The proppant is a granular material with a typical size of 0.2 to 1.2 mm. It is used to prevent the closure of fractures in the reservoir created by hydraulic fracturing procedure, which is actively ...used in the oil and gas industry. Some types of proppant are manufactured from porous technical ceramics. Presence of internal voids can dramatically decrease the proppant grain mechanical strength and consequently proppant pack conductivity under natural stress. For a detailed study of proppant particles' internal porosity structure and its relation to the pack's strength, we applied X-ray microtomography (microCT), which allows to observe this structure non-destructively. In the work, we presented our approaches for digital analysis of reconstructed 3D microCT images for studying the internal voids and the homogeneity of their distribution inside the proppant. We used an automatic thresholding for primary segmentation of pores and particles. We apply 3D marker-controlled watershed to separate individual proppant particles. We propose features for characterization of radial and layered porosity distribution for each particle and homogeneity evaluation. The correctness of our method was tested on synthetic models. Current results indicate probable dependence of proppant strength properties on its internal porosity, but not on the homogeneity of porosity distribution.
Heat shock protein (HSP) expression is vital to cellular and tissue protection after stress or injury. However, application of this powerful tool in human disease has been limited, as known enhancers ...of HSPs are toxic and not clinically relevant. Glutamine (GLN) can enhance HSP expression in non-clinically relevant animal injury models. The aim of this study was to assess the ability of GLN to enhance pulmonary HSP expression, attenuate lung injury, and improve survival after sepsis in the rat.
Prospective, randomized, controlled animal trial.
University research laboratory.
Male Sprague-Dawley rats.
We utilized a rat model of cecal ligation and puncture to induce sepsis. GLN or saline was administered 1 hr after initiation of sepsis via single tail-vein injection. We analyzed heat shock factor-1 phosphorylation, HSP-70, and HSP-25 via Western blot. Tissue metabolism was assayed by magnetic resonance spectroscopy. Occurrence of lung injury was determined via histopathologic examination. An inhibitor of HSP expression, quercetin, was utilized to assess role of HSP expression in prevention of sepsis-related mortality.
GLN, given after initiation of sepsis, enhanced pulmonary heat shock factor-1 phosphorylation, HSP-70, HSP-25, and attenuated lung injury after sepsis. Further, GLN improved indices of lung tissue metabolic function (adenosine 5-triphosphate/adenosine 5-diphosphate ratio, nicotinamide adenine dinucleotide) after sepsis. No significant effect of GLN on lung tissue-reduced glutathione was observed. GLN treatment led to a significant decrease in mortality (33% 6 of 18 GLN-treated rats vs. 78% 14 of 17 saline-treated rats). Administration of the HSP inhibitor quercetin blocked GLN-mediated enhancement of HSP expression and abrogated GLN's survival benefit.
GLN has been safely administered to critically ill patients and shown to improve outcome without clear understanding of the protective mechanism. Our results indicate GLN may prevent the occurrence of lung injury, lung tissue metabolic dysfunction, and mortality after sepsis via enhancement of deficient lung heat shock factor-1 phosphorylation/activation and HSP expression.
Neuronal excitotoxicity which is induced by exposure to excessive extracellular glutamate is shown to be involved in neuronal cell death in acute brain injury and a number of neurological diseases. ...High concentration of glutamate induces calcium deregulation which results in mitochondrial calcium overload and mitochondrial depolarization that triggers the mechanism of cell death. Inhibition of mitochondrial calcium uptake could be potentially neuroprotective but complete inhibition of mitochondrial calcium uniporter could result in the loss of some physiological processes linked to Ca
2+
in mitochondria. Here, we found that a novel compound, TG-2112x, can inhibit only the lower concentrations mitochondrial calcium uptake (induced by 100 nM-5 μM) but not the uptake induced by higher concentrations of calcium (10 μM and higher). This effect was not associated with changes in mitochondrial membrane potential and cellular respiration. However, a pre-treatment of neurons with TG-2112x protected the neurons against calcium overload upon application of toxic concentrations of glutamate. Thus, sequestration of mitochondrial calcium uptake protected the neurons against glutamate-induced mitochondrial depolarization and cell death. In our hands, TG-2112x was also protective against ionomycin-induced cell death. Hence, low rate mitochondrial calcium uptake plays an underestimated role in mitochondrial function, and its inhibition could protect neurons against calcium overload and cell death in glutamate excitotoxicity.
Abstract
Various loads have a significant effect on the operation of different equipment components. Modern national and international studies show high efficiency of applying finite element methods ...to research into the loading nature of various parts and systems as a whole. Unevenly distributed loads can reduce the performance of the equipment, as well as lead to the failure of components. This paper examines the effect of the position of the substrate gripper system on the deformations in the printing cylinder. The findings prove that the misalignment of the shaft and gripper bridge placement doubles the resulting deformations.
Oxidative stress and mitochondrial disturbances are the common and important causative factors of aging, and play an important role in the late onset of sporadic neurodegenerative diseases, including ...Alzheimer disease (AD). Furthermore, emerging evidence from in vitro and in vivo disease models suggests that oxidative stress and increased vulnerability to induction of mitochondrial permeability transition leads to the pathogenesis of the neurological disorders. Towards the goals of developing effective neuroprotectors, this article describes the synthesis and neuroprotective studies of various derivatives of the naturally occurring alkaloid securinine, based on which a lead compound, allomargaritarine (a diastereomer of margaritarine), was identified as an effective therapeutic for neuroprotection. Allomargaritarine exhibits high antioxidant activity, and has significant mitoprotective effect on cellular models of neurodegeneration.
Septic shock leads to derangement of cellular metabolism. Enhanced heat shock protein 70 (HSP-70) can preserve cellular metabolism after other forms of cellular stress. Glutamine (GLN) can enhance ...lung HSP-70 expression after lethal endotoxemia. However, it is unknown whether GLN can enhance HSP-70 expression and attenuate lung metabolic dysfunction after sublethal endotoxemia. Our aim was to determine whether GLN could upregulate HSP-70 and attenuate metabolic dysfunction in lung tissue after sublethal endotoxemia.
Sprague-Dawley rats were assigned to one of five groups. The first two groups were treated with
Escherichia coli lipopolysaccharide (LPS; 1 mg/kg intravenously). GLN (0.75 g/kg intravenously) or balanced salt solution as a control was administered 5 min after LPS administration. The next two groups of rats were treated with quercetin (HSP-70 inhibitor; 400 mg/kg intraperitoneally) 6 h before LPS administration. The final group received no treatment. Lung tissue was harvested 24-h after LPS and analyzed with immunofluorescence and western blot for HSP-70. Tissue metabolites were quantified by
1H and
31P nuclear magnetic resonance spectroscopy.
GLN compared with balanced salt solution (BSS) administration in LPS-treated animals led to significant increases in lung HSP-70. Increased HSP-70 expression was observed in lung epithelial cells and macrophages. GLN significantly improved the ratio of adenosine triphosphate to adenosine diphosphate in the lung after LPS. Quercetin inhibited a GLN-mediated increase in lung HSP-70 and blocked a beneficial effect of GLN on the ratio of adenosine triphosphate to adenosine diphosphate after LPS.
A single dose of GLN can enhance HSP-70 in pulmonary epithelial cells and macrophages after sublethal endotoxemia. Further, GLN can attenuate endotoxin-induced lung metabolic dysfunction. GLN's beneficial effect on lung tissue after metabolic dysfunction caused by sublethal endotoxemia may be mediated in part by enhanced HSP-70.
Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Protection against I/R injury may occur via preservation of tissue metabolism and ATP content, ...preservation of reduced glutathione, and stimulation of heat shock protein (HSP) synthesis. Supplementation with glutamine (GLN) has been reported to have beneficial effects on all of these protective pathways. Thus, we hypothesized that GLN pretreatment given to the rat in vivo would protect the myocardium against I/R-induced dysfunction.
GLN (0.52 g/kg, intraperitoneally, given as alanine-glutamine dipeptide), alanine alone (0.23 g/kg), or a Ringer's lactate solution (control) was administered to Sprague-Dawley rats 18 hours before heart excision, perfusion, exposure to global ischemia (15 minutes) and reperfusion (1 hour). Tissue metabolites were analyzed via magnetic resonance spectroscopy.
In control and alanine-treated animals, I/R injury resulted in cardiac dysfunction, indicated by a decrease in cardiac output. Administration of GLN 18 hours before I/R injury preserved cardiac output after reperfusion. Metabolic analysis of the myocardial tissue revealed that /R injury led to significant diminution of myocardial tissue glutamate, ATP content, accumulation of myocardial lactate, and a reduction in reduced glutathione content in control animals. GLN significantly reduced the deleterious changes in myocardial metabolism and improved reduced glutathione content. No changes in pre- or post-I/R injury HSP expression were observed after GLN administration.
These observations demonstrate that remote in vivo administration of GLN before cardiac I/R injury can improve post-I/R cardiac function. This effect may be mediated via improved myocardial metabolism and enhanced reduced glutathione content.
Comparison of the cognition-stimulating effects of Dimebon in a wide dose range revealed a non-monotonic and nontrivial wave-like dose-dependence of its activity. Positive results were obtained at ...low (0.02-0.05 mg/kg) or high (5-10 mg/kg) doses of Dimebon, while intermediate doses were ineffective. This type of the dose dependence of the pharmacological effect can indicate that the substance has several targets. This fact should be taken into consideration when selecting the doses and concentrations of the substance and its analogues for further studies, and for planning treatment schemes and administration doses in clinical studies.
An A 6 + B 2 approach was applied for the first time to synthesize novel hyperbranched pyridylphenylene polymers by Diels–Alder cyclocondensation reaction. For this, the first-generation ...pyridylphenylene dendrimer with six ethynyl functionalities (A 6 ) was used as a branching core for the molecule growth. The phenyl-substituted bis(cyclopentadienone)s (B 2 ) of different structures were used as co-monomer in the reaction. A careful choice of reaction conditions allowed us to obtain high molecular weight polymers without undesirable gelation. The molecular weight of the polymers varied in the range of 10 800–80 100 with a polydispersity degree of 1.69 to 4.07 according to SEC analysis. The 1 H and inverse-gated decoupling 13 C NMR combined with heteronuclear single quantum correlation and heteronuclear multiple bond correlation measurements were used to estimate the branching degree of the polymers synthesized.
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