107 research outputs found

    Phenomena of stability of the coal seam roof with a yielding support

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    Purpose. Determining the conditions and parameters for ensuring the stability of the coal seam roof with a yielding support in the area adjacent to face and behind it under the influence of dynamic loads based on the analytical and laboratory studies. Methods. To achieve the purpose set, analytical studies have been carried out using the basic principles of the theory of elasticity and vibrations, the hypothesis of girders and the hinged-block displacement of the stratified rock stratum. Also, the laboratory studies of models from equivalent materials have been performed, in which the coal seam roof is presented in the form of a girder having a yielding support with variable rigidity from the filling material under dynamic load. Findings. As a result of performed studies, the phenomenon has been determined that the condition for the stability of the coal seam roof is a geometric parameter that reflects moving of the girder with a yielding support, under the force impact of a falling load with a known mass and the physical-geometrical characteristics of the deformable system. It has been determined that as a result of a change in the spans length, a change in the flexural rigidity of the girder occurs, which means that the yield influence of the same supports on the stability of the coal seam roof is different. The values have been set and the relationship has been studied of the physical-mechanical characteristics of the filling mass as a yielding support. Originality. It has been proven scientifically that the stress-strain state (SSS) of a system in which the coal seam roof is studied as a girder depends on the physical-geometrical characteristics of the system, as well as the type and place of applying the external load, in case when the law of the girder movement in time is determined. Practical implications. The effective supporting of the undermined rock stratum in the working part of the longwall face and behind the face is achieved by placing the yielding supports in the mined-out space or by using the backfill in the mined-out space while conducting the stope operations, thus, increasing the efficiency of measures to protect the labour of miners in coal mines.Мета. Визначення умов і параметрів забезпечення стійкості покрівлі пласта з податливою опорою у привибійному просторі та позаду очисного вибою під впливом динамічних навантажень на основі аналітичних і лабораторних досліджень. Методика. Для досягнення поставленої мети були виконані аналітичні дослідження із застосуванням основних положень теорії пружності й коливань, гіпотези балок і шарнірно-блокового зсування породної товщі, що розшаровується, а так само лабораторні дослідження моделей з еквівалентних матеріалів, в яких покрівля вугільного пласта представлена у вигляді балки, що має податливу опору змінної жорсткості із закладного матеріалу при динамічному навантаженні. Результати. В результаті виконаних досліджень визначено феномен, що умовою стійкості покрівлі вугільного пласта, є геометричний параметр, що відображає переміщення балки з піддатливою опорою, при силовому впливі падаючого вантажу відомої маси і фізико-геометричні характеристики деформованої системи. Визначено, що в результаті зміни довжини прольотів, відбувається зміна згинальної жорсткості балки, а значить вплив податливості одних і тих же опор, на стійкість покрівлі вугільного пласта різний. Встановлено величини і досліджено взаємозв’язок фізико-механічних характеристик закладного масиву як піддатливої опори. Наукова новизна. Науково доведено, що напружено-деформований стан системи, в якій покрівля вугільного пласта досліджується як балка, залежить від фізико-геометричних характеристик системи, виду і місця докладання зовнішнього навантаження, коли визначено закон руху балки в часі. Практична значимість. Ефективне підтримання підробленої породної товщі в робочій частині лави і позаду очисного забою, досягається за рахунок розміщення у виробленому просторі піддатливих опор або застосування закладки виробленого простору при веденні очисних робіт, що так само підвищує ефективність заходів з охорони праці гірників у вугільних шахтах.Цель. Определение условий и параметров обеспечения устойчивости кровли пласта с податливой опорой в призабойном пространстве и позади очистного забоя под воздействием динамических нагрузок на основе аналитических и лабораторных исследований. Методика. Для достижения поставленной цели были выполнены аналитические исследования с применением основных положений теории упругости и колебаний, гипотезы балок и шарнирно-блокового сдвижения расслоившейся породной толщи, а также лабораторные исследования моделей из эквивалентных материалов, в которых кровля угольного пласта представлена в виде балки, имеющей податливую опору переменной жесткости из закладочного материала при динамической нагрузке. Результаты. В результате выполненных исследований определен феномен, что условием устойчивости кровли угольного пласта является геометрический параметр, отражающий перемещение балки с податливой опорой, при силовом воздействии падающего груза известной массы и физико-геометрические характеристики деформируемой системы. Определено, что в результате изменения длины пролетов, происходит изменение изгибной жесткости балки, а значит влияние податливости одних и тех же опор, на устойчивость кровли угольного пласта различно. Установлены величины и исследована взаимосвязь физико-механических характеристик закладочного массива как податливой опоры. Научная новизна. Научно доказано, что напряженно-деформированное состояние системы, в которой кровля угольного пласта исследуется как балка, зависит от физико- геометрических характеристик системы, вида и места приложения внешней нагрузки, когда определен закон движения балки во времени. Практическая значимость. Эффективное поддержание подработанной породной толщи в рабочей части лавы и позади очистного забоя, достигается за счет размещения в выработанном пространстве податливых опор или применения закладки выработанного пространства при ведении очистных работ, что так же повышает эффективность мероприятий по охране труда горнорабочих в угольных шахтах.The authors express their gratitude to the staff of the Mining Department of Donetsk National Technical University and Krasnoarmiisk (Pokrovsk) Industrial Institute for assistance in conducting the laboratory research

    A COMPREHENSIVE STUDY OF THE STABILITY OF LATERAL ROCKS WITH A SUPPLE SUPPORT

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    A complex of analytical studies of the stability of lateral rocks with a supple support, where the coal seam roof was a beam model, some laboratory experiments on samples made from optical and equivalent materials, as well as some mine experiments were was carried out. As a result of the studies, it was found that the stability of lateral rocks with a supple support of crushed rock depended on the compaction of the backfill array on which the roof rocks were based. It was experimentally proved that with external force, the coefficient of compaction of the backfill array changes according to the hyperbolic dependence, the maximum values of which were determined as a result of compaction of the supple support consisting of heterogeneous fractions of the starting material of a certain bulk density. The change in the stress-strain state of the lateral rocks in the coal array with a roadway depended on the bending stiffness of the stratified rock mass and the parameters of flexible structures used to support the roadway. When supporting the roadways with supple support structures, the convergence of the lateral rocks on the contour of the stoop roadway was observed exponentially until the support was completely compressed, while supporting the roadways with coal pillars, the displacement of the rocks on the contour of the roadway increased having linear dependence due to the destruction of the pillar. The stability of the lateral rocks, which determines the operational state of the excavation roadways, was ensured by the use of supple supports or stowing the mined-out space, taking into account the reasonable granulometric content of crushed rock, which ensured the maximum values of the compaction coefficient of the backfill array when the roof and coal seat got deformed.A complex of analytical studies of the stability of lateral rocks with a supple support, where the coal seam roof was a beam model, some laboratory experiments on samples made from optical and equivalent materials, as well as some mine experiments were was carried out. As a result of the studies, it was found that the stability of lateral rocks with a supple support of crushed rock depended on the compaction of the backfill array on which the roof rocks were based. It was experimentally proved that with external force, the coefficient of compaction of the backfill array changes according to the hyperbolic dependence, the maximum values of which were determined as a result of compaction of the supple support consisting of heterogeneous fractions of the starting material of a certain bulk density. The change in the stress-strain state of the lateral rocks in the coal array with a roadway depended on the bending stiffness of the stratified rock mass and the parameters of flexible structures used to support the roadway. When supporting the roadways with supple support structures, the convergence of the lateral rocks on the contour of the stoop roadway was observed exponentially until the support was completely compressed, while supporting the roadways with coal pillars, the displacement of the rocks on the contour of the roadway increased having linear dependence due to the destruction of the pillar. The stability of the lateral rocks, which determines the operational state of the excavation roadways, was ensured by the use of supple supports or stowing the mined-out space, taking into account the reasonable granulometric content of crushed rock, which ensured the maximum values of the compaction coefficient of the backfill array when the roof and coal seat got deformed

    Customized CMOS wavefront sensor

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    We report on an integrated Hartmann wavefront sensor (WFS) using passive-pixel architecture and pixels clustered as position-sensitive detectors for dynamic wavefront analysis. This approach substitutes a conventional imager, such as a CCD or CMOS imager, by a customized detector, thus improving the overall speed performance. CMOS (complementary-metal- oxide-semiconductor) technology enables on-chip integration of several analog and digital circuitry. The sensor performance depends on the feature size of the technology, noise levels, photosensitive elements employed, architecture chosen and reconstruction algorithm.(undefined

    Suppression of Ribosomal Function Triggers Innate Immune Signaling through Activation of the NLRP3 Inflammasome

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    Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by inducing efflux of cellular potassium. Loss of cellular potassium is known to potently suppress protein synthesis, leading us to test whether the inhibition of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of IL-1ß from cells in response to these agents was detected by immunoblotting and ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition of translation by each of the tested translation inhibitors led to processing of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are known to activate the NLRP3 inflammasome, also substantially inhibited protein translation, supporting a close association between inhibition of translation and inflammasome activation. These data demonstrate that translational inhibition itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent inflammatory signaling and that other physical, chemical, or pathogen-associated agents that impair translation may lead to IL-1ß-dependent inflammation through activation of the NLRP3 inflammasome. For agents that inhibit translation through decreased cellular potassium, the application of high extracellular potassium restores protein translation and suppresses activation of the NLRP inflammasome. For agents that inhibit translation through mechanisms that do not involve loss of potassium, high extracellular potassium suppresses IL-1ß processing through a mechanism that remains undefined

    Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent

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    <p>Abstract</p> <p>Background</p> <p>Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action.</p> <p>Methods</p> <p>In this study, microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 μg/ml Onconase for 24 h. A total of 155 genes were found to be regulated by Onconase that were common to both epithelial and biphasic MM cell lines. Some of these genes are known to significantly affect apoptosis (IL-24, TNFAIP3), transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1) or inflammation and the immune response (IL-6, COX-2). RT-PCR analysis of selected up- or down-regulated genes treated with varying doses and times of Onconase generally confirmed the expression array findings in four MM cell lines.</p> <p>Results</p> <p>Onconase treatment consistently resulted in up-regulation of IL-24, previously shown to have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive MM cell lines, as defined by DNA fragmentation analysis. In addition to apoptosis, gene ontology analysis indicated that pathways impacted by Onconase include MAPK signaling, cytokine-cytokine-receptor interactions, and Jak-STAT signaling.</p> <p>Conclusions</p> <p>These results provide a broad picture of gene activity after treatment with a drug that targets small non-coding RNAs and contribute to our overall understanding of MM cell response to Onconase as a therapeutic strategy. The findings provide insights regarding mechanisms that may contribute to the efficacy of this novel drug in clinical trials of MM patients who have failed first line chemotherapy or radiation treatment.</p

    Sulforaphane Potentiates RNA Damage Induced by Different Xenobiotics

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    Background: The isothiocyanate sulforaphane (SFN) possesses interesting anticancer activities. However, recent studies reported that SFN promotes the formation of reactive oxygen species (ROS) as well as DNA breakage. Methodology/Principal Findings: We investigated whether SFN is able to damage RNA, whose loss of integrity was demonstrated in different chronic diseases. Considering the ability of SFN to protect from genotoxicity, we also examined whether SFN is able to protect from RNA damage induced by different chemicals (doxorubicin, spermine, S-nitroso-Nacetylpenicillamine, H2O2). We observed that SFN was devoid of either RNA damaging and RNA protective activity in human leukemic cells. It was able to potentiate the RNA damage by doxorubicin and spermine. In the first case, the effect was attributable to its ability of modulating the bioreductive activation of doxorubicin. For spermine, the effects were mainly due to its modulation of ROS levels produced by spermine metabolism. As to the cytotoxic relevance of the RNA damage, we found that the treatment of cells with a mixture of spermine or doxorubicin plus SFN increased their proapoptotic potential. Thus it is conceivable that the presence of RNA damage might concur to the overall toxic response induced by a chemical agent in targeted cells. Conclusions/Significance: Since RNA is emerging as a potential target for anticancer drugs, its ability to enhance spermineand doxorubicin-induced RNA damage and cytotoxicity could represent an additional mechanism for the potentiatin

    Barnase as a New Therapeutic Agent Triggering Apoptosis in Human Cancer Cells

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    RNases are currently studied as non-mutagenic alternatives to the harmful DNA-damaging anticancer drugs commonly used in clinical practice. Many mammalian RNases are not potent toxins due to the strong inhibition by ribonuclease inhibitor (RI) presented in the cytoplasm of mammalian cells.In search of new effective anticancer RNases we studied the effects of barnase, a ribonuclease from Bacillus amyloliquefaciens, on human cancer cells. We found that barnase is resistant to RI. In MTT cell viability assay, barnase was cytotoxic to human carcinoma cell lines with half-inhibitory concentrations (IC(50)) ranging from 0.2 to 13 microM and to leukemia cell lines with IC(50) values ranging from 2.4 to 82 microM. Also, we characterized the cytotoxic effects of barnase-based immunoRNase scFv 4D5-dibarnase, which consists of two barnase molecules serially fused to the single-chain variable fragment (scFv) of humanized antibody 4D5 that recognizes the extracellular domain of cancer marker HER2. The scFv 4D5-dibarnase specifically bound to HER2-positive cells and was internalized via receptor-mediated endocytosis. The intracellular localization of internalized scFv 4D5-dibarnase was determined by electronic microscopy. The cytotoxic effect of scFv 4D5-dibarnase on HER2-positive human ovarian carcinoma SKOV-3 cells (IC(50) = 1.8 nM) was three orders of magnitude greater than that of barnase alone. Both barnase and scFv 4D5-dibarnase induced apoptosis in SKOV-3 cells accompanied by internucleosomal chromatin fragmentation, membrane blebbing, the appearance of phosphatidylserine on the outer leaflet of the plasma membrane, and the activation of caspase-3.These results demonstrate that barnase is a potent toxic agent for targeting to cancer cells

    Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

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    Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus
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