Moment Tensor Analysis of Acoustic Emissions Induced by Laboratory-based Hydraulic Fracturing in Granite,

Moment Tensors of hydraulically induced AEs: Hydraulic fracturing is an important technique in the development of enhanced geothermal systems and unconventional resources. Although the fracture modes induced by hydraulic fracturing influence the recovery efficiency of the resources, the current understanding of this relationship is insufficient. In this study, we considered the acoustic emissions (AEs) induced during hydraulic fracturing under uniaxial loading conditions in the laboratory, and applied a moment tensor analysis by carefully correcting the coupling condition and directivity of AE transducers. Experiments were conducted for two types of Kurokami–jima granite samples: those with a rift plane perpendicular (Type H) or parallel (Type V) to the expected direction of fracture propagation (i.e. along the loading axis). In the experiments, both sample types experienced a significant number of shear, tensile and compressive events. The dominant fracture mode for Type H samples is found to be tensile events in which the fracture plane is parallel to the loading axis, whereas for Type V samples, shear events are dominant. This difference suggests that the dominant fracture modes induced by hydraulic fracturing are highly dependent on the relationship between the direction of fracture propagation and orientation of pre-existing weak planes

Antiapoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)-aminoindan5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor.

Abstract The anti Parkinson drug, rasagiline [R-(þ)-N-propargyl-1-aminoindan], an inhibitor of type B monoamine oxidase, has been shown to suppress apoptosis induced by neurotoxins and oxidative stress. A series of novel propargylaminoindans with a carbamate moiety to inhibit cholinesterase were developed from phamacophore of rasagiline to protect or rescue deteriorated neurons in Alzheimer's and Lewy Body disease and provide a beneficial effect on the cognitive deficits. Rasagiline analogues were found to protect dopaminergic SH-SY5Y cells against apoptosis induced by peroxynitrite donor. -(3R)-aminoindan-5-yl]-ethyl methyl carbamate, was as effective as rasagiline in preventing apoptosis, followed by its S-enantiomer, TV3279. The anti-apoptotic-neuroprotective activity was shown to reside in the propargylamine and not the carbamate moiety. This resulted in stabilization of the mitochondrial membrane potential, the collapse of which initiates the apoptotic cascade. q 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Propargylamines; Anti-apoptotic activity; Mitochondrial membrane potential; Monoamine oxidase inhibitor; Cholinesterase inhibitor; Parkinson's disease; Alzheimer's disease; Lewy Body disease; Peroxynitrite; Rasagiline; TV3326 Neurodegenerative disorders, such as Parkinson's (PD) and Alzheimer's disease (AD), are characterized by progressive cell death of selective neurons in the brain. Apoptosis is considered to be a common type of neuronal cell death in neurodegenerative diseases that may be induced by various environmental and genetic factors. The apoptotic cascade is activated by tightly controlled step-wise processes and has been proposed to be a target of neurorescue or neuroprotective strategies A series of analogues were synthesized with a carbamate cholinesterase inhibitory moiety in the aminoindan structure of rasagiline with the purpose of preserving its neuroprotective activity Rasagiline and derivatives ( SH-SY5Y cells were incubated with 0.01 -10 mM of propargylamine derivatives for 20 min, then cultured for 18 h in the presence of 250 mM SIN-1, and the morphological changes in the cells were observed by phase-contrast and fluorescence microscopy after staining with PI and Hoechst 33342 The effects of SIN-1 with and without propargylamines were examined on mitochondrial permeability transition pore by measurement of DCm, as reported previously The chemical structures of rasagiline and its derivatives, TV3326, TV3279, TV3218 a (3SR)-aminoindan-5-yl]-ethyl methyl carbamate, without the propargyl moiety and TV 3294 (6-hydroxy-rasagiline), a propargylaminoindan metabolite of TV3326 without a carbamate moiety are shown in The effects of TV3326 and rasagiline on DCm were examined by measurement of the reduction in Rhodamin 123 fluorescence. SIN-1 (250 mM) reduced the fluorescence to 28.3% of control, and the pre-treatment with TV3326 or rasagiline (0.1 -10 mM) prevented the fluorescence reduction, as summarized in The present study on the structure-activity relationship among propargylamines studied shows that the propargyl moiety is responsible for the anti-apoptotic activity. The presence of the carbamate moiety in TV3326 and TV3279, did not affect the antiapoptotic function associated with rasagilin

Early Intake of Radiocesium by Residents Living Near the Tepco Fukushima Dai-ichi Nuclear Power Plant After the Accident. Part 2: Relationship Between Internal Dose and Evacuation Behavior in Individuals

The Tokyo Electric Power Company's Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident exposed members of the public to radiation. This study analyses the relation between personal behavior data obtained from 112 out of 174 subjects who underwent whole-body measurements by the National Institute of Radiological Sciences (NIRS) during the period from 27 June to 28 July 2011 and their committed effective doses (CEDs) from Cs and Cs. The whereabouts of the 112 persons living in municipalities near the FDNPP (mainly, Namie town) on several days in March 2011 are graphed on maps. It was confirmed that most subjects started evacuation promptly and had left the 20-km-radius of the FDNPP by the end of 12 March. The individual CEDs were poorly correlated with the person's distances from the FDNPP at any day in March. Meanwhile, the percentage of persons remaining within the 20-km radius of the FDNPP was 100% at 16:00 on 12 March and 42.9% at 0:00 on 15 March for those with CEDs > 0.1 mSv, whereas the corresponding values were much lower for those with CEDs ≤ 0.1 mSv. This suggests that the time of evacuation would be one of the crucial factors for the early intake; however, more personal behavior data are needed to be analyzed to clarify the relevance to the individual internal dose

Preparatory acoustic emission activity of hydraulic fracture in granite with various viscous fluids revealed by deep learning technique

To investigate the influence of fluid viscosity on the fracturing process, we conducted hydraulic fracturing experiments on Kurokami-jima granite specimens with resins of various viscosities. We monitored the acoustic emission (AE) activity during fracturing and estimated the moment tensor (MT) solutions for 54 727 AE events using a deep learning technique. We observed the breakdown at 14–22 MPa of borehole pressure, which was dependent on the viscosity, as well as two preparatory phases accompanying the expansion of AE-active regions. The first expansion phase typically began at 10–30 per cent of the breakdown pressure, where AEs occurred three-dimensionally surrounding the wellbore and their active region expanded with time towards the external boundaries of the specimen. The MT solutions of these AEs corresponded to crack-opening (tensile) events in various orientations. The second expansion phase began at 90–99 per cent of the breakdown pressure. During this phase, a new planar AE distribution emerged from the borehole and expanded along the maximum compression axis, and the focal mechanisms of these AEs corresponded to the tensile events on the AE-delineating plane. We interpreted that the first phase was induced by fluid penetration into pre-existing microcracks, such as grain boundaries, and the second phase corresponded to the main fracture formation. Significant dependences on fluid viscosity were observed in the borehole pressure at the time of main fracture initiation and in the speed of the fracture propagation in the second phase. The AE activity observed in the present study was fairly complex compared to that observed in previous experiments conducted on tight shale samples. This difference indicates the importance of the interaction between the fracturing fluid and pre-existing microcracks in the fracturing process

Suppressing TGFβ signaling in regenerating epithelia in an inflammatory microenvironment is sufficient to cause invasive intestinal cancer

Genetic alterations in the TGFβ signaling pathway in combination with oncogenic alterations lead to cancer development in the intestines. However, the mechanisms of TGFβ signaling suppression in malignant progression of intestinal tumors have not yet been fully understood. We have examined ApcΔ716 TGFβr2ΔIEC compound mutant mice that carry mutations in Apc and TGFβr2 genes in the intestinal epithelial cells. We found inflammatory microenvironment only in the invasive intestinal adenocarcinomas but not in noninvasive benign polyps of the same mice. We thus treated simple TGFβr2ΔIEC mice with dextran sodium sulfate (DSS) that causes ulcerative colitis. Importantly, these TGFβr2ΔIEC mice developed invasive colon cancer associated with chronic inflammation.Wealso found that TGFβ signaling is suppressed in human colitis-associated colon cancer cells. In the mouse invasive tumors, macrophages infiltrated and expressed MT1-MMP, causingMMP2activation. These results suggest that inflammatory microenvironment contributes to submucosal invasion of TGFβ signaling-repressed epithelial cells through activation of MMP2. We further found that regeneration was impaired in TGFβr2ΔIEC mice for intestinal mucosa damaged by DSS treatment or X-ray irradiation, resulting in the expansion of undifferentiated epithelial cell population. Moreover, organoids of intestinal epithelial cells cultured from irradiated TGFβr2ΔIEC mice formed "long crypts" in Matrigel, suggesting acquisition of an invasive phenotype into the extracellular matrix. These results, taken together, indicate that a simple genetic alteration in the TGFβ signaling pathway in the inflamed and regenerating intestinal mucosa can cause invasive intestinal tumors. Such a mechanism may play a role in the colon carcinogenesis associated with inflammatory bowel disease in humans

Genetic and Phenotypic Landscape of PRPH2-Associated Retinal Dystrophy in Japan

Peripherin-2 (PRPH2) is one of the causative genes of inherited retinal dystrophy. While the gene is relatively common in Caucasians, reports from Asian ethnicities are limited. In the present study, we report 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy. We identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. Variants p.R142W and p.V200E were relatively common in the cohort. The age of onset was generally in the 40’s; however, some patients had earlier onset (age: 5 years). Visual acuity of the patients ranged from hand motion to 1.5 (Snellen equivalent 20/13). The patients showed variable phenotypes such as retinitis pigmentosa, cone-rod dystrophy, and macular dystrophy. Additionally, intrafamilial phenotypic variability was observed. Choroidal neovascularization was observed in three eyes of two patients with retinitis pigmentosa. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort

Neuroprotective Function of Rasagiline and Selegiline, Inhibitors of Type B Monoamine Oxidase, and Role of Monoamine Oxidases in Synucleinopathies

Synucleinopathies are a group of neurodegenerative disorders caused by the accumulation of toxic species of α-synuclein. The common clinical features are chronic progressive decline of motor, cognitive, behavioral, and autonomic functions. They include Parkinson’s disease, dementia with Lewy body, and multiple system atrophy. Their etiology has not been clarified and multiple pathogenic factors include oxidative stress, mitochondrial dysfunction, impaired protein degradation systems, and neuroinflammation. Current available therapy cannot prevent progressive neurodegeneration and “disease-modifying or neuroprotective” therapy has been proposed. This paper presents the molecular mechanisms of neuroprotection by the inhibitors of type B monoamine oxidase, rasagiline and selegiline. They prevent mitochondrial apoptosis, induce anti-apoptotic Bcl-2 protein family, and pro-survival brain- and glial cell line-derived neurotrophic factors. They also prevent toxic oligomerization and aggregation of α-synuclein. Monoamine oxidase is involved in neurodegeneration and neuroprotection, independently of the catalytic activity. Type A monoamine oxidases mediates rasagiline-activated signaling pathways to induce neuroprotective genes in neuronal cells. Multi-targeting propargylamine derivatives have been developed for therapy in various neurodegenerative diseases. Preclinical studies have presented neuroprotection of rasagiline and selegiline, but beneficial effects have been scarcely presented. Strategy to improve clinical trials is discussed to achieve disease-modification in synucleinopathies

Crack Expansion and Fracturing Mode of Hydraulic Refracturing from Acoustic Emission Monitoring in a Small-Scale Field Experiment

We conducted a hydraulic fracturing (HF) experiment at a 500-m-level gallery in Mizunami Underground Research Laboratory in central Japan. We drilled a hole downward from the gallery floor and initially injected water at a flow rate of 10 mL/min in a section of 36 mm in diameter and 160 mm in length that was selected to avoid a pre-existing joint. The first breakdown (BD) occurred at 9.20 MPa, whereupon we increased the flow rate to 30 mL/min and induced a second BD in the form of “refracturing” at 9.79 MPa, larger than the first BD pressure. Acoustic emissions (AEs) monitored with 16 sensors in four boreholes located 1 m away from the HF hole exhibited two-dimensional distributions, which likely delineate a crack induced by the fracturing. Expansions of the regions in which AEs occurred were observed only immediately after the first and second BDs. Many AE events in other periods were distributed within the regions where AE events had already occurred. The initial motion polarities of P-waves indicate that tensile-dominant AE events occurred when the regions expanded and they were distributed primarily on the frontiers of the regions where AE events had already occurred. The experimental results suggest that increasing the injection flow rate is effective for generating new cracks in the refracturing, with the new crack expansions being induced by tensile fracturing