and without an intervening fault gouge between sliding rock surfaces. These findings should have important implications for the modelling of rupture propagation processes in underground shear zones, a phenomenon that influences the severity of rockbursts, and hence the safety of mine workers and mining operations.
We tested a hypothesis that low-load squat training with slow movement and tonic force generation (LST) would increase muscle size and strength but not necessarily power. Healthy young men were ...assigned to LST 50% one-repetition maximum (1-RM) load, 3 s for lowering/lifting without pause: n=9 or low-load normal speed (LN: 50% 1-RM load, 1 s for lowering/lifting with 1-s pause; n=7) groups. Both groups underwent an 8-week squat training program (10 repetitions/set, 3 sets/day, and 3 days/week) using the assigned methods. Before and after the intervention, quadriceps femoris muscle thickness, maximal torque during isometric hip extension and knee extension, 1-RM squat, lifting power from squatting position and rate of electromyography rise (RER) in knee extensors during the task, leg extension power and vertical jump height were measured. After the intervention, the LN group showed no changes in all the variables. The LST group significantly (P<0.05) increased muscle thickness (6-10%), isometric hip extension torque (18%) and 1-RM squat (10%), but not isometric knee extension torque, lifting power and RER, leg extension power and vertical jump height. These results suggest that LST can increase muscle size and task-related strength, but has little effect on power production during dynamic explosive movements.
Corrosion behavior of a harmonic structured SUS304L austenitic stainless steel was examined and compared with nonharmonic structured SUS304L stainless steel and conventional 304 stainless steel in ...3.5 pct NaCl solution. The study was performed using linear polarization, potentiodynamic polarization, cyclic polarization, and a salt fog exposure test for 30 days. Characterization was accomplished using a scanning electron microscope, an electron probe microanalyzer, and Raman spectroscopy. Improved pitting corrosion resistance was found in the case of the harmonic structured steel as compared to that of the nonharmonic and the conventional 304 stainless steel. Harmonically distributed fine-grained structure, less porosity, and higher fraction of passive
α
-FeOOH are attributed to the improvement in corrosion resistance of the harmonic structured steel.
PDF
