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Sample records for rho-associated kinase rock

  1. Peptide substrates for Rho-associated kinase 2 (Rho-kinase 2/ROCK2.

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    Jeong-Hun Kang

    Full Text Available Peptide substrates sensitive for a certain protein kinase could be important for new-drug development and to understand the mechanism of diseases. Rho-associated kinase (Rho-kinase/ROCK is a serine/threonine kinase, and plays an important part in cardiovascular disease, migration and invasion of tumor cells, and in neurological disorders. The purpose of this study was to find substrates with high affinity and sensitivity for ROCK2. We synthesized 136 peptide substrates from protein substrates for ROCK2 with different lengths and charged peptides. Incorporation of (32P [counts per minute (CPM] for each peptide substrate was determined by the radiolabel assay using [γ-(32P]ATP. When the top five peptide substrates showing high CPMs (R4, R22, R133, R134, and R135 were phosphorylated by other enzymes (PKA, PKCα, and ERK1, R22, R133, and R135 displayed the highest CPM level for ROCK2 compared with other enzymes, whereas R4 and R134 showed similar CPM levels for ROCK2 and PKCα. We hypothesize that R22, R133, and R135 can be useful peptide substrates for ROCK2.

  2. Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis.

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    Kümper, Sandra; Mardakheh, Faraz K; McCarthy, Afshan; Yeo, Maggie; Stamp, Gordon W; Paul, Angela; Worboys, Jonathan; Sadok, Amine; Jørgensen, Claus; Guichard, Sabrina; Marshall, Christopher J

    2016-01-14

    Rho-associated kinases 1 and 2 (ROCK1/2) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton, but their role in proliferation and cancer initiation or progression is not known. Here, we provide evidence that ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and cell proliferation and that their loss leads to cell-cycle arrest and cellular senescence. This phenotype arises from down-regulation of the essential cell-cycle proteins CyclinA, CKS1 and CDK1. Accordingly, while the loss of either Rock1 or Rock2 had no negative impact on tumorigenesis in mouse models of non-small cell lung cancer and melanoma, loss of both blocked tumor formation, as no tumors arise in which both Rock1 and Rock2 have been genetically deleted. Our results reveal an indispensable role for ROCK, yet redundant role for isoforms 1 and 2, in cell cycle progression and tumorigenesis, possibly through the maintenance of cellular contractility.

  3. Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis

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    K?mper, Sandra; Mardakheh, Faraz K; McCarthy, Afshan; Yeo, Maggie; Stamp, Gordon W; Paul, Angela; Worboys, Jonathan; Sadok, Amine; J?rgensen, Claus; Guichard, Sabrina; Marshall, Christopher J

    2016-01-01

    eLife digest Animal cells contain a structure called the cytoskeleton, which helps give the cells their shape. This structure can rapidly disassemble and reassemble, which enables cells to change their shape, move and divide into two. Many proteins are involved in controlling these processes. In particular, two proteins called ROCK1 and ROCK2 are known to be important for helping cancer cells move. However, investigations into the exact roles of these proteins have so far produced contradicto...

  4. Rho-associated coiled-coil kinase (ROCK) protein controls microtubule dynamics in a novel signaling pathway that regulates cell migration.

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    Schofield, Alice V; Steel, Rohan; Bernard, Ora

    2012-12-21

    The two members of the Rho-associated coiled-coil kinase (ROCK1 and 2) family are established regulators of actin dynamics that are involved in the regulation of the cell cycle as well as cell motility and invasion. Here, we discovered a novel signaling pathway whereby ROCK regulates microtubule (MT) acetylation via phosphorylation of the tubulin polymerization promoting protein 1 (TPPP1/p25). We show that ROCK phosphorylation of TPPP1 inhibits the interaction between TPPP1 and histone deacetylase 6 (HDAC6), which in turn results in increased HDAC6 activity followed by a decrease in MT acetylation. As a consequence, we show that TPPP1 phosphorylation by ROCK increases cell migration and invasion via modulation of cellular acetyl MT levels. We establish here that the ROCK-TPPP1-HDAC6 signaling pathway is important for the regulation of cell migration and invasion.

  5. MicroRNA-124 (MiR-124 Inhibits Cell Proliferation, Metastasis and Invasion in Colorectal Cancer by Downregulating Rho-Associated Protein Kinase 1(ROCK1

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    Liqing Zhou

    2016-05-01

    Full Text Available Background/Aims: MiR-124 inhibits neoplastic transformation, cell proliferation, and metastasis and downregulates Rho-associated protein kinase (ROCK1 in Colorectal Cancer (CRC. The aim of this study was to further investigate the roles and interactions of ROCK1 and miR-124 and the effects of knockdown of ROCK1and MiR-124 in human Colorectal Cancer (CRC. Methods: Three Colorectal cancer cell lines (HCT116, HT29 and SW620 and one Human Colonic Mucosa Epithelial cell line (NCM460 were studied. The protein expression of ROCK1 was examined by Western-blot and qRT-PCR were performed to examine the expression levels of ROCK1 mRNA and miR-124. Furthermore, We performed transfection of cancer cell line (SW620 with pre-miR-124(mimics, anti-miR-124(inhibitor, ROCK1 siRNA and the control, then observed the affects of ROCK1 protein expression by westen-blot, cell proliferation by EDU (5-ethynyl-2'deoxyuridine assay and expression levels of ROCK1mRNA by qRT-PCR . A soft agar formation assay, Migration and invasion assays were used to determine the effect of regulation of miR-124 and ROCK1, and survivin on the transformation and invasion capability of colorectal cancer cell. Results: MiR-124 expression was significantly downregulated in CRC cell lines compare to normal (P 0.05. ROCK1 mRNA was unaltered in cells transfected with miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a significant reduction in ROCK1 protein in cells transfected with miR-124 mimic and a significant increase in cells transfected with miR-124 inhibitor (P Conclusions: In conclusion, our results demonstrated that miR-124 not only promoted cancer cell hyperplasia and significantly associated with CRC metastasis and progression, but also downregulated ROCK1 protein expression. More importantly, increased ROCK1 expression or inhibited miR-124 expression may constitute effective new therapeutic strategies for the treatment of renal cancer in the future.

  6. Polychlorinated biphenyls (PCBs enhance metastatic properties of breast cancer cells by activating Rho-associated kinase (ROCK.

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    Sijin Liu

    Full Text Available BACKGROUND: Polychlorinated biphenyls (PCBs are a family of structurally related chlorinated aromatic hydrocarbons. Numerous studies have documented a wide spectrum of biological effects of PCBs on human health, such as immunotoxicity, neurotoxicity, estrogenic or antiestrogenic activity, and carcinogenesis. The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo, animal and epidemiologic studies. A number of investigations indicated that higher levels of PCBs in mammary tissues or sera correlated to breast cancer risk, and PCBs might be implicated in advancing breast cancer progression. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, we for the first time report that PCBs greatly promote the ROCK activity and therefore increase cell motility for both non-metastatic and metastatic human breast cancer cells in vitro. In the in vivo study, PCBs significantly advance disease progression, leading to enhanced capability of metastatic breast cancer cells to metastasize to bone, lung and liver. Additionally, PCBs robustly induce the production of intracellular reactive oxygen species (ROS in breast cancer cells; ROS mechanistically elevate ROCK activity. CONCLUSIONS/SIGNIFICANCE: PCBs enhance the metastatic propensity of breast cancer cells by activating the ROCK signaling, which is dependent on ROS induced by PCBs. Inhibition of ROCK may stand for a unique way to restrain metastases in breast cancer upon PCB exposure.

  7. Phosphorylation and mRNA splicing of collapsin response mediator protein-2 determine inhibition of rho-associated protein kinase (ROCK) II function in carcinoma cell migration and invasion

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    Morgan-Fisher, Marie; Couchman, John R; Yoneda, Atsuko

    2013-01-01

    The Rho-associated protein kinases (ROCK I and II) are central regulators of important cellular processes such as migration and invasion downstream of the GTP-Rho. Recently, we reported collapsin response mediator protein (CRMP)-2 as an endogenous ROCK II inhibitor. To reveal how the CRMP-2-ROCK II......, the presented data show that CRMP-2-dependent regulation of ROCK II activity is mediated through interaction of the CRMP-2L N terminus with the ROCK II catalytic domain as well as by GSK3-dependent phosphorylation of CRMP-2....

  8. Rho-associated kinase inhibitors: a novel glaucoma therapy.

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    Inoue, Toshihiro; Tanihara, Hidenobu

    2013-11-01

    The rho-associated kinase (ROCK) signaling pathway is activated via secreted bioactive molecules or via integrin activation after extracellular matrix binding. These lead to polymerization of actin stress fibers and formation of focal adhesions. Accumulating evidence suggests that actin cytoskeleton-modulating signals are involved in aqueous outflow regulation. Aqueous humor contains various biologically active factors, some of which are elevated in glaucomatous eyes. These factors affect aqueous outflow, in part, through ROCK signaling modulation. Various drugs acting on the cytoskeleton have also been shown to increase aqueous outflow by acting directly on outflow tissue. In vivo animal studies have shown that the trabecular meshwork (TM) actin cytoskeleton in glaucomatous eyes is more disorganized and more randomly oriented than in non-glaucomatous control eyes. In a previous study, we introduced ROCK inhibitors as a potential glaucoma therapy by showing that a selective ROCK inhibitor significantly lowered rabbit IOP. Rho-associated kinase inhibitors directly affect the TM and Schlemm's canal (SC), differing from the target sight of other glaucoma drugs. The TM is affected earlier and more strongly than ciliary muscle cells by ROCK inhibitors, largely because of pharmacological affinity differences stemming from regulatory mechanisms. Additionally, ROCK inhibitors disrupt tight junctions, result in F-actin depolymerization, and modulate intracellular calcium level, effectively increasing SC-cell monolayer permeability. Perfusion of an enucleated eye with a ROCK inhibitor resulted in wider empty spaces in the juxtacanalicular (JCT) area and more giant vacuoles in the endothelial cells of SC, while the endothelial lining of SC was intact. Interestingly, ROCK inhibitors also increase retinal blood flow by relaxing vascular smooth muscle cells, directly protecting neurons against various stresses, while promoting wound healing. These additional effects may help

  9. Rho-associated kinase is a therapeutic target in neuroblastoma.

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    Dyberg, Cecilia; Fransson, Susanne; Andonova, Teodora; Sveinbjörnsson, Baldur; Lännerholm-Palm, Jessika; Olsen, Thale K; Forsberg, David; Herlenius, Eric; Martinsson, Tommy; Brodin, Bertha; Kogner, Per; Johnsen, John Inge; Wickström, Malin

    2017-08-08

    Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN -driven neuroblastoma growth in TH- MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.

  10. New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops.

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    Koizumi, Noriko; Okumura, Naoki; Ueno, Morio; Kinoshita, Shigeru

    2014-11-01

    Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal endothelial transplantation. However, despite the value and potential of endothelial graft surgery, a strictly pharmacological approach for treating corneal endothelial dysfunction remains an attractive proposition. Previously, we reported that the selective Rho-associated kinase (ROCK) inhibitor Y-27632 promotes cell adhesion and proliferation, and inhibits the apoptosis of primate corneal endothelial cells in culture. These findings have led us to develop a novel medical treatment for the early phase of corneal endothelial disease using ROCK inhibitor eye drops. In rabbit and monkey models of partial endothelial dysfunction, we showed that corneal endothelial wound healing was accelerated via the topical application of ROCK inhibitor to the ocular surface, resulting in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. Based on these animal studies, we are now attempting to advance the clinical application of ROCK inhibitor eye drops for patients with corneal endothelial dysfunction. A pilot clinical study was performed at the Kyoto Prefectural University of Medicine, and the effects of Y-27632 eye drops after transcorneal freezing were evaluated in 8 patients with corneal endothelial dysfunction. We observed a positive effect of ROCK inhibitor eye drops in treating patients with central edema caused by Fuchs corneal endothelial dystrophy. We believe that our new findings will contribute to the establishment of a new approach for the treatment of corneal endothelial dysfunction.

  11. Crosstalk between Substrates and Rho-Associated Kinase Inhibitors in Cryopreservation of Tissue-Engineered Constructs

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    Arindam Bit

    2017-01-01

    Full Text Available It is documented that human mesenchymal stem cells (hMSCs can be differentiated into various types of cells to present a tool for tissue engineering and regenerative medicine. Thus, the preservation of stem cells is a crucial factor for their effective long-term storage that further facilitates their continuous supply and transportation for application in regenerative medicine. Cryopreservation is the most important, practicable, and the only established mechanism for long-term preservation of cells, tissues, and organs, and engineered tissues; thus, it is the key step for the improvement of tissue engineering. A significant portion of MSCs loses cellular viability while freeze-thawing, which represents an important technical limitation to achieving sufficient viable cell numbers for maximum efficacy. Several natural and synthetic materials are extensively used as substrates for tissue engineering constructs and cryopreservation because they promote cell attachment and proliferation. Rho-associated kinase (ROCK inhibitors can improve the physiological function and postthaw viability of cryopreserved MSCs. This review proposes a crosstalk between substrate topology and interaction of cells with ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the presence of an external electrical field improves the generation of ROCK inhibitors to safeguard cellular viability for the enhanced cryopreservation of engineered tissues.

  12. Rho-associated kinase inhibitors promote the cardiac differentiation of embryonic and induced pluripotent stem cells.

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    Cheng, Ya-Ting; Yeih, Dong-Feng; Liang, Shu-Man; Chien, Chia-Ying; Yu, Yen-Ling; Ko, Bor-Sheng; Jan, Yee-Jee; Kuo, Cheng-Chin; Sung, Li-Ying; Shyue, Song-Kun; Chen, Ming-Fong; Yet, Shaw-Fang; Wu, Kenneth K; Liou, Jun-Yang

    2015-12-15

    Rho-associated kinase (ROCK) plays an important role in maintaining embryonic stem (ES) cell pluripotency. To determine whether ROCK is involved in ES cell differentiation into cardiac and hematopoietic lineages, we evaluated the effect of ROCK inhibitors, Y-27632 and fasudil on murine ES and induced pluripotent stem (iPS) cell differentiation. Gene expression levels were determined by real-time PCR, Western blot analysis and immunofluorescent confocal microscopy. Cell transplantation of induced differentiated cells were assessed in vivo in a mouse model (three groups, n=8/group) of acute myocardial infarction (MI). The cell engraftment was examined by immunohistochemical staining and the outcome was analyzed by echocardiography. Cells were cultured in hematopoietic differentiation medium in the presence or absence of ROCK inhibitor and colony formation as well as markers of ES, hematopoietic stem cells (HSC) and cells of cardiac lineages were analyzed. ROCK inhibition resulted in a drastic change in colony morphology accompanied by loss of hematopoietic markers (GATA-1, CD41 and β-Major) and expressed markers of cardiac lineages (GATA-4, Isl-1, Tbx-5, Tbx-20, MLC-2a, MLC-2v, α-MHC, cTnI and cTnT) in murine ES and iPS cells. Fasudil-induced cardiac progenitor (Mesp-1 expressing) cells were infused into a murine MI model. They engrafted into the peri-infarct and infarct regions and preserved left ventricular function. These findings provide new insights into the signaling required for ES cell differentiation into hematopoietic as well as cardiac lineages and suggest that ROCK inhibitors are useful in directing iPS cell differentiation into cardiac progenitor cells for cell therapy of cardiovascular diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Inhibition of Rho-associated kinases disturbs the collective cell migration of stratified TE-10 cells

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    Taro Mikami

    2015-01-01

    Full Text Available BACKGROUND: The collective cell migration of stratified epithelial cells is considered to be an important phenomenon in wound healing, development, and cancer invasion; however, little is known about the mechanisms involved. Furthermore, whereas Rho family proteins, including RhoA, play important roles in cell migration, the exact role of Rho-associated coiled coil-containing protein kinases (ROCKs in cell migration is controversial and might be cell-type dependent. Here, we report the development of a novel modified scratch assay that was used to observe the collective cell migration of stratified TE-10 cells derived from a human esophageal cancer specimen. RESULTS: Desmosomes were found between the TE-10 cells and microvilli of the surface of the cell sheet. The leading edge of cells in the cell sheet formed a simple layer and moved forward regularly; these rows were followed by the stratified epithelium. ROCK inhibitors and ROCK small interfering RNAs (siRNAs disturbed not only the collective migration of the leading edge of this cell sheet, but also the stratified layer in the rear. In contrast, RhoA siRNA treatment resulted in more rapid migration of the leading rows and disturbed movement of the stratified portion. CONCLUSIONS: The data presented in this study suggest that ROCKs play an important role in mediating the collective migration of TE-10 cell sheets. In addition, differences between the effects of siRNAs targeting either RhoA or ROCKs suggested that distinct mechanisms regulate the collective cell migration in the simple epithelium of the wound edge versus the stratified layer of the epithelium.

  14. Rho-associated kinase activity is required for proper morphogenesis of the inner cell mass in the mouse blastocyst.

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    Laeno, Arlene May A; Tamashiro, Dana Ann A; Alarcon, Vernadeth B

    2013-11-01

    The blastocyst consists of the outer layer of trophectoderm and pluripotent inner cell mass (ICM), the precursor of the placenta and fetus, respectively. During blastocyst expansion, the ICM adopts a compact, ovoidal shape, whose proper morphology is crucial for normal embryogenesis. Rho-associated kinase (ROCK), an effector of small GTPase RHO signaling, mediates the diverse cellular processes of morphogenesis, but its role in ICM morphogenesis is unclear. Here, we demonstrate that ROCK is required for cohesion of ICM cells and formation of segregated tissues called primitive endoderm (PrE) and epiblast (Epi) in the ICM of the mouse blastocyst. Blastocyst treatment with ROCK inhibitors Y-27632 and Fasudil caused widening or spreading of the ICM, and intermingling of PrE and Epi. Widening of ICM was independent of trophectoderm because isolated ICMs as well as colonies of mouse embryonic stem cells (mESC) also spread upon Y-27632 treatment. PrE, Epi, and trophectoderm cell numbers were similar between control and treated blastocysts, suggesting that ROCK inhibition affected ICM morphology but not lineage differentiation. Rock1 and Rock2 knockdown via RNA interference in mESC also induced spreading, supporting the conclusion that morphological defects caused by the pharmacological inhibitors were due to ROCK inactivation. When blastocysts were transferred into surrogates, implantation efficiencies were unaffected by ROCK inhibition, but treated blastocysts yielded greater fetal loss. These results show that proper ICM morphology is dependent on ROCK activity and is crucial for fetal development. Our studies have wider implication for improving efficiencies of human assisted reproductive technologies that diminish pregnancy loss and promote successful births.

  15. Rho-associated kinase in the gustatory cortex is involved in conditioned taste aversion memory formation but not in memory retrieval or relearning.

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    Sweetat, Sahar; Rosenblum, Kobi; Lamprecht, Raphael

    2012-01-01

    Rho-associated kinase (ROCK) is intimately involved in cortical neuronal morphogenesis. The present study explores the roles of ROCK in conditioned taste aversion (CTA) memory formation in gustatory cortex (GC) in adult rat. Microinjection of the ROCK inhibitor Y-27632 into the GC 30 min before CTA training or 10 min after the conditioned stimulus (CS) impaired long-term CTA memory (LTM) formation. ROCK inhibitor had no effect on taste aversion when injected before the first LTM test day and did not alter taste aversion on subsequent test days. Microinjection of ROCK inhibitor into GC 30 min before preexposure to the taste CS had no effect on latent inhibition of CTA learning suggesting that ROCK is involved in CS-US association rather than taste learning per se. Cumulatively, these results show that ROCK is needed for normal CTA memory formation but not retrieval, relearning or incidental taste learning. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Dynamic changes in neurexins' alternative splicing: role of Rho-associated protein kinases and relevance to memory formation.

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    Gabriela Rozic

    Full Text Available The three neurexins genes (NRXN1/2/3 encode polymorphic synaptic membrane proteins that are involved in cognitive functioning. Neurexins' selectivity of function is presumably conferred through differential use of 2 promoters and 5 alternative splicing sites (SS#1/2/3/4/5. In day-old rat brain neurons grown in culture, activation (depolarization induces reversible, calcium dependent, repression of NRXN2α SS#3 insert. The effects of depolarization on NRXN1/2/3α splicing and biochemical pathways mediating them were further studied in these neurons. NRXN1/2/3α splicing in the course of memory formation in vivo was also explored, using fear conditioning paradigm in rats in which the animals were trained to associate an aversive stimulus (electrical shock with a neutral context (a tone, resulting in the expression of fear responses to the neutral context.In the cultured neurons depolarization induced, beside NRXN2α SS#3, repression of SS#3 and SS#4 exons in NRXN3α but not NRXN1α. The repressions were mediated by the calcium/protein kinase C/Rho-associated protein kinase (ROCK pathway. Fear conditioning induced significant and transient repressions of the NRXN1/2/3α SS#4 exons in the rat hippocampus. ROCK inhibition prior to training attenuated the behavioral fear response, the NRXN1/2/3α splicing repressions and subsequent recovery and the levels of excitatory (PSD95 and inhibitory (gephyrin synaptic proteins in the hippocampus. No such effects were observed in the prefrontal cortex. Significant correlations existed between the fear response and hippocampal NRXN3α and NRXN2α SS#4 inserts as well as PSD95 protein levels. Hippocampal NRXN1α SS#4 insert and gephyrin levels did not correlate with the behavioral response but were negatively correlated with each other.These results show for the first time dynamic, experience related changes in NRXN1/2/3α alternative splicing in the rat brain and a role for ROCK in them. Specific neurexins

  17. Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho-associated kinase II in spinal cord injury rats

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    You-jiang Min

    2017-01-01

    Full Text Available Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase (ROCK signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan (GV3, Dazhui (GV14, Zusanli (ST36 and Ciliao (BL32 and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the mRNA and protein expression of Rho-A and Rho-associated kinase II (ROCKII of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKII. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKII. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of RhoA and ROCKII. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.

  18. Development of Poly Lactic/Glycolic Acid (PLGA Microspheres for Controlled Release of Rho-Associated Kinase Inhibitor

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    Sho Koda

    2017-01-01

    Full Text Available Purpose. The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA as a drug delivery carrier of Rho kinase (ROCK inhibitor for the treatment of corneal endothelial disease. Method. ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1, and a double emulsion [(W1/O/W2] was formed with dichloromethane (O and polyvinyl alcohol (W2. Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography. PLGA was injected into the anterior chamber or subconjunctiva in rabbit eyes, and ocular complication was evaluated by slitlamp microscope and histological analysis. Results. Y-27632 incorporated PLGA microspheres with different molecular weights, and different composition ratios of lactic acid and glycolic acid were fabricated. A high molecular weight and low content of glycolic acid produced a slower and longer release. The Y-27632 released from PLGA microspheres significantly promoted the cell proliferation of cultured corneal endothelial cells. The injection of PLGA did not induce any evident eye complication. Conclusions. ROCK inhibitor-incorporated PLGA microspheres were fabricated, and the microspheres achieved the sustained release of ROCK inhibitor over 7–10 days in vitro. Our data should encourage researchers to use PLGA microspheres for treating corneal endothelial diseases.

  19. Membrane depolarization-induced RhoA/Rho-associated kinase activation and sustained contraction of rat caudal arterial smooth muscle involves genistein-sensitive tyrosine phosphorylation

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    Mita, Mitsuo; Tanaka, Hitoshi; Yanagihara, Hayato; Nakagawa, Jun-ichi; Hishinuma, Shigeru; Sutherland, Cindy; Walsh, Michael P.; Shoji, Masaru

    2013-01-01

    Rho-associated kinase (ROK) activation plays an important role in K+-induced contraction of rat caudal arterial smooth muscle (Mita et al., Biochem J. 2002; 364: 431–40). The present study investigated a potential role for tyrosine kinase activity in K+-induced RhoA activation and contraction. The non-selective tyrosine kinase inhibitor genistein, but not the src family tyrosine kinase inhibitor PP2, inhibited K+-induced sustained contraction (IC50 = 11.3 ± 2.4 µM). Genistein (10 µM) inhibited the K+-induced increase in myosin light chain (LC20) phosphorylation without affecting the Ca2+ transient. The tyrosine phosphatase inhibitor vanadate induced contraction that was reversed by genistein (IC50 = 6.5 ± 2.3 µM) and the ROK inhibitor Y-27632 (IC50 = 0.27 ± 0.04 µM). Vanadate also increased LC20 phosphorylation in a genistein- and Y-27632-dependent manner. K+ stimulation induced translocation of RhoA to the membrane, which was inhibited by genistein. Phosphorylation of MYPT1 (myosin-targeting subunit of myosin light chain phosphatase) was significantly increased at Thr855 and Thr697 by K+ stimulation in a genistein- and Y-27632-sensitive manner. Finally, K+ stimulation induced genistein-sensitive tyrosine phosphorylation of proteins of ∼55, 70 and 113 kDa. We conclude that a genistein-sensitive tyrosine kinase, activated by the membrane depolarization-induced increase in [Ca2+]i, is involved in the RhoA/ROK activation and sustained contraction induced by K+. Ca2+ sensitization, myosin light chain phosphatase, RhoA, Rho-associated kinase, tyrosine kinase PMID:24133693

  20. A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells

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    Kalcheim Chaya

    2008-10-01

    Full Text Available Abstract Background Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. Results We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Conclusion Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion.

  1. Rho-Kinase/ROCK as a Potential Drug Target for Vitreoretinal Diseases

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    Muneo Yamaguchi

    2017-01-01

    Full Text Available Rho-associated kinase (Rho-kinase/ROCK was originally identified as an effector protein of the G protein Rho. Its involvement in various diseases, particularly cancer and cardiovascular disease, has been elucidated, and ROCK inhibitors have already been applied clinically for cerebral vasospasm and glaucoma. Vitreoretinal diseases including diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinoapthy are still a major cause of blindness. While anti-VEGF therapy has recently been widely used for vitreoretinal disorders due to its efficacy, attention has been drawn to new unmet needs. The importance of ROCK in pathological vitreoretinal conditions has also been elucidated and is attracting attention as a potential therapeutic target. ROCK is involved in angiogenesis and hyperpermeability and also in the pathogenesis of various pathologies such as inflammation and fibrosis. It has been expected that ROCK inhibitors will become new molecular target drugs for vitreoretinal diseases. This review summarizes the recent progress on the mechanisms of action of ROCK and their applications in disease treatment.

  2. The selectivity and promiscuity of brain-neuroregenerative inhibitors between ROCK1 and ROCK2 isoforms: An integration of SB-QSSR modelling, QM/MM analysis and in vitro kinase assay.

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    Zhu, L; Yang, Y; Lu, X

    2016-01-01

    The Rho-associated kinases (ROCKs) have long been recognized as an attractive therapeutic target for various neurological diseases; selective inhibition of ROCK1 and ROCK2 isoforms would result in distinct biological effects on neurogenesis, neuroplasticity and neuroregeneration after brain surgery and traumatic brain injury. However, the discovery and design of isoform-selective inhibitors remain a great challenge due to the high conservation and similarity between the kinase domains of ROCK1 and ROCK2. Here, a structure-based quantitative structure-selectivity relationship (SB-QSSR) approach was used to correlate experimentally measured selectivity with the difference in inhibitor binding to the two kinase isoforms. The resulting regression models were examined rigorously through both internal cross-validation and external blind validation; a nonlinear predictor was found to have high fitting stability and strong generalization ability, which was then employed to perform virtual screening against a structurally diverse, drug-like compound library. Consequently, five and seven hits were identified as promising candidates of 1-o-2 and 2-o-1 selective inhibitors, respectively, from which seven purchasable compounds were tested in vitro using a standard kinase assay protocol to determine their inhibitory activity against and selectivity between ROCK1 and ROCK2. The structural basis, energetic property and biological implication underlying inhibitor selectivity and promiscuity were also investigated systematically using a hybrid quantum mechanics/molecular mechanics (QM/MM) scheme.

  3. Phosphoryl transfer is not rate-limiting for the ROCK I-catalyzed kinase reaction.

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    Futer, Olga; Saadat, Ahmad R; Doran, John D; Raybuck, Scott A; Pazhanisamy, S

    2006-06-27

    Rho-associated coiled-coil kinase, ROCK, is implicated in Rho-mediated cell adhesion and smooth muscle contraction. Animal models suggest that the inhibition of ROCK can ameliorate conditions, such as vasospasm, hypertension, and inflammation. As part of our effort to design novel inhibitors of ROCK, we investigated the kinetic mechanism of ROCK I. Steady-state bisubstrate kinetics, inhibition kinetics, isotope partition analysis, viscosity effects, and presteady-state kinetics were used to explore the kinetic mechanism. Plots of reciprocals of initial rates obtained in the presence of nonhydrolyzable ATP analogues and the small molecule inhibitor of ROCK, Y-27632, against the reciprocals of the peptide concentrations yielded parallel lines (uncompetitive pattern). This pattern is indicative of an ordered binding mechanism, with the peptide adding first. The staurosporine analogue K252a, however, gave a noncompetitive pattern. When a pulse of (33)P-gamma-ATP mixed with ROCK was chased with excess unlabeled ATP and peptide, 0.66 enzyme equivalent of (33)P-phosphate was incorporated into the product in the first turnover. The presence of ATPase activity coupled with the isotope partition data is a clear evidence for the existence of a viable [E-ATP] complex in the kinase reaction and implicates a random binding mechanism. The k(cat)/K(m) parameters were fully sensitive to viscosity (viscosity effects of 1.4 +/- 0.2 and 0.9 +/- 0.3 for ATP and peptide 5, respectively), and therefore, the barriers to dissociation of either substrate are higher than the barrier for the phosphoryl transfer step. As a consequence, not all the binding steps are at fast equilibrium. The observation of a burst in presteady-state kinetics (k(b) = 10.2 +/- 2.1 s(-)(1)) and the viscosity effect on k(cat) of 1.3 +/- 0.2 characterize the phosphoryl transfer step to be fast and the release of product and/or the enzyme isomerization step accompanying it as rate-limiting at V(max) conditions. From

  4. Regulation of ROCK Activity in Cancer

    DEFF Research Database (Denmark)

    Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

    2013-01-01

    , these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.......Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key...... regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active...

  5. Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway

    NARCIS (Netherlands)

    Wang, Siyuan; Chen, Cheng; Su, Ke; Zha, Dongqing; Liang, Wei; Hillebrands, J L; van Goor, Harry; Ding, Guohua

    2016-01-01

    Aims In the present study, we have evaluated the effect of angiotensin II (Ang II) on actin cytoskeleton reorganization and myosin light-chain (MLC) phosphorylation in podocytes to demonstrate whether the Rho/Rho-associated coiled kinase (ROCK) pathway is involved podocyte injury. Methods Eighteen

  6. Regulation of ROCK Activity in Cancer

    Science.gov (United States)

    Morgan-Fisher, Marie; Wewer, Ulla M.

    2013-01-01

    Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)–loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112

  7. ROCK and PRK-2 Mediate the Inhibitory Effect of Y-27632 on Polyglutamine Aggregation

    Science.gov (United States)

    Shao, Jieya; Welch, William J.; Diamond, Marc I.

    2009-01-01

    Polyglutamine expansion in huntingtin (Htt) and the androgen receptor (AR) causes untreatable neurodegenerative diseases. Y-27632, a therapeutic lead, reduces Htt and AR aggregation in cultured cells, and Htt-induced neurodegeneration in Drosophila. Y-27632 inhibits both Rho-associated kinases ROCK and PRK-2, making its precise intracellular target uncertain. Over-expression of either kinase increases Htt and AR aggregation. Three ROCK inhibitors (Y-27632, H-1077, HA-1152), and a specific ROCK inhibitory peptide reduce polyglutamine protein aggregation, as does knockdown of ROCK or PRK-2 by RNAi. RNAi also indicates that each kinase is required for the inhibitory effects of Y-27632 to manifest fully. These two actin regulatory kinases are thus involved in polyglutamine aggregation, and their simultaneous inhibition may be an important therapeutic goal. PMID:18423405

  8. Rho Kinase (ROCK) collaborates with Pak to Regulate Actin Polymerization and Contraction in Airway Smooth Muscle.

    Science.gov (United States)

    Zhang, Wenwu; Bhetwal, Bhupal P; Gunst, Susan J

    2018-05-10

    The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation. We find that ROCK regulates airway smooth muscle contraction by activating the serine-threonine kinase Pak, which mediates the activation of Cdc42 and Neuronal-Wiskott-Aldrich Syndrome protein (N-WASp). N-WASP transmits signals from cdc42 to the Arp2/3 complex for the nucleation of actin filaments. These results demonstrate a novel molecular function for ROCK in the regulation of Pak and cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle. Rho kinase (ROCK), a RhoA GTPase effector, can regulate the contraction of airway and other smooth muscle tissues. In some tissues, ROCK can inhibit myosin regulatory light chain (RLC) phosphatase, which increases the phosphorylation of myosin RLC and promotes smooth muscle contraction. ROCK can also regulate cell motility and migration by affecting F-actin dynamics. Actin polymerization is stimulated by contractile agonists in airway smooth muscle tissues and is required for contractile tension development in addition to myosin RLC phosphorylation. We investigated the mechanisms by which ROCK regulates the contractility of tracheal smooth muscle tissues by expressing a kinase inactive mutant of ROCK, ROCK-K121G, in the tissues or by treating them with the ROCK inhibitor, H-1152P. Our results show no role for ROCK in the regulation of non-muscle or smooth muscle myosin RLC phosphorylation during contractile stimulation in this tissue

  9. ROCK1 as a novel prognostic marker in vulvar cancer

    DEFF Research Database (Denmark)

    Akagi, Erica M; Lavorato-Rocha, André M; Maia, Beatriz de Melo

    2014-01-01

    infection, but most cases develop in women aged over 50 years through poorly understood genetic mechanisms. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been implicated in many cellular processes, but its function in vulvar cancer has never been examined. In this study, we aimed...... to determine the prognostic value of ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC). METHODS: ROCK1 expression levels were measured in 16 vulvar tumour samples and adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by immunohistochemistry (IHC) to confirm...... the involvement of ROCK1 in the disease. The molecular and pathological results were correlated with the clinical data of the patients. Sixteen fresh VSCC samples were analyzed by array-based comparative genomic hybridization (aCGH). RESULTS: In each pair of samples, ROCK1 levels were higher by qRT-PCR in normal...

  10. The ROCK isoforms differentially regulate the morphological characteristics of carcinoma cells.

    Science.gov (United States)

    Jerrell, Rachel J; Leih, Mitchell J; Parekh, Aron

    2017-06-26

    Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between 2 modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes. Here, we found that ROCK1 and ROCK2 differentially regulate carcinoma cell morphology resulting in intermediate phenotypes that share some mesenchymal and amoeboid characteristics. These findings suggest that the ROCK isoforms play unique roles in the phenotypic plasticity of mesenchymal carcinoma cells which may have therapeutic implications.

  11. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Jie Hong

    Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  12. ROCK inhibition with Y27632 promotes the proliferation and cell cycle progression of cultured astrocyte from spinal cord.

    Science.gov (United States)

    Yu, Zhiyuan; Liu, Miao; Fu, Peicai; Xie, Minjie; Wang, Wei; Luo, Xiang

    2012-12-01

    Rho-associated Kinase (ROCK) has been identified as an important regulator of proliferation and cell cycle progression in a number of cell types. Although its effects on astrocyte proliferation have not been well characterized, ROCK has been reported to play important roles in gap junction formation, morphology, and migration of astrocytes. In the present study, our aim was to investigate the effect of ROCK inhibition by [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride] (Y27632) on proliferation and DNA synthesis in cultured astrocytes from rat spinal cord and the possible mechanism involved. Western blots showed that treatment of astrocytes with Y27632 increased their expression of cyclin D1, CDK4, and cyclin E, thereby causing cell cycle progression. Furthermore, Y27632-induced astrocyte proliferation was mediated through the extracellular-signal-regulated kinase signaling cascade. These results indicate the importance of ROCK in astrocyte proliferation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Integrin cytoplasmic domain-associated protein-1 (ICAP-1) interacts with the ROCK-I kinase at the plasma membrane

    NARCIS (Netherlands)

    Stroeken, Peter J. M.; Alvarez, Belén; van Rheenen, Jacco; Wijnands, Yvonne M.; Geerts, Dirk; Jalink, Kees; Roos, Ed

    2006-01-01

    The integrin cytoplasmic domain-associated protein-1 (ICAP-1) binds via its C-terminal PTB (phosphotyrosine-binding) domain to the cytoplasmic tails of beta1 but not other integrins. Using the yeast two-hybrid assay, we found that ICAP-1 binds the ROCK-I kinase, an effector of the RhoA GTPase. By

  14. ROCK as a therapeutic target for ischemic stroke.

    Science.gov (United States)

    Sladojevic, Nikola; Yu, Brian; Liao, James K

    2017-12-01

    Stroke is a major cause of disability and the fifth leading cause of death. Currently, the only approved acute medical treatment of ischemic stroke is tissue plasminogen activator (tPA), but its effectiveness is greatly predicated upon early administration of the drug. There is, therefore, an urgent need to find new therapeutic options for acute stroke. Areas covered: In this review, we summarize the role of Rho-associated coiled-coil containing kinase (ROCK) and its potential as a therapeutic target in stroke pathophysiology. ROCK is a major regulator of cell contractility, motility, and proliferation. Many of these ROCK-mediated processes in endothelial cells, vascular smooth muscle cells, pericytes, astrocytes, glia, neurons, leukocytes, and platelets are important in stroke pathophysiology, and the inhibition of such processes could improve stroke outcome. Expert commentary: ROCK is a potential therapeutic target for cardiovascular disease and ROCK inhibitors have already been approved for human use in Japan and China for the treatment of acute stroke. Further studies are needed to determine the role of ROCK isoforms in the pathophysiology of cerebral ischemia and whether there are further therapeutic benefits with selective ROCK inhibitors.

  15. Opportunities to Target Specific Contractile Abnormalities with Smooth Muscle Protein Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Annegret Ulke-Lemée

    2010-05-01

    Full Text Available Smooth muscle is a major component of most hollow organ systems (e.g., airways, vasculature, bladder and gut/gastrointestine; therefore, the coordinated regulation of contraction is a key property of smooth muscle. When smooth muscle functions normally, it contributes to general health and wellness, but its dysfunction is associated with morbidity and mortality. Rho-associated protein kinase (ROCK is central to calcium-independent, actomyosin-mediated contractile force generation in the vasculature, thereby playing a role in smooth muscle contraction, cell motility and adhesion. Recent evidence supports an important role for ROCK in the increased vasoconstriction and remodeling observed in various models of hypertension. This review will provide a commentary on the development of specific ROCK inhibitors and their clinical application. Fasudil will be discussed as an example of bench-to-bedside development of a clinical therapeutic that is used to treat conditions of vascular hypercontractility. Due to the wide spectrum of biological processes regulated by ROCK, many additional clinical indications might also benefit from ROCK inhibition. Apart from the importance of ROCK in smooth muscle contraction, a variety of other protein kinases are known to play similar roles in regulating contractile force. The zipper-interacting protein kinase (ZIPK and integrin-linked kinase (ILK are two well-described regulators of contraction. The relative contribution of each kinase to contraction depends on the muscle bed as well as hormonal and neuronal stimulation. Unfortunately, specific inhibitors for ZIPK and ILK are still in the development phase, but the success of fasudil suggests that inhibitors for these other kinases may also have valuable clinical applications. Notably, the directed inhibition of ZIPK with a pseudosubstrate molecule shows unexpected effects on the contractility of gastrointestinal smooth muscle.

  16. The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis

    Science.gov (United States)

    Knipe, Rachel S.; Tager, Andrew M.

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, short median survival, and limited therapeutic options, creating great need for new pharmacologic therapies. IPF is thought to result from repetitive environmental injury to the lung epithelium, in the context of aberrant host wound healing responses. Tissue responses to injury fundamentally involve reorganization of the actin cytoskeleton of participating cells, including epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament assembly and actomyosin contraction are directed by the Rho-associated coiled-coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and ROCK2). As would therefore be expected, lung ROCK activation has been demonstrated in humans with IPF and in animal models of this disease. ROCK inhibitors can prevent fibrosis in these models, and more importantly, induce the regression of already established fibrosis. Here we review ROCK structure and function, upstream activators and downstream targets of ROCKs in pulmonary fibrosis, contributions of ROCKs to profibrotic cellular responses to lung injury, ROCK inhibitors and their efficacy in animal models of pulmonary fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation is required for multiple profibrotic responses, in the lung and multiple other organs, suggesting ROCK participation in fundamental pathways that contribute to the pathogenesis of a broad array of fibrotic diseases. Multiple lines of evidence therefore indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond. PMID:25395505

  17. Rho-associated protein kinase regulates subcellular localisation of Angiomotin and Hippo-signalling during preimplantation mouse embryo development

    Czech Academy of Sciences Publication Activity Database

    Mihajlović, A. I.; Bruce, Alexander

    2016-01-01

    Roč. 33, č. 3 (2016), s. 381-390 ISSN 1472-6483 Grant - others:GA ČR(CZ) GA13-03295S; GA JU(CZ) 004/2015/P Institutional support: RVO:60077344 Keywords : Angiomotin * Hippo-signalling * polarization Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.249, year: 2016 http://www.sciencedirect.com/science/article/pii/S1472648316304047

  18. A crucial role of ROCK for alleviation of senescence-associated phenotype.

    Science.gov (United States)

    Park, Joon Tae; Kang, Hyun Tae; Park, Chi Hyun; Lee, Young-Sam; Cho, Kyung A; Park, Sang Chul

    2018-06-01

    In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. We found that ROCK inhibition induced the functional recovery of the mitochondria as well as the metabolic reprogramming, which are two salient features that are altered in normal aging cells. Moreover, microarray analysis revealed that the up-regulated pathway upon ROCK inhibition is enriched for chromatin remodeling genes, which may play an important role in the alleviation of senescence-associated cell cycle arrest. Indeed, ROCK inhibition induced cellular proliferation, concomitant with the amelioration of senescent phenotype. Furthermore, the restorative effect by ROCK inhibition was observed in vivo as evidenced by the facilitated cutaneous wound healing. Taken together, our data indicate that ROCK inhibition might be utilized to ameliorate normal aging process and to treat age-related disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Kang, Hyun Tae; Park, Joon Tae; Choi, Kobong; Choi, Hyo Jei Claudia; Jung, Chul Won; Kim, Gyu Ree; Lee, Young-Sam; Park, Sang Chul

    2017-06-01

    Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent. To elucidate the underlying mechanism of ROCK in regulating ROS levels, we performed a yeast two-hybrid screen and discovered that ROCK1 interacts with Rac1b. ROCK activation phosphorylated Rac1b at Ser71 and increased ROS levels by facilitating the interaction between Rac1b and cytochrome c. Conversely, ROCK inactivation with Y-27632 abolished their interaction, concomitant with ROS reduction. Additionally, ROCK activation resulted in mitochondrial dysfunction, whereas ROCK inactivation with Y-27632 induced the recovery of mitochondrial function. Furthermore, a reduction in the frequency of abnormal nuclear morphology and DNA double-strand breaks was observed along with decreased ROS levels. Thus, our study reveals a novel mechanism through which alleviation of the HGPS phenotype is mediated by the recovery of mitochondrial function upon ROCK inactivation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. ROCK and RHO Playlist for Preimplantation Development: Streaming to HIPPO Pathway and Apicobasal Polarity in the First Cell Differentiation.

    Science.gov (United States)

    Alarcon, Vernadeth B; Marikawa, Yusuke

    2018-01-01

    In placental mammalian development, the first cell differentiation produces two distinct lineages that emerge according to their position within the embryo: the trophectoderm (TE, placenta precursor) differentiates in the surface, while the inner cell mass (ICM, fetal body precursor) forms inside. Here, we discuss how such position-dependent lineage specifications are regulated by the RHOA subfamily of small GTPases and RHO-associated coiled-coil kinases (ROCK). Recent studies in mouse show that activities of RHO/ROCK are required to promote TE differentiation and to concomitantly suppress ICM formation. RHO/ROCK operate through the HIPPO signaling pathway, whose cell position-specific modulation is central to establishing unique gene expression profiles that confer cell fate. In particular, activities of RHO/ROCK are essential in outside cells to promote nuclear localization of transcriptional co-activators YAP/TAZ, the downstream effectors of HIPPO signaling. Nuclear localization of YAP/TAZ depends on the formation of apicobasal polarity in outside cells, which requires activities of RHO/ROCK. We propose models of how RHO/ROCK regulate lineage specification and lay out challenges for future investigations to deepen our understanding of the roles of RHO/ROCK in preimplantation development. Finally, as RHO/ROCK may be inhibited by certain pharmacological agents, we discuss their potential impact on human preimplantation development in relation to fertility preservation in women.

  1. Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of glaucoma.

    Science.gov (United States)

    Honjo, Megumi; Tanihara, Hidenobu

    2018-03-01

    Rho-associated protein kinase (ROCK), a ubiquitously expressed signaling messenger and downstream effector of Rho, is activated by several bioactive factors in the aqueous humor (AH). Rho-ROCK signaling regulates a wide spectrum of fundamental cellular events, including cell adhesion, motility, proliferation, differentiation, and apoptosis. Previous studies, including our own, found that ROCK inhibitor lowers intraocular pressure (IOP) via a direct effect on the conventional AH outflow pathway, by regulation of contractile properties, fibrotic activity, and permeability of the trabecular meshwork (TM) and Schlemm's canal (SC) tissues, influencing extracellular matrix (ECM) production. Recently, a novel ROCK inhibitor, ripasudil, has been introduced in Japan. Other ROCK inhibitors are now in clinical trials as new IOP-lowering drugs for glaucoma patients. To date, ripasudil, administered together with other glaucoma medications, has proved safe and efficient in lowering IOP as well as additional effects such as prostaglandin analogs, beta-blockers, and carbonic anhydrase inhibitors, all of which help lower IOP by different mechanisms. In addition, we found that long-term treatment with ripasudil exerted an additional IOP-lowering effect, especially in eyes with high IOP, suggesting that late-onset remodeling of the ECM in glaucomatous eyes may elicit mild and delayed changes in IOP levels. ROCK inhibitors have also shown several additional effects, including increased retinal blood flow, direct protection of neurons against various types of stress, and regulation of wound healing; these benefits may potentially be useful in glaucoma treatment.

  2. ROCK inhibition abolishes the establishment of the aquiferous system in Ephydatia muelleri (Porifera, Demospongiae).

    Science.gov (United States)

    Schenkelaars, Quentin; Quintero, Omar; Hall, Chelsea; Fierro-Constain, Laura; Renard, Emmanuelle; Borchiellini, Carole; Hill, April L

    2016-04-15

    The Rho associated coiled-coil protein kinase (ROCK) plays crucial roles in development across bilaterian animals. The fact that the Rho/Rock pathway is required to initiate epithelial morphogenesis and thus to establish body plans in bilaterians makes this conserved signaling pathway key for studying the molecular mechanisms that may control early development of basally branching metazoans. The purpose of this study was to evaluate whether or not the main components of this signaling pathway exist in sponges, and if present, to investigate the possible role of the regulatory network in an early branching non-bilaterian species by evaluating ROCK function during Ephydatia muelleri development. Molecular phylogenetic analyses and protein domain predictions revealed the existence of Rho/Rock components in all studied poriferan lineages. Binding assays revealed that both Y-27632 and GSK429286A are capable of inhibiting Em-ROCK activity in vitro. Treatment with both drugs leads to impairment of growth and formation of the basal pinacoderm layer in the developing sponge. Furthermore, inhibition of Em-Rock prevents the establishment of a functional aquiferous system, including the absence of an osculum. In contrast, no effect of ROCK inhibition was observed in juvenile sponges that already possess a fully developed and functional aquiferous system. Thus, the Rho/Rock pathway appears to be essential for the proper development of the freshwater sponge, and may play a role in various cell behaviors (e.g. cell proliferation, cell adhesion and cell motility). Taken together, these data are consistent with an ancestral function of Rho/Rock signaling in playing roles in early developmental processes and may provide a new framework to study the interaction between Wnt signaling and the Rho/Rock pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Rho/ROCK signaling in regulation of corneal epithelial cell cycle progression.

    Science.gov (United States)

    Chen, Jian; Guerriero, Emily; Lathrop, Kira; SundarRaj, Nirmala

    2008-01-01

    The authors' previous study showed that the expression of a Rho-associated serine/threonine kinase (ROCK) is regulated during cell cycle progression in corneal epithelial cells. The present study was conducted to determine whether and how Rho/ROCK signaling regulates cell cycle progression. Rabbit corneal epithelial cells (RCECs) in culture were arrested in the G(0) phase of the cell cycle by serum deprivation and then allowed to re-enter the cell cycle in the presence or absence of the ROCK inhibitor (Y27632) in serum-supplemented medium. The number of cells in the S phase, the relative levels of specific cyclins and CDKs and their intracellular distribution, and the relative levels of mRNAs were determined by BrdU labeling, Western blot and immunocytochemical analyses, and real-time RT-PCR, respectively. ROCK inhibition delayed the progression of G(1) to S phase and led to a decrease in the number of RCECs entering the S phase between 12 and 24 hours from 31.5% +/- 4.5% to 8.1% +/- 2.6%. During the cell cycle progression, protein and mRNA levels of cyclin-D1 and -D3 and cyclin-dependent kinases CDK4 and CDK6 were significantly lower, whereas the protein levels of the CDK inhibitor p27(Kip1) were higher in ROCK-inhibited cells. Intracellular mRNA or protein levels of cyclin-E and protein levels of CDK2 were not significantly affected, but their nuclear translocation was delayed by ROCK inhibition. ROCK signaling is involved in cell cycle progression in RCECs, possibly by upregulation of cyclin-D1 and -D3 and CDK4, -6, and -2; nuclear translocation of CDK2 and cyclin-E; and downregulation of p27(Kip1).

  4. Oxidative stress, caspase-3 activation and cleavage of ROCK-1 play an essential role in MeHg-induced cell death in primary astroglial cells.

    Science.gov (United States)

    Dos Santos, Alessandra Antunes; López-Granero, Caridad; Farina, Marcelo; Rocha, João B T; Bowman, Aaron B; Aschner, Michael

    2018-03-01

    Methylmercury is a toxic environmental contaminant that elicits significant toxicity in humans. The central nervous system is the primary target of toxicity, and is particularly vulnerable during development. Rho-associated protein kinase 1 (ROCK-1) is a major downstream effector of the small GTPase RhoA and a direct substrate of caspase-3. The activation of ROCK-1 is necessary for membrane blebbing during apoptosis. In this work, we examined whether MeHg could affect the RhoA/ROCK-1 signaling pathway in primary cultures of mouse astrocytes. Exposure of cells with 10 μM MeHg decreased cellular viability after 24 h of incubation. This reduction in viability was preceded by a significant increase in intracellular and mitochondrial reactive oxygen species levels, as well as a reduced NAD + /NADH ratio. MeHg also induced an increase in mitochondrial-dependent caspase-9 and caspase-3, while the levels of RhoA protein expression were reduced or unchanged. We further found that MeHg induced ROCK-1 cleavage/activation and promoted LIMK1 and MYPT1 phosphorylation, both of which are the best characterized ROCK-1 downstream targets. Inhibiting ROCK-1 and caspases activation attenuated the MeHg-induced cell death. Collectively, these findings are the first to show that astrocytes exposed to MeHg showed increased cleavage/activation of ROCK-1, which was independent of the small GTPase RhoA. Copyright © 2018. Published by Elsevier Ltd.

  5. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK.

    Directory of Open Access Journals (Sweden)

    Steve Pedrini

    2005-01-01

    Full Text Available Statins are widely used cholesterol-lowering drugs that act by inhibiting HMGCoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent evidence suggests that statin use may be associated with a decreased risk for Alzheimer disease, although the mechanisms underlying this apparent risk reduction are poorly understood. One popular hypothesis for statin action is related to the drugs' ability to activate alpha-secretase-type shedding of the alpha-secretase-cleaved soluble Alzheimer amyloid precursor protein ectodomain (sAPP(alpha. Statins also inhibit the isoprenoid pathway, thereby modulating the activities of the Rho family of small GTPases-Rho A, B, and C-as well as the activities of Rac and cdc42. Rho proteins, in turn, exert many of their effects via Rho-associated protein kinases (ROCKs. Several cell-surface molecules are substrates for activated alpha-secretase-type ectodomain shedding, and regulation of shedding typically occurs via activation of protein kinase C or extracellular-signal-regulated protein kinases, or via inactivation of protein phosphatase 1 or 2A. However, the possibility that these enzymes play a role in statin-stimulated shedding has been excluded, leading us to investigate whether the Rho/ROCK1 protein phosphorylation pathway might be involved.We found that both atorvastatin and simvastatin stimulated sAPP(alpha shedding from a neuroblastoma cell line via a subcellular mechanism apparently located upstream of endocytosis. A farnesyl transferase inhibitor also increased sAPP(alpha shedding, as did a dominant negative form of ROCK1. Most conclusively, a constitutively active ROCK1 molecule inhibited statin-stimulated sAPP(alpha shedding.Together, these data suggest that statins exert their effects on shedding of sAPP(alpha from cultured cells, at least in part, by modulation of the isoprenoid pathway and ROCK1.

  6. Substrate Stiffness Influences Doxorubicin-Induced p53 Activation via ROCK2 Expression

    Directory of Open Access Journals (Sweden)

    Takahiro Ebata

    2017-01-01

    Full Text Available The physical properties of the extracellular matrix (ECM, such as stiffness, are involved in the determination of the characteristics of cancer cells, including chemotherapy sensitivity. Resistance to chemotherapy is often linked to dysfunction of tumor suppressor p53; however, it remains elusive whether the ECM microenvironment interferes with p53 activation in cancer cells. Here, we show that, in MCF-7 breast cancer cells, extracellular stiffness influences p53 activation induced by the antitumor drug doxorubicin. Cell growth inhibition by doxorubicin was increased in response to ECM rigidity in a p53-dependent manner. The expression of Rho-associated coiled coil-containing protein kinase (ROCK 2, which induces the activation of myosin II, was significantly higher when cells were cultured on stiffer ECM substrates. Knockdown of ROCK2 expression or pharmacological inhibition of ROCK decreased doxorubicin-induced p53 activation. Our results suggest that a soft ECM causes downregulation of ROCK2 expression, which drives resistance to chemotherapy by repressing p53 activation.

  7. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease.

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    Mei Li

    Full Text Available Huntington disease (HD is an inherited neurodegenerative disease that affects multiple brain regions. It is caused by an expanded polyglutamine tract in huntingtin (Htt. The development of therapies for HD and other neurodegenerative diseases has been hampered by multiple factors, including the lack of clear therapeutic targets, and the cost and complexity of testing lead compounds in vivo. The R6/2 HD mouse model is widely used for pre-clinical trials because of its progressive and robust neural dysfunction, which includes retinal degeneration. Profilin-1 is a Htt binding protein that inhibits Htt aggregation. Its binding to Htt is regulated by the rho-associated kinase (ROCK, which phosphorylates profilin at Ser-137. ROCK is thus a therapeutic target in HD. The ROCK inhibitor Y-27632 reduces Htt toxicity in fly and mouse models. Here we characterized the progressive retinopathy of R6/2 mice between 6-19 weeks of age to determine an optimal treatment window. We then tested a clinically approved ROCK inhibitor, HA-1077, administered intravitreally via liposome-mediated drug delivery. HA-1077 increased photopic and flicker ERG response amplitudes in R6/2 mice, but not in wild-type littermate controls. By targeting ROCK with a new inhibitor, and testing its effects in a novel in vivo model, these results validate the in vivo efficacy of a therapeutic candidate, and establish the feasibility of using the retina as a readout for CNS function in models of neurodegenerative disease.

  8. Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells.

    Science.gov (United States)

    Diep, Duy Trong Vien; Hong, Kyungki; Khun, Triyeng; Zheng, Mei; Ul-Haq, Asad; Jun, Hee-Sook; Kim, Young-Bum; Chun, Kwang-Hoon

    2018-02-06

    Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4. Interestingly, adipogenesis was blocked by KD025 during days 1~3 of differentiation; after differentiation terminated, lipid accumulation was unaffected. Clonal expansion occurred normally in KD025-treated cells. These results suggest that KD025 could function during the intermediate stage after clonal expansion. Data from depletion of ROCKs showed that KD025 suppressed cell differentiation partially independent of ROCK's activity. Furthermore, no further loss of actin stress fibers emerged in KD025-treated cells during and after differentiation compared to control cells. These results indicate that in contrast to the pro-adipogenic effect of pan-inhibitors, KD025 suppresses adipogenesis in 3T3-L1 cells by regulating key pro-adipogenic factors. This outcome further implies that KD025 could be a potential anti-adipogenic/obesity agent.

  9. In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5.

    Science.gov (United States)

    Arya, Hemant; Syed, Safiulla Basha; Singh, Sorokhaibam Sureshkumar; Ampasala, Dinakar R; Coumar, Mohane Selvaraj

    2017-06-16

    Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5). Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the plant to interact with the anti-hypertensive drug targets with good glide score. In addition, they formed H-bond interactions with the key residues Met156/Met157 of ROCK I/ROCK II and Gln817 of PDE5. Further, molecular dynamics (MD) simulation of protein-ligand complexes suggest that H-bond interactions between acteoside/osmanthuside β6 and Met156/Met157 (ROCK I/ROCK II), acteoside and Gln817 (PDE5) were stable. The present investigation suggests that the anti-hypertensive activity of the plant is due to the interaction of acteoside and osmanthuside β6 with ROCK and PDE5 drug targets. The identified molecular mode of binding of the plant constituents could help to design new drugs to treat hypertension.

  10. Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability

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    Lijun Du

    2016-01-01

    Full Text Available The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn’s disease (CD, ulcerative colitis (UC, celiac disease, and irritable bowel syndrome (IBS. Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK- and myosin light chain kinase- (MLCK- mediated pathways are involved in the regulation of intestinal permeability. With this perspective, we aim to summarize the current state of knowledge regarding the role of inflammation and ROCK-/MLCK-mediated pathways leading to intestinal hyperpermeability in gastrointestinal disorders. In the near future, it may be possible to specifically target these specific pathways to develop novel therapies for gastrointestinal disorders associated with increased gut permeability.

  11. ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.

    Science.gov (United States)

    Rothschild, Pierre-Raphaël; Salah, Sawsen; Berdugo, Marianne; Gélizé, Emmanuelle; Delaunay, Kimberley; Naud, Marie-Christine; Klein, Christophe; Moulin, Alexandre; Savoldelli, Michèle; Bergin, Ciara; Jeanny, Jean-Claude; Jonet, Laurent; Arsenijevic, Yvan; Behar-Cohen, Francine; Crisanti, Patricia

    2017-08-18

    In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

  12. Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

    Directory of Open Access Journals (Sweden)

    John Meshki

    Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

  13. Incarvine C suppresses proliferation and vasculogenic mimicry of hepatocellular carcinoma cells via targeting ROCK inhibition

    International Nuclear Information System (INIS)

    Zhang, Ji-Gang; Zhang, Dan-Dan; Wu, Xin; Wang, Yu-Zhu; Gu, Sheng-Ying; Zhu, Guan-Hua; Li, Xiao-Yu; Li, Qin; Liu, Gao-Lin

    2015-01-01

    Studies have described vasculogenic mimicry (VM) as an alternative circulatory system to blood vessels in multiple malignant tumor types, including hepatocellular carcinoma (HCC). In the current study, we aimed to seek novel and more efficient treatment strategies by targeting VM and explore the underlying mechanisms in HCC cells. Cell counting kit-8 (CCK-8) assay and colony survival assay were performed to explore the inhibitory effect of incarvine C (IVC) on human cancer cell proliferation. Flow cytometry was performed to analyze the cell cycle distribution after DNA staining and cell apoptosis by the Annexin V-PE and 7-AAD assay. The effect of IVC on Rho-associated, coiled-coil-containing protein kinase (ROCK) was determined by western blotting and stress fiber formation assay. The inhibitory role of IVC on MHCC97H cell VM formation was determined by formation of tubular network structures on Matrigel in vitro, real time-qPCR, confocal microscopy and western blotting techniques. We explored an anti-metastatic HCC agent, IVC, derived from traditional Chinese medicinal herbs, and found that IVC dose-dependently inhibited the growth of MHCC97H cells. IVC induced MHCC97H cell cycle arrest at G1 transition, which was associated with cyclin-dependent kinase 2 (CDK-2)/cyclin-E1 degradation and p21/p53 up-regulation. In addition, IVC induced apoptotic death of MHCC97H cells. Furthermore, IVC strongly suppressed the phosphorylation of the ROCK substrate myosin phosphatase target subunit-1 (MYPT-1) and ROCK-mediated actin fiber formation. Finally, IVC inhibited cell-dominant tube formation in vitro, which was accompanied with the down-regulation of VM-key factors as detected by real time-qPCR and immunofluorescence. Taken together, the effective inhibitory effect of IVC on MHCC97H cell proliferation and neovascularization was associated with ROCK inhibition, suggesting that IVC may be a new potential drug candidate for the treatment of HCC

  14. Rho kinase inhibitor fasudil mitigates high-cholesterol diet-induced hypercholesterolemia and vascular damage.

    Science.gov (United States)

    Abdali, Nibrass Taher; Yaseen, Awny H; Said, Eman; Ibrahim, Tarek M

    2017-04-01

    The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2.5 mg/kg/day) starting from the ninth week for further 4 weeks with interruption of the cholesterol-rich chow. Biochemical assessment of serum cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and myocardial oxidative/antioxidant biomarkers malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), besides biochemical assessment of serum nitric oxide (NO), creatine kinase (CK), and lactate dehydrogenase (LDH) activities and serum total antioxidant capacity (TAC), was conducted. Serum vascular cell adhesion molecule 1 (VCAM-1) and serum Rho-associated protein kinase 1 (ROCK-1) were also evaluated along with histopathological examination of aorta specimens. Fasudil administration significantly decreased serum cholesterol, triglyceride (TG), and LDL and significantly increased serum HDL, with concomitant decrease in serum CK and LDH activities, NO, and restoration of serum TAC. Myocardial MDA significantly declined; SOD activity and GSH contents were restored. Serum ROCK-1 and VCAM-1 levels significantly declined as well. Vascular improvement was confirmed with histopathological examination, which revealed normal aortic intema with the absence of atheromas. Fasudil has promising anti-atherogenic activity mediated primarily via alleviation of hypercholesterolemia-induced oxidative stress and modulation of inflammatory response.

  15. Mechanical stimulation of cyclic tensile strain induces reduction of pluripotent related gene expressions via activation of Rho/ROCK and subsequent decreasing of AKT phosphorylation in human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Teramura, Takeshi; Takehara, Toshiyuki; Onodera, Yuta; Nakagawa, Koichi; Hamanishi, Chiaki; Fukuda, Kanji

    2012-01-01

    Highlights: ► Mechanical stimulation is an important factor for regulation of stem cell fate. ► Cyclic stretch to human induced pluripotent stem cells activated small GTPase Rho. ► Rho-kinase activation attenuated pluripotency via inhibition of AKT activation. ► This reaction could be reproduced only by transfection of dominant active Rho. ► Rho/ROCK are important molecules in mechanotransduction and control of stemness. -- Abstract: Mechanical stimulation has been shown to regulate the proliferation and differentiation of stem cells. However, the effects of the mechanical stress on the stemness or related molecular mechanisms have not been well determined. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are used as good materials for cell transplantation therapy and research of mammalian development, since they can self-renew infinitely and differentiate into various cell lineages. Here we demonstrated that the mechanical stimulation to human iPS cells altered alignment of actin fibers and expressions of the pluripotent related genes Nanog, POU5f1 and Sox2. In the mechanically stimulated iPS cells, small GTPase Rho was activated and interestingly, AKT phosphorylation was decreased. Inhibition of Rho-associated kinase ROCK recovered the AKT phosphorylation and the gene expressions. These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator.

  16. Toll-Like Receptor 9-Dependent AMPKα Activation Occurs via TAK1 and Contributes to RhoA/ROCK Signaling and Actin Polymerization in Vascular Smooth Muscle Cells.

    Science.gov (United States)

    McCarthy, Cameron G; Wenceslau, Camilla F; Ogbi, Safia; Szasz, Theodora; Webb, R Clinton

    2018-04-01

    Traditionally, Toll-like receptor 9 (TLR9) signals through an MyD88-dependent cascade that results in proinflammatory gene transcription. Recently, it was reported that TLR9 also participates in a stress tolerance signaling cascade in nonimmune cells. In this noncanonical pathway, TLR9 binds to and inhibits sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase 2 (SERCA2), modulating intracellular calcium handling, and subsequently resulting in the activation of 5'-AMP-activated protein kinase α (AMPK α ). We have previously reported that TLR9 causes increased contraction in isolated arteries; however, the mechanisms underlying this vascular dysfunction need to be further clarified. Therefore, we hypothesized that noncanonical TLR9 signaling was also present in vascular smooth muscle cells (VSMCs) and that it mediates enhanced contractile responses through SERCA2 inhibition. To test these hypotheses, aortic microsomes, aortic VSMCs, and isolated arteries from male Sprague-Dawley rats were incubated with vehicle or TLR9 agonist (ODN2395). Despite clear AMPK α activation after treatment with ODN2395, SERCA2 activity was unaffected. Alternatively, ODN2395 caused the phosphorylation of AMPK α via transforming growth factor β -activated kinase 1 (TAK1), a kinase involved in TLR9 inflammatory signaling. Downstream, we hypothesized that that TLR9 activation of AMPK α may be important in mediating actin cytoskeleton reorganization. ODN2395 significantly increased the filamentous-to-globular actin ratio, as well as indices of RhoA/Rho-associated protein kinase (ROCK) activation, with the latter being prevented by AMPK α inhibition. In conclusion, AMPK α phosphorylation after TLR9 activation in VSMCs appears to be an extension of traditional inflammatory signaling via TAK1, as opposed to SERCA2 inhibition and the noncanonical pathway. Nonetheless, TLR9-AMPK α signaling can mediate VSMC function via RhoA/ROCK activation and actin polymerization. Copyright © 2018 by The

  17. Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Kawamura, Miwako; Izumo, Shuji

    2011-01-01

    Methylmercury (MeHg) is an environmental neurotoxicant which induces neuropathological changes in both the central nervous and peripheral sensory nervous systems. Our recent study demonstrated that down-regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1), which is known to promote neuritic extension, preceded MeHg-induced damage in cultured cortical neurons, suggesting that MeHg-mediated axonal degeneration is due to the disturbance of neuritic extension. Therefore we hypothesized that MeHg-induced axonal degeneration might be caused by neuritic extension/retraction incoordination. This idea brought our attention to the Ras homolog gene (Rho)/Rho-associated coiled coil-forming protein kinase (ROCK) pathway because it has been known to be associated with the development of axon and apoptotic neuronal cell death. Here we show that inhibition of the Rho/ROCK pathway prevents MeHg-intoxication both in vitro and in vivo. A Rho inhibitor, C3 toxin, and 2 ROCK inhibitors, Fasudil and Y-27632, significantly protected against MeHg-induced axonal degeneration and apoptotic neuronal cell death in cultured cortical neuronal cells exposed to 100 nM MeHg for 3 days. Furthermore, Fasudil partially prevented the loss of large pale neurons in dorsal root ganglia, axonal degeneration in dorsal spinal root nerves, and vacuolar degeneration in the dorsal columns of the spinal cord in MeHg-intoxicated model rats (20 ppm MeHg in drinking water for 28 days). Hind limb crossing sign, a characteristic MeHg-intoxicated sign, was significantly suppressed in this model. The results suggest that inhibition of the Rho/ROCK pathway rescues MeHg-mediated neuritic extension/retraction incoordination and is effective for the prevention of MeHg-induced axonal degeneration and apoptotic neuronal cell death.

  18. Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

    Science.gov (United States)

    Singh, Jagmohan; Kumar, Sumit; Phillips, Benjamin

    2015-01-01

    The extracellular signal that triggers activation of rho-associated kinase (RhoA/ROCK), the major molecular determinant of basal internal anal sphincter (IAS) smooth muscle tone, is not known. Using human IAS tissues, we identified the presence of the biosynthetic machineries for angiotensin II (ANG II), thromboxane A2 (TXA2), and prostaglandin F2α (PGF2α). These end products of the renin-angiotensin system (RAS) (ANG II) and arachidonic acid (TXA2 and PGF2α) pathways and their effects in human IAS vs. rectal smooth muscle (RSM) were studied. A multipronged approach utilizing immunocytochemistry, Western blot analyses, and force measurements was implemented. Additionally, in a systematic analysis of the effects of respective inhibitors along different steps of biosynthesis and those of antagonists, their end products were evaluated either individually or in combination. To further describe the molecular mechanism for the IAS tone via these pathways, we monitored RhoA/ROCK activation and its signal transduction cascade. Data showed characteristically higher expression of biosynthetic machineries of RAS and AA pathways in the IAS compared with the RSM. Additionally, specific inhibition of the arachidonic acid (AA) pathway caused ∼80% decrease in the IAS tone, whereas that of RAS lead to ∼20% decrease. Signal transduction studies revealed that the end products of both AA and RAS pathways cause increase in the IAS tone via activation of RhoA/ROCK. Both AA and RAS (via the release of their end products TXA2, PGF2α, and ANG II, respectively), provide extracellular signals which activate RhoA/ROCK for the maintenance of the basal tone in human IAS. PMID:25882611

  19. Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway.

    Science.gov (United States)

    Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin

    2017-05-01

    Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

  20. Mechanical stimulation of cyclic tensile strain induces reduction of pluripotent related gene expressions via activation of Rho/ROCK and subsequent decreasing of AKT phosphorylation in human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Teramura, Takeshi, E-mail: teramura@med.kindai.ac.jp [Institute of Advanced Clinical Medicine, Kinki University, Faculty of Medicine, Osaka (Japan); Takehara, Toshiyuki; Onodera, Yuta [Institute of Advanced Clinical Medicine, Kinki University, Faculty of Medicine, Osaka (Japan); Nakagawa, Koichi; Hamanishi, Chiaki [Department of Orthopaedic Surgery, Kinki University, Faculty of Medicine, Osaka (Japan); Fukuda, Kanji [Institute of Advanced Clinical Medicine, Kinki University, Faculty of Medicine, Osaka (Japan); Department of Orthopaedic Surgery, Kinki University, Faculty of Medicine, Osaka (Japan)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Mechanical stimulation is an important factor for regulation of stem cell fate. Black-Right-Pointing-Pointer Cyclic stretch to human induced pluripotent stem cells activated small GTPase Rho. Black-Right-Pointing-Pointer Rho-kinase activation attenuated pluripotency via inhibition of AKT activation. Black-Right-Pointing-Pointer This reaction could be reproduced only by transfection of dominant active Rho. Black-Right-Pointing-Pointer Rho/ROCK are important molecules in mechanotransduction and control of stemness. -- Abstract: Mechanical stimulation has been shown to regulate the proliferation and differentiation of stem cells. However, the effects of the mechanical stress on the stemness or related molecular mechanisms have not been well determined. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are used as good materials for cell transplantation therapy and research of mammalian development, since they can self-renew infinitely and differentiate into various cell lineages. Here we demonstrated that the mechanical stimulation to human iPS cells altered alignment of actin fibers and expressions of the pluripotent related genes Nanog, POU5f1 and Sox2. In the mechanically stimulated iPS cells, small GTPase Rho was activated and interestingly, AKT phosphorylation was decreased. Inhibition of Rho-associated kinase ROCK recovered the AKT phosphorylation and the gene expressions. These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator.

  1. ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation.

    Science.gov (United States)

    Maldonado, Maricela; Luu, Rebeccah J; Ramos, Michael E P; Nam, Jin

    2016-09-01

    Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632. Copyright © 2016 Helmholtz Zentrum München. Published by Elsevier B.V. All rights reserved.

  2. ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation

    Directory of Open Access Journals (Sweden)

    Maricela Maldonado

    2016-09-01

    Full Text Available Robust control of human induced pluripotent stem cell (hIPSC differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36 h. Simultaneously, epithelial-to-mesenchymal (EMT transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632.

  3. [Effect of Different Stimulating Strength of Electroacupuncture on Gastrointestinal Motility and RhoA/ROCK Signaling in Gastric Antral Smooth Muscle in Diabetic Gastroparesis Rats].

    Science.gov (United States)

    Wu, Xue-Fen; Chen, Xiao-Li; Zheng, Xue-Na; Guo, Xin; Xie, Zhi-Qiang; Liu, Li; Wei, Xin-Ran; Yue, Zeng-Hui

    2018-03-25

    To observe the effect of different strength of electroacupuncture (EA) stimulation on gastrointestinal motility and Ras homolog gene family member (RhoA)/Rho associated coiled-coil forming protein kinase (ROCK) signaling in diabetic gastroparesis (DGP) rats, so as to reveal the underlying mechanisms of EA for improving DGP. Sixty SD rats were randomly and equally divided into blank control, DGP model, weak EA, medium EA, and strong EA groups ( n =12 rats in each). The DGP model was established by intraperitoneal injection of streptozotocin (STZ, 55 mmol/kg, 2%) and high-sugar and high-fat fodder feeding for 8 weeks. EA (0.12, 0.24, 0.36 mA, 20 Hz/100 Hz) was applied to "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Liangmen" (ST 21) for 20 min, once daily for 15 successive days. Blood glucose levels were measured weekly with blood glucose meter and blood glucose test paper. Fecal phenol red excretion method was used to display gastric emptying and small intestinal propulsion function. The expression of RhoA protein in the gastric antral smooth muscle tissue was detected by immunohistochemistry and Western blot (WB), separately, and that of ROCK, myosin phosphatase target subunit 1 (MYPT 1) and phosphorylated (p)-MYPT 1 proteins in gastric antrum detected by WB. Compared with the blank control group, the gastric emptying rate and small intestine propulsion rate of the model group were significantly decreased ( P ROCK, MYPT 1 and p-MYPT 1 proteins in the gastric antrum were significantly down-regulated relevant to the control group ( P ROCK, MYPT 1 and p-MYPT 1 proteins were significantly increased in the strong, medium and weak EA stimulation groups ( P ROCK, MYPT 1 and p-MYPT 1 proteins, and obviously superior to the medium stimulation in up-regulating RhoA and MYPT 1 protein levels ( P ROCK, MYPT 1 and p-MYPT 1 proteins ( P ROCK and p-MYPT 1 proteins ( P >0.05). Electroacupuncture stimulation of ST 36-SP 6-ST 21 at 0.12, 0.24 and 0.36 mA can promote the

  4. Ginsenoside Rg1 protects rat bone marrow mesenchymal stem cells against ischemia induced apoptosis through miR-494-3p and ROCK-1.

    Science.gov (United States)

    Zheng, Hui-Zhen; Fu, Xue-Kun; Shang, Jiu-Long; Lu, Rong-Xi; Ou, Yong-Fang; Chen, Chun-Ling

    2018-03-05

    This study aimed to verify the cytoprotective effect of ginsenoside Rg1 in vivo, and to elucidate the mechanism of Rg1 in the ischemic microenvironment. Male rat bone marrow mesenchymal stem cells (rBMSCs) or rBMSCs treated with Rg1 were injected into ischemic region of the arterial embolism hind limb in female rats. Behavioral and histological data, obtained one-week post injection, showed that rBMSCs with Rg1 could improve the survival rate of BMSCs and enhance the therapeutic effects. rBMSCs treated with hypoxia and serum deprivation for 24h (H/SD-rBMSCs) showed the up-regulated expression of ras homolog family member A (RhoA), Rho associated coiled-coil containing protein kinase 1 (ROCK-1), myosin light chain 2 (MLC-2), Bcl2 associated agonist of cell death (Bad) and Bcl2 associated X, apoptosis regulator (Bax); while the expression of miR-148b-3p, miR-148b-5p and miR-494-3p was down-regulated. H/SD with Rg1 treatment (H/SD+Rg1-rBMSCs) inhibited the expression of ROCK-1, MLC-2, Bad and Bax, increased the expression of Bcl-2, miR-494-3p. After ROCK-1 knockout, the expression of Bad and Bax were downregulated and Bcl-2 upregulated, but Rg1 no longer altered their expression. Mir-494-3p functional study established that miR-494-3 mimic downregulated and miR-494-3 inhibitor upregulated ROCK-1 gene expression, Rg1 did not have the ability to change the ROCK gene expression after loss of function of miR-494-3p. Also, the function loss of mir-494-3p promoted apoptosis; otherwise reduced apoptosis. The anti-apoptotic effect of Rg1 disappeared after mir-494-3p loss or gain function. In conclusion, Ginsenoside Rg1 has shown to have protective effects on ischemic-induced rBMSCs apoptosis through mir-494-3p→ROCK-1→Bcl-2 signaling pathway. Copyright © 2018. Published by Elsevier B.V.

  5. ROCK inhibitors in ocular disease

    Directory of Open Access Journals (Sweden)

    Eva Halasz

    2016-12-01

    Full Text Available Rho kinases (ROCKs have a crucial role in actin-cytoskeletal reorganization and thus are involved in broad aspects of cell motility, from smooth muscle contraction to neurite outgrowth. The first marketed ROCK inhibitor, called fasudil, has been used safely for treatment of cerebral vasospasm since 1995 in Japan. During the succeeding decades ROCK inhibitors have been applied in many pathological conditions from central nervous system disorders to cardiovascular disease as potential therapeutic agents or experimental tools to help understand the underlying (pathomechanisms. In 2014, a fasudil derivate named ripasudil was accepted for clinical use in glaucoma and ocular hypertension. Since ROCK kinases are widely expressed in ocular tissues, they have been implicated in the pathology of many ocular conditions such as corneal dysfunction, glaucoma, cataract, diabetic retinopathy, age-related macular degeneration, and retinal detachment. This paper aims to provide an overview of the most recent status/application of ROCK inhibitors in the field of eye disease.

  6. Rock fragmentation

    Energy Technology Data Exchange (ETDEWEB)

    Brown, W.S.; Green, S.J.; Hakala, W.W.; Hustrulid, W.A.; Maurer, W.C. (eds.)

    1976-01-01

    Experts in rock mechanics, mining, excavation, drilling, tunneling and use of underground space met to discuss the relative merits of a wide variety of rock fragmentation schemes. Information is presented on novel rock fracturing techniques; tunneling using electron beams, thermocorer, electric spark drills, water jets, and diamond drills; and rock fracturing research needs for mining and underground construction. (LCL)

  7. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase.

    Directory of Open Access Journals (Sweden)

    Mutsuki Amano

    Full Text Available BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity.

  8. Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor recovery after spinal cord injury: a systematic review and meta-analysis.

    Science.gov (United States)

    Watzlawick, Ralf; Sena, Emily S; Dirnagl, Ulrich; Brommer, Benedikt; Kopp, Marcel A; Macleod, Malcolm R; Howells, David W; Schwab, Jan M

    2014-01-01

    Blockade of small GTPase-RhoA signaling pathway is considered a candidate translational strategy to improve functional outcome after spinal cord injury (SCI) in humans. Pooling preclinical evidence by orthodox meta-analysis is confounded by missing data (publication bias). To conduct a systematic review and meta-analysis of RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) blocking approaches to (1) analyze the impact of bias that may lead to inflated effect sizes and (2) determine the normalized effect size of functional locomotor recovery after experimental thoracic SCI. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the effect of RhoA/ROCK inhibitors (C3-exoenzmye, fasudil, Y-27632, ibuprofen, siRhoA, and p21) in experimental spinal cord hemisection, contusion, or transection on locomotor recovery measured by the Basso, Beattie, and Bresnahan score or the Basso Mouse Scale for Locomotion. Two investigators independently assessed the identified studies. Details of individual study characteristics from each publication were extracted and effect sizes pooled using a random effects model. We assessed risk for bias using a 9-point-item quality checklist and calculated publication bias with Egger regression and the trim and fill method. A stratified meta-analysis was used to assess the impact of study characteristics on locomotor recovery. Thirty studies (725 animals) were identified. RhoA/ROCK inhibition was found to improve locomotor outcome by 21% (95% CI, 16.0-26.6). Assessment of publication bias by the trim and fill method suggested that 30% of experiments remain unpublished. Inclusion of these theoretical missing studies suggested a 27% overestimation of efficacy, reducing the overall efficacy to a 15% improvement in locomotor recovery. Low study quality was associated with larger estimates of neurobehavioral outcome. Taking into account

  9. Rock Art

    Science.gov (United States)

    Henn, Cynthia A.

    2004-01-01

    There are many interpretations for the symbols that are seen in rock art, but no decoding key has ever been discovered. This article describes one classroom's experiences with a lesson on rock art--making their rock art and developing their own personal symbols. This lesson allowed for creativity, while giving an opportunity for integration…

  10. ROCK1 and ROCK2 are Required for Non-Small Cell Lung Cancer Anchorage-Independent Growth and Invasion

    OpenAIRE

    Vigil, Dominico; Kim, Tai Young; Plachco, Ana; Garton, Andrew J.; Castaldo, Linda; Pachter, Jonathan A.; Dong, Hanqing; Chen, Xin; Tokar, Brianna; Campbell, Sharon L.; Der, Channing J.

    2012-01-01

    Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor anti-tumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, ...

  11. 'Escher' Rock

    Science.gov (United States)

    2004-01-01

    [figure removed for brevity, see original site] Chemical Changes in 'Endurance' Rocks [figure removed for brevity, see original site] Figure 1 This false-color image taken by NASA's Mars Exploration Rover Opportunity shows a rock dubbed 'Escher' on the southwestern slopes of 'Endurance Crater.' Scientists believe the rock's fractures, which divide the surface into polygons, may have been formed by one of several processes. They may have been caused by the impact that created Endurance Crater, or they might have arisen when water leftover from the rock's formation dried up. A third possibility is that much later, after the rock was formed, and after the crater was created, the rock became wet once again, then dried up and developed cracks. Opportunity has spent the last 14 sols investigating Escher, specifically the target dubbed 'Kirchner,' and other similar rocks with its scientific instruments. This image was taken on sol 208 (Aug. 24, 2004) by the rover's panoramic camera, using the 750-, 530- and 430-nanometer filters. The graph above shows that rocks located deeper into 'Endurance Crater' are chemically altered to a greater degree than rocks located higher up. This chemical alteration is believed to result from exposure to water. Specifically, the graph compares ratios of chemicals between the deep rock dubbed 'Escher,' and the more shallow rock called 'Virginia,' before (red and blue lines) and after (green line) the Mars Exploration Rover Opportunity drilled into the rocks. As the red and blue lines indicate, Escher's levels of chlorine relative to Virginia's went up, and sulfur down, before the rover dug a hole into the rocks. This implies that the surface of Escher has been chemically altered to a greater extent than the surface of Virginia. Scientists are still investigating the role water played in influencing this trend. These data were taken by the rover's alpha particle X-ray spectrometer.

  12. Recreating Rocks

    DEFF Research Database (Denmark)

    Posth, Nicole R

    2008-01-01

    Nicole Posth and colleagues spent a month touring South African rock formations in their quest to understand the origin of ancient iron and silicate layers.......Nicole Posth and colleagues spent a month touring South African rock formations in their quest to understand the origin of ancient iron and silicate layers....

  13. Art Rocks with Rock Art!

    Science.gov (United States)

    Bickett, Marianne

    2011-01-01

    This article discusses rock art which was the very first "art." Rock art, such as the images created on the stone surfaces of the caves of Lascaux and Altimira, is the true origin of the canvas, paintbrush, and painting media. For there, within caverns deep in the earth, the first artists mixed animal fat, urine, and saliva with powdered minerals…

  14. RhoA/Rho-Kinase in the Cardiovascular System.

    Science.gov (United States)

    Shimokawa, Hiroaki; Sunamura, Shinichiro; Satoh, Kimio

    2016-01-22

    Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho-kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase-dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system. © 2016 American Heart Association, Inc.

  15. Rock Physics

    DEFF Research Database (Denmark)

    Fabricius, Ida Lykke

    2017-01-01

    Rock physics is the discipline linking petrophysical properties as derived from borehole data to surface based geophysical exploration data. It can involve interpretation of both elastic wave propagation and electrical conductivity, but in this chapter focus is on elasticity. Rock physics is based...... on continuum mechanics, and the theory of elasticity developed for statics becomes the key to petrophysical interpretation of velocity of elastic waves. In practice, rock physics involves interpretation of well logs including vertical seismic profiling (VSP) and analysis of core samples. The results...

  16. Dissecting the roles of ROCK isoforms in stress-induced cell detachment

    OpenAIRE

    Shi, Jianjian; Surma, Michelle; Zhang, Lumin; Wei, Lei

    2013-01-01

    The homologous Rho kinases, ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant. Using mouse embryonic fibroblasts (MEFs) derived from ROCK1 ?/? and ROCK2?/? mice, we have recently reported that they play different roles in regulating doxorubicin-induced stress fiber disassembly and cell detachment: ROCK1 is involved in destabilizing the actin cytoskeleton and cell detachment, whereas ROCK2 is required for stabilizing the actin...

  17. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G

    1993-01-01

    The present review on casein kinases focuses mainly on the possible metabolic role of CK-2, with special emphasis on its behavior in pathological tissues. From these data at least three ways to regulate CK-2 activity emerge: (i) CK-2 activity changes during embryogenesis, being high at certain...

  18. Rocking pneumonia

    OpenAIRE

    Rijkers, Ger T.; Rodriguez Gomez, Maria

    2017-01-01

    Ever since Chuck Berry coined the term “rocking pneumonia” in his 1956 song “Roll over Beethoven”, pneumonia has been mentioned frequently in modern blues and rock songs. We analyzed the lyrics of these songs to examine how various elements of pneumonia have been represented in popular music, specifically the cause of pneumonia, the risk groups, comorbidity (such as the boogie woogie flu), the clinical symptoms, and treatment and outcome. Up to this day, songwriters suggest that pneumonia is ...

  19. Kinases and Cancer

    OpenAIRE

    Jonas Cicenas; Egle Zalyte; Amos Bairoch; Pascale Gaudet

    2018-01-01

    Protein kinases are a large family of enzymes catalyzing protein phosphorylation. The human genome contains 518 protein kinase genes, 478 of which belong to the classical protein kinase family and 40 are atypical protein kinases [...

  20. The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers.

    Directory of Open Access Journals (Sweden)

    Nil Emre

    Full Text Available BACKGROUND: Due to the inherent sensitivity of human embryonic stem cells (hESCs to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. CONCLUSIONS/SIGNIFICANCE: The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types

  1. Source rock

    Directory of Open Access Journals (Sweden)

    Abubakr F. Makky

    2014-03-01

    Full Text Available West Beni Suef Concession is located at the western part of Beni Suef Basin which is a relatively under-explored basin and lies about 150 km south of Cairo. The major goal of this study is to evaluate the source rock by using different techniques as Rock-Eval pyrolysis, Vitrinite reflectance (%Ro, and well log data of some Cretaceous sequences including Abu Roash (E, F and G members, Kharita and Betty formations. The BasinMod 1D program is used in this study to construct the burial history and calculate the levels of thermal maturity of the Fayoum-1X well based on calibration of measured %Ro and Tmax against calculated %Ro model. The calculated Total Organic Carbon (TOC content from well log data compared with the measured TOC from the Rock-Eval pyrolysis in Fayoum-1X well is shown to match against the shale source rock but gives high values against the limestone source rock. For that, a new model is derived from well log data to calculate accurately the TOC content against the limestone source rock in the study area. The organic matter existing in Abu Roash (F member is fair to excellent and capable of generating a significant amount of hydrocarbons (oil prone produced from (mixed type I/II kerogen. The generation potential of kerogen in Abu Roash (E and G members and Betty formations is ranging from poor to fair, and generating hydrocarbons of oil and gas prone (mixed type II/III kerogen. Eventually, kerogen (type III of Kharita Formation has poor to very good generation potential and mainly produces gas. Thermal maturation of the measured %Ro, calculated %Ro model, Tmax and Production index (PI indicates that Abu Roash (F member exciting in the onset of oil generation, whereas Abu Roash (E and G members, Kharita and Betty formations entered the peak of oil generation.

  2. Intellektuaalne rock

    Index Scriptorium Estoniae

    2007-01-01

    Briti laulja-helilooja ja näitleja Toyah Willcox ning Bill Rieflin ansamblist R.E.M. ja Pat Mastelotto King Krimsonist esinevad koos ansamblitega The Humans ja Tuner 25. okt. Tallinnas Rock Cafés ja 27. okt Tartu Jaani kirikus

  3. Igneous Rocks

    Science.gov (United States)

    Doe, Bruce R.

    “Igneous Rocks was written for undergraduate geology majors who have had a year of college-level chemistry and a course in mineralogy … and for beginning graduate students. Geologists working in industry, government, or academia should find this text useful as a guide to the technical literature up to 1981 and as an overview of topics with which they have not worked but which may have unanticipated pertinence to their own projects.” So starts the preface to this textbook.As one who works part time in research on igneous rocks, especially as they relate to mineral deposits, I have been looking for such a book with this avowed purpose in a field that has a choking richness of evolving terminology and a bewildering volume of interdisciplinary literature. In addition to the standard topics of igneous petrology, the book contains a chapter on the role of igneous activity in the genesis of mineral deposits, its value to geothermal energy, and the potential of igneous rocks as an environment for nuclear waste disposal. These topics are presented rather apologetically in the preface, but the author is to be applauded for including this chapter. The apology shows just how new these interests are to petrology. Recognition is finally coming that, for example, mineral deposits are not “sports of nature,” a view held even by many economic geologists as recently as the early 1960's; instead they are perfectly ordinary geochemical features formed by perfectly ordinary geologic processes. In fact, the mineral deposits and their attendant alteration zones probably have as much to tell us about igneous rocks as the igneous rocks have to tell us about mineral deposits.

  4. The Rho kinases I and II regulate different aspects of myosin II activity

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Multhaupt, Hinke A B; Couchman, John R

    2005-01-01

    The homologous mammalian rho kinases (ROCK I and II) are assumed to be functionally redundant, based largely on kinase construct overexpression. As downstream effectors of Rho GTPases, their major substrates are myosin light chain and myosin phosphatase. Both kinases are implicated in microfilament...... bundle assembly and smooth muscle contractility. Here, analysis of fibroblast adhesion to fibronectin revealed that although ROCK II was more abundant, its activity was always lower than ROCK I. Specific reduction of ROCK I by siRNA resulted in loss of stress fibers and focal adhesions, despite...

  5. White Rock

    Science.gov (United States)

    2002-01-01

    (Released 19 April 2002) The Science 'White Rock' is the unofficial name for this unusual landform which was first observed during the Mariner 9 mission in the early 1970's. As later analysis of additional data sets would show, White Rock is neither white nor dense rock. Its apparent brightness arises from the fact that the material surrounding it is so dark. Images from the Mars Global Surveyor MOC camera revealed dark sand dunes surrounding White Rock and on the floor of the troughs within it. Some of these dunes are just apparent in the THEMIS image. Although there was speculation that the material composing White Rock could be salts from an ancient dry lakebed, spectral data from the MGS TES instrument did not support this claim. Instead, the White Rock deposit may be the erosional remnant of a previously more continuous occurrence of air fall sediments, either volcanic ash or windblown dust. The THEMIS image offers new evidence for the idea that the original deposit covered a larger area. Approximately 10 kilometers to the southeast of the main deposit are some tiny knobs of similarly bright material preserved on the floor of a small crater. Given that the eolian erosion of the main White Rock deposit has produced isolated knobs at its edges, it is reasonable to suspect that the more distant outliers are the remnants of a once continuous deposit that stretched at least to this location. The fact that so little remains of the larger deposit suggests that the material is very easily eroded and simply blows away. The Story Fingers of hard, white rock seem to jut out like icy daggers across a moody Martian surface, but appearances can be deceiving. These bright, jagged features are neither white, nor icy, nor even hard and rocky! So what are they, and why are they so different from the surrounding terrain? Scientists know that you can't always trust what your eyes see alone. You have to use other kinds of science instruments to measure things that our eyes can

  6. Rock stresses (Grimsel rock laboratory)

    International Nuclear Information System (INIS)

    Pahl, A.; Heusermann, S.; Braeuer, V.; Gloeggler, W.

    1989-01-01

    On the research and development project 'Rock Stress Measurements' the BGR has developed and tested several test devices and methods at GTS for use in boreholes at a depth of 200 m and has carried out rock mechanical and engineering geological investigations for the evaluation and interpretation of the stress measurements. The first time a computer for data processing was installed in the borehole together with the BGR-probe. Laboratory tests on hollow cylinders were made to study the stress-deformation behavior. To validate and to interprete the measurement results some test methods were modelled using the finite-element method. The dilatometer-tests yielded high values of Young's modulus, whereas laboratory tests showed lower values with a distinct deformation anisotropy. Stress measurements with the BGR-probe yielded horizontal stresses being higher than the theoretical overburden pressure and vertical stresses which agree well with the theoretical overburden pressure. These results are comparable to the results of the hydraulic fracturing tests, whereas stresses obtained with CSIR-triaxial cells are generally lower. The detailed geological mapping of the borehole indicated relationships between stress and geology. With regard to borehole depth different zones of rock structure joint frequency, joint orientation, and orientation of microfissures as well as stress magnitude, stress direction, and degree of deformation anisotropy could be distinguished. (orig./HP) [de

  7. Thermal Inertia of Rocks and Rock Populations

    Science.gov (United States)

    Golombek, M. P.; Jakosky, B. M.; Mellon, M. T.

    2001-01-01

    The effective thermal inertia of rock populations on Mars and Earth is derived from a model of effective inertia versus rock diameter. Results allow a parameterization of the effective rock inertia versus rock abundance and bulk and fine component inertia. Additional information is contained in the original extended abstract.

  8. Myotonic dystrophy protein kinase (DMPK) induces actin cytoskeletal reorganization and apoptotic-like blebbing in lens cells

    Science.gov (United States)

    Jin, S.; Shimizu, M.; Balasubramanyam, A.; Epstein, H. F.

    2000-01-01

    DMPK, the product of the DM locus, is a member of the same family of serine-threonine protein kinases as the Rho-associated enzymes. In DM, membrane inclusions accumulate in lens fiber cells producing cataracts. Overexpression of DMPK in cultured lens epithelial cells led to apoptotic-like blebbing of the plasma membrane and reorganization of the actin cytoskeleton. Enzymatically active DMPK was necessary for both effects; inactive mutant DMPK protein did not produce either effect. Active RhoA but not constitutive GDP-state mutant protein produced similar effects as DMPK. The similar actions of DMPK and RhoA suggest that they may function in the same regulatory network. The observed effects of DMPK may be relevant to the removal of membrane organelles during normal lens differentiation and the retention of intracellular membranes in DM lenses. Copyright 2000 Wiley-Liss, Inc.

  9. Water - rock interaction in different rock environments

    International Nuclear Information System (INIS)

    Lamminen, S.

    1995-01-01

    The study assesses the groundwater geochemistry and geological environment of 44 study sites for radioactive waste disposal. Initially, the study sites were divided by rock type into 5 groups: (1) acid - intermediate rocks, (2) mafic - ultramafic rocks, (3) gabbros, amphibolites and gneisses that contain calc-silicate (skarn) rocks, (4) carbonates and (5) sandstones. Separate assessments are made of acid - intermediate plutonic rocks and of a subgroup that comprises migmatites, granite and mica gneiss. These all belong to the group of acid - intermediate rocks. Within the mafic -ultramafic rock group, a subgroup that comprises mafic - ultramafic plutonic rocks, serpentinites, mafic - ultramafic volcanic rocks and volcanic - sedimentary schists is also evaluated separately. Bedrock groundwaters are classified by their concentration of total dissolved solids as fresh, brackish, saline, strongly saline and brine-class groundwaters. (75 refs., 24 figs., 3 tabs.)

  10. CERN Rocks

    CERN Multimedia

    2004-01-01

    The 15th CERN Hardronic Festival took place on 17 July on the terrace of Rest 3 (Prévessin). Over 1000 people, from CERN and other International Organizations, came to enjoy the warm summer night, and to watch the best of the World's High Energy music. Jazz, rock, pop, country, metal, blues, funk and punk blasted out from 9 bands from the CERN Musiclub and Jazz club, alternating on two stages in a non-stop show.  The night reached its hottest point when The Canettes Blues Band got everybody dancing to sixties R&B tunes (pictured). Meanwhile, the bars and food vans were working at full capacity, under the expert management of the CERN Softball club, who were at the same time running a Softball tournament in the adjacent "Higgs Field". The Hardronic Festival is the main yearly CERN music event, and it is organized with the support of the Staff Association and the CERN Administration.

  11. Thymidine kinases in archaea

    DEFF Research Database (Denmark)

    Clausen, A.R.; Matakos, A.; Sandrini, Michael

    2006-01-01

    Twenty-six fully sequenced archaeal genomes were searched for genes coding for putative deoxyribonucleoside kinases (dNKs). We identified only 5 human-like thymidine kinase 1 genes (TK1s) and none for non-TK1 kinases. Four TK1s were identified in the Euryarchaea and one was found in the Crenarcha...

  12. Rollerjaw Rock Crusher

    Science.gov (United States)

    Peters, Gregory; Brown, Kyle; Fuerstenau, Stephen

    2009-01-01

    The rollerjaw rock crusher melds the concepts of jaw crushing and roll crushing long employed in the mining and rock-crushing industries. Rollerjaw rock crushers have been proposed for inclusion in geological exploration missions on Mars, where they would be used to pulverize rock samples into powders in the tens of micrometer particle size range required for analysis by scientific instruments.

  13. Diacylglycerol kinase ζ regulates RhoA activation via a kinase-independent scaffolding mechanism

    DEFF Research Database (Denmark)

    Ard, Ryan; Mulatz, Kirk; Abramovici, Hanan

    2012-01-01

    , but the underlying mechanisms are unclear. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, selectively dissociates Rac1 by stimulating PAK1-mediated phosphorylation of RhoGDI on Ser-101/174. Similarly, phosphorylation of RhoGDI on Ser-34 by protein kinase Cα (PKCα......GDI and was required for efficient interaction of PKCα and RhoA. DGKζ-null fibroblasts had condensed F-actin bundles and altered focal adhesion distribution, indicative of aberrant RhoA signaling. Two targets of the RhoA effector ROCK showed reduced phosphorylation in DGKζ-null cells. Collectively our findings suggest...

  14. Novel ROCK inhibitors for the treatment of pulmonary arterial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, Duncan; Hollingworth, Greg; Soldermann, Nicolas; Sprague, Elizabeth; Schuler, Walter; Vangrevelinghe, Eric; Duggan, Nicholas; Thomas, Matthew; Kosaka, Takatoshi; Waters, Nigel; van Eis, Maurice J. (Novartis)

    2014-10-01

    A novel class of selective inhibitors of ROCK1 and ROCK2 has been identified by structural based drug design. PK/PD experiments using a set of highly selective Rho kinase inhibitors suggest that systemic Rho kinase inhibition is linked to a reversible reduction in lymphocyte counts. These results led to the consideration of topical delivery of these molecules, and to the identification of a lead molecule 7 which shows promising PK and PD in a murine model of pulmonary hypertension after intra-tracheal dosing.

  15. Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors.

    Science.gov (United States)

    Amen, Yhiya; Zhu, Qinchang; Tran, Hai-Bang; Afifi, Mohamed S; Halim, Ahmed F; Ashour, Ahmed; Shimizu, Kuniyoshi

    2017-04-01

    Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes. The structure-activity relationship analysis was investigated. Our results suggest that the traditional uses of G. lingzhi might be in part due to the ROCK-I and ROCK-II inhibitory potential of this mushroom. Structure-activity relationship studies revealed some interesting features of the lanostane triterpenes that potentiate their Rho-kinase inhibition. These findings would be helpful for further studies on the design of Rho-kinase inhibitors from natural sources and open the door for contributions from other researchers for optimizing the development of natural Rho-kinase inhibitors.

  16. Rocks Can Wow? Yes, Rocks Can Wow!

    Science.gov (United States)

    Hardman, Sally; Luke, Sue

    2016-01-01

    Rocks and fossils appear in the National Curriculum of England science programmes of study for children in year 3 (ages 7-8). A frequently asked question is "How do you make the classification of rocks engaging?" In response to this request from a school, a set of interactive activities was designed and organised by tutors and students…

  17. Rock slope design guide.

    Science.gov (United States)

    2011-04-01

    This Manual is intended to provide guidance for the design of rock cut slopes, rockfall catchment, and : rockfall controls. Recommendations presented in this manual are based on research presented in Shakoor : and Admassu (2010) entitled Rock Slop...

  18. Rock Slope Design Criteria

    Science.gov (United States)

    2010-06-01

    Based on the stratigraphy and the type of slope stability problems, the flat lying, Paleozoic age, sedimentary : rocks of Ohio were divided into three design units: 1) competent rock design unit consisting of sandstones, limestones, : and siltstones ...

  19. The Rock Cycle

    Science.gov (United States)

    Singh, Raman J.; Bushee, Jonathan

    1977-01-01

    Presents a rock cycle diagram suitable for use at the secondary or introductory college levels which separates rocks formed on and below the surface, includes organic materials, and separates products from processes. (SL)

  20. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  1. Rock History and Culture

    OpenAIRE

    Gonzalez, Éric

    2013-01-01

    Two ambitious works written by French-speaking scholars tackle rock music as a research object, from different but complementary perspectives. Both are a definite must-read for anyone interested in the contextualisation of rock music in western popular culture. In Une histoire musicale du rock (i.e. A Musical History of Rock), rock music is approached from the point of view of the people – musicians and industry – behind the music. Christophe Pirenne endeavours to examine that field from a m...

  2. Identification and Structure-Function Analysis of Subfamily Selective G Protein-Coupled Receptor Kinase Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Homan, Kristoff T.; Larimore, Kelly M.; Elkins, Jonathan M.; Szklarz, Marta; Knapp, Stefan; Tesmer, John J.G. [Michigan; (Oxford)

    2015-02-13

    Selective inhibitors of individual subfamilies of G protein-coupled receptor kinases (GRKs) would serve as useful chemical probes as well as leads for therapeutic applications ranging from heart failure to Parkinson’s disease. To identify such inhibitors, differential scanning fluorimetry was used to screen a collection of known protein kinase inhibitors that could increase the melting points of the two most ubiquitously expressed GRKs: GRK2 and GRK5. Enzymatic assays on 14 of the most stabilizing hits revealed that three exhibit nanomolar potency of inhibition for individual GRKs, some of which exhibiting orders of magnitude selectivity. Most of the identified compounds can be clustered into two chemical classes: indazole/dihydropyrimidine-containing compounds that are selective for GRK2 and pyrrolopyrimidine-containing compounds that potently inhibit GRK1 and GRK5 but with more modest selectivity. The two most potent inhibitors representing each class, GSK180736A and GSK2163632A, were cocrystallized with GRK2 and GRK1, and their atomic structures were determined to 2.6 and 1.85 Å spacings, respectively. GSK180736A, developed as a Rho-associated, coiled-coil-containing protein kinase inhibitor, binds to GRK2 in a manner analogous to that of paroxetine, whereas GSK2163632A, developed as an insulin-like growth factor 1 receptor inhibitor, occupies a novel region of the GRK active site cleft that could likely be exploited to achieve more selectivity. However, neither compound inhibits GRKs more potently than their initial targets. This data provides the foundation for future efforts to rationally design even more potent and selective GRK inhibitors.

  3. ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity.

    Science.gov (United States)

    Daley, William P; Gervais, Elise M; Centanni, Samuel W; Gulfo, Kathryn M; Nelson, Deirdre A; Larsen, Melinda

    2012-01-01

    The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin β1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.

  4. Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation.

    Science.gov (United States)

    Avanzi, Mauro P; Goldberg, Francine; Davila, Jennifer; Langhi, Dante; Chiattone, Carlos; Mitchell, William Beau

    2014-03-01

    The processes of megakaryocyte polyploidization and demarcation membrane system (DMS) formation are crucial for platelet production, but the mechanisms controlling these processes are not fully determined. Inhibition of Rho kinase (ROCK) signalling leads to increased polyploidization in umbilical cord blood-derived megakaryocytes. To extend these findings we determined the effect of ROCK inhibition on development of the DMS and on proplatelet formation. The underlying mechanisms were explored by analysing the effect of ROCK inhibition on the expression of MYC and NFE2, which encode two transcription factors critical for megakaryocyte development. ROCK inhibition promoted DMS formation, and increased proplatelet formation and platelet release. Rho kinase inhibition also downregulated MYC and NFE2 expression in mature megakaryocytes, and this down-regulation correlated with increased proplatelet formation. Our findings suggest a model whereby ROCK inhibition drives polyploidization, DMS growth and proplatelet formation late in megakaryocyte maturation through downregulation of MYC and NFE2 expression. © 2014 John Wiley & Sons Ltd.

  5. Pyruvate kinase blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003357.htm Pyruvate kinase blood test To use the sharing features on this page, ... energy when oxygen levels are low. How the Test is Performed A blood sample is needed. In the laboratory, white blood ...

  6. ROCK inhibitor is not required for embryoid body formation from singularized human embryonic stem cells.

    Science.gov (United States)

    Pettinato, Giuseppe; Vanden Berg-Foels, Wendy S; Zhang, Ning; Wen, Xuejun

    2014-01-01

    We report a technology to form human embryoid bodies (hEBs) from singularized human embryonic stem cells (hESCs) without the use of the p160 rho-associated coiled-coil kinase inhibitor (ROCKi) or centrifugation (spin). hEB formation was tested under four conditions: +ROCKi/+spin, +ROCKi/-spin, -ROCKi/+spin, and -ROCKi/-spin. Cell suspensions of BG01V/hOG and H9 hESC lines were pipetted into non-adherent hydrogel substrates containing defined microwell arrays. hEBs of consistent size and spherical geometry can be formed in each of the four conditions, including the -ROCKi/-spin condition. The hEBs formed under the -ROCKi/-spin condition differentiated to develop the three embryonic germ layers and tissues derived from each of the germ layers. This simplified hEB production technique offers homogeneity in hEB size and shape to support synchronous differentiation, elimination of the ROCKi xeno-factor and rate-limiting centrifugation treatment, and low-cost scalability, which will directly support automated, large-scale production of hEBs and hESC-derived cells needed for clinical, research, or therapeutic applications.

  7. Rock Cycle Roulette.

    Science.gov (United States)

    Schmidt, Stan M.; Palmer, Courtney

    2000-01-01

    Introduces an activity on the rock cycle. Sets 11 stages representing the transitions of an earth material in the rock cycle. Builds six-sided die for each station, and students move to the stations depending on the rolling side of the die. Evaluates students by discussing several questions in the classroom. Provides instructional information for…

  8. Rock engineering in Finland

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    Contains a large collection of short articles concerned with tunnels and underground caverns and their construction and use. The articles are grouped under the following headings: use of the subsurface space; water supply; waste water services; energy management (includes articles on power stations, district heating and oil storage and an article on coal storage); multipurpose tunnels; waste disposal; transport; shelters; sporting and recreational amenities located in rock caverns; storage facilities; industrial, laboratory, and service facilities; rock foundations; tourism and culture; utilization of rock masses; research on the disposal of nuclear waste; training and research in the field of rock engineering; site investigation techniques; design of structures in rock; construction; the environment and occupational safety; modern equipment technology; underground space in Helsinki.

  9. Phosphorylation of the Yeast Choline Kinase by Protein Kinase C

    Science.gov (United States)

    Choi, Mal-Gi; Kurnov, Vladlen; Kersting, Michael C.; Sreenivas, Avula; Carman, George M.

    2005-01-01

    The Saccharomyces cerevisiae CKI1-encoded choline kinase catalyzes the committed step in phosphatidylcholine synthesis via the Kennedy pathway. The enzyme is phosphorylated on multiple serine residues, and some of this phosphorylation is mediated by protein kinase A. In this work, we examined the hypothesis that choline kinase is also phosphorylated by protein kinase C. Using choline kinase as a substrate, protein kinase C activity was dose- and time-dependent, and dependent on the concentrations of choline kinase (Km = 27 μg/ml) and ATP (Km = 15 μM). This phosphorylation, which occurred on a serine residue, was accompanied by a 1.6-fold stimulation of choline kinase activity. The synthetic peptide SRSSS25QRRHS (Vmax/Km = 17.5 mM-1 μmol min-1 mg-1) that contains the protein kinase C motif for Ser25 was a substrate for protein kinase C. A Ser25 to Ala (S25A) mutation in choline kinase resulted in a 60% decrease in protein kinase C phosphorylation of the enzyme. Phosphopeptide mapping analysis of the S25A mutant enzyme confirmed that Ser25 was a protein kinase C target site. In vivo, the S25A mutation correlated with a decrease (55%) in phosphatidylcholine synthesis via the Kennedy pathway whereas an S25D phosphorylation site mimic correlated with an increase (44%) in phosphatidylcholine synthesis. Whereas the S25A (protein kinase C site) mutation did not affect the phosphorylation of choline kinase by protein kinase A, the S30A (protein kinase A site) mutation caused a 46% reduction in enzyme phosphorylation by protein kinase C. A choline kinase synthetic peptide (SQRRHS30LTRQ) containing Ser30 was a substrate (Vmax/Km = 3.0 mM−1 μmol min−1 mg−1) for protein kinase C. Comparison of phosphopeptide maps of the wild type and S30A mutant choline kinase enzymes phosphorylated by protein kinase C confirmed that Ser30 was also a target site for protein kinase C. PMID:15919656

  10. Enterococcus faecalis phosphomevalonate kinase

    Science.gov (United States)

    Doun, Stephanie S.; Burgner, John W.; Briggs, Scott D.; Rodwell, Victor W.

    2005-01-01

    The six enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis represent potential for addressing a pressing human health concern, the development of antibiotics against resistant strains of the Gram-positive streptococci. We previously characterized the first four of the mevalonate pathway enzymes of Enterococcus faecalis, and here characterize the fifth, phosphomevalonate kinase (E.C. 2.7.4.2). E. faecalis genomic DNA and the polymerase chain reaction were used to clone DNA thought to encode phosphomevalonate kinase into pET28b(+). Double-stranded DNA sequencing verified the sequence of the recombinant gene. The encoded N-terminal hexahistidine-tagged protein was expressed in Escherichia coli with induction by isopropylthiogalactoside and purified by Ni++ affinity chromatography, yield 20 mg protein per liter. Analysis of the purified protein by MALDI-TOF mass spectrometry established it as E. faecalis phosphomevalonate kinase. Analytical ultracentrifugation revealed that the kinase exists in solution primarily as a dimer. Assay for phosphomevalonate kinase activity used pyruvate kinase and lactate dehydrogenase to couple the formation of ADP to the oxidation of NADH. Optimal activity occurred at pH 8.0 and at 37°C. The activation energy was ~5.6 kcal/mol. Activity with Mn++, the preferred cation, was optimal at about 4 mM. Relative rates using different phosphoryl donors were 100 (ATP), 3.6 (GTP), 1.6 (TTP), and 0.4 (CTP). Km values were 0.17 mM for ATP and 0.19 mM for (R,S)-5-phosphomevalonate. The specific activity of the purified enzyme was 3.9 μmol substrate converted per minute per milligram protein. Applications to an immobilized enzyme bioreactor and to drug screening and design are discussed. PMID:15802646

  11. Eos Chaos Rocks

    Science.gov (United States)

    2006-01-01

    11 January 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows light-toned, layered rock outcrops in Eos Chaos, located near the east end of the Valles Marineris trough system. The outcrops occur in the form of a distinct, circular butte (upper half of image) and a high slope (lower half of image). The rocks might be sedimentary rocks, similar to those found elsewhere exposed in the Valles Marineris system and the chaotic terrain to the east of the region. Location near: 12.9oS, 49.5oW Image width: 3 km (1.9 mi) Illumination from: lower left Season: Southern Summer

  12. From Phosphosites to Kinases

    DEFF Research Database (Denmark)

    Munk, Stephanie; Refsgaard, Jan C; Olsen, Jesper V

    2016-01-01

    Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations...... sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available...

  13. Rock properties data base

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, R.; Gorski, B.; Gyenge, M.

    1991-03-01

    As mining companies proceed deeper and into areas whose stability is threatened by high and complex stress fields, the science of rock mechanics becomes invaluable in designing underground mine strata control programs. CANMET's Mining Research Laboratories division has compiled a summary of pre- and post-failure mechanical properties of rock types which were tested to provide design data. The 'Rock Properties Data Base' presents the results of these tests, and includes many rock types typical of Canadian mine environments. The data base also contains 'm' and 's' values determined using Hoek and Brown's failure criteria for both pre- and post-failure conditions. 7 refs., 3 tabs., 9 figs., 1 append.

  14. Eclogite facies rocks

    National Research Council Canada - National Science Library

    Carswell, D. A

    1990-01-01

    ... of eclogite evolution and genesis. The authors present a thorough treatment of the stability relations and geochemistry of these rocks, their intimate association with continental plate collision zones and suture zones...

  15. Rock kinoekraanil / Katrin Rajasaare

    Index Scriptorium Estoniae

    Rajasaare, Katrin

    2008-01-01

    7.-11. juulini kinos Sõprus toimuval filminädalal "Rock On Screen" ekraanile jõudvatest rockmuusikuid portreteerivatest filmidest "Lou Reed's Berlin", "The Future Is Unwritten: Joe Strummer", "Control: Joy Division", "Hurriganes", "Shlaager"

  16. Eclogite facies rocks

    National Research Council Canada - National Science Library

    Carswell, D. A

    1990-01-01

    .... This is the first volume to provide a coherent and comprehensive review of the conditions necessary for the formation of eclogites and eclogite facies rocks and assemblages, and a detailed account...

  17. Solid as a rock

    International Nuclear Information System (INIS)

    Pincus, H.J.

    1984-01-01

    Recent technologic developments have required a more comprehensive approach to the behavior of rock mass or rock substance plus discontinuities than was adequate previously. This work considers the inherent problems in such operations as the storage of hot or cold fluids in caverns and aquifers, underground storage of nuclear waste, underground recovery of heat from hydrocarbon fuels, tertiary recovery of oil by thermal methods, rapid excavation of large openings at shallow to great depths and in hostile environments, and retrofitting of large structures built on or in rock. The standardization of methods for determining rock properties is essential to all of the activities described, for use not only in design and construction but also in site selection and post-construction monitoring. Development of such standards is seen as a multidisciplinary effort

  18. Rock Equity Holdings, LLC

    Science.gov (United States)

    The EPA is providing notice of an Administrative Penalty Assessment in the form of an Expedited Storm Water Settlement Agreement against Rock Equity Holdings, LLC, for alleged violations at The Cove at Kettlestone/98th Street Reconstruction located at 3015

  19. Pop & rock / Berk Vaher

    Index Scriptorium Estoniae

    Vaher, Berk, 1975-

    2001-01-01

    Uute heliplaatide Redman "Malpractice", Brian Eno & Peter Schwalm "Popstars", Clawfinger "A Whole Lot of Nothing", Dario G "In Full Color", MLTR e. Michael Learns To Rock "Blue Night" lühitutvustused

  20. Basic rocks in Finland

    International Nuclear Information System (INIS)

    Piirainen, T.; Gehoer, S.; Iljina, M.; Kaerki, A.; Paakkola, J.; Vuollo, J.

    1992-10-01

    Basic igneous rocks, containing less than 52% SiO 2 , constitute an important part of the Finnish Archaean and Proterozoic crust. In the Archaean crust exist two units which contain the majority of the basic rocks. The Arcaean basic rocks are metavolcanics and situated in the Greenstone Belts of Eastern Finland. They are divided into two units. The greenstones of the lower one are tholeiites, komatiites and basaltic komatiites. The upper consists of bimodal series of volcanics and the basic rocks of which are Fe-tholeiites, basaltic komatiites and komatiites. Proterozoic basic rocks are divided into seven groups according to their ages. The Proterozoic igneous activity started by the volominous basic magmatism 2.44 Ga ago. During this stage formed the layered intrusions and related dykes in the Northern Finland. 2.2 Ga old basic rocks are situated at the margins of Karelian formations. 2.1 Ga aged Fe-tholeiitic magmatic activity is widespread in Eastern and Northern Finland. The basic rocks of 1.97 Ga age group are met within the Karelian Schist Belts as obducted ophiolite complexes but they occur also as tholeiitic diabase dykes cutting the Karelian schists and Archean basement. The intrusions and the volcanics of the 1.9 Ga old basic igneous activity are mostly encountered around the Granitoid Complex of Central Finland. Subjotnian, 1.6 Ga aged tholeiitic diabases are situated around the Rapakivi massifs of Southern Finland, and postjotnian, 1.2 Ga diabases in Western Finland where they form dykes cutting Svecofennian rocks

  1. Weathering of rock 'Ginger'

    Science.gov (United States)

    1997-01-01

    One of the more unusual rocks at the site is Ginger, located southeast of the lander. Parts of it have the reddest color of any material in view, whereas its rounded lobes are gray and relatively unweathered. These color differences are brought out in the inset, enhanced at the upper right. In the false color image at the lower right, the shape of the visible-wavelength spectrum (related to the abundance of weathered ferric iron minerals) is indicated by the hue of the rocks. Blue indicates relatively unweathered rocks. Typical soils and drift, which are heavily weathered, are shown in green and flesh tones. The very red color in the creases in the rock surface correspond to a crust of ferric minerals. The origin of the rock is uncertain; the ferric crust may have grown underneath the rock, or it may cement pebbles together into a conglomerate. Ginger will be a target of future super-resolution studies to better constrain its origin.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator. JPL is an operating division of the California Institute of Technology (Caltech).

  2. ROCK2 mediates the proliferation of pulmonary arterial endothelial cells induced by hypoxia in the development of pulmonary arterial hypertension

    OpenAIRE

    QIAO, FENG; ZOU, ZHITIAN; LIU, CHUNHUI; ZHU, XIAOFENG; WANG, XIAOQIANG; YANG, CHENGPENG; JIANG, TENGJIAO; CHEN, YING

    2016-01-01

    It has been reported that RhoA activation and Rho-kinase (ROCK) expression are increased in chronic hypoxic lungs, and the long-term inhibition of ROCK markedly improves the survival of patients with pulmonary arterial hypertension (PAH). However, whether Rho-kinase α (ROCK2) participates in regulation of the growth of pulmonary arterial endothelial cells (PAECs) remains unknown. The aim of the present study was to investigate the effect of hypoxia on the proliferation of PAECs and the role o...

  3. Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors.

    Science.gov (United States)

    Goodman, Krista B; Cui, Haifeng; Dowdell, Sarah E; Gaitanopoulos, Dimitri E; Ivy, Robert L; Sehon, Clark A; Stavenger, Robert A; Wang, Gren Z; Viet, Andrew Q; Xu, Weiwei; Ye, Guosen; Semus, Simon F; Evans, Christopher; Fries, Harvey E; Jolivette, Larry J; Kirkpatrick, Robert B; Dul, Edward; Khandekar, Sanjay S; Yi, Tracey; Jung, David K; Wright, Lois L; Smith, Gary K; Behm, David J; Bentley, Ross; Doe, Christopher P; Hu, Erding; Lee, Dennis

    2007-01-11

    Rho kinase (ROCK1) mediates vascular smooth muscle contraction and is a potential target for the treatment of hypertension and related disorders. Indazole amide 3 was identified as a potent and selective ROCK1 inhibitor but possessed poor oral bioavailability. Optimization of this lead resulted in the discovery of a series of dihydropyridones, exemplified by 13, with improved pharmacokinetic parameters relative to the initial lead. Indazole substitution played a critical role in decreasing clearance and improving oral bioavailability.

  4. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  5. Transporting radioactive rock

    International Nuclear Information System (INIS)

    Pearce, G.

    1990-01-01

    The case is made for exempting geological specimens from the IAEA Regulations for Safer Transport of Radioactive Materials. It is pointed out that many mineral collectors in Devon and Cornwall may be unwittingly infringing these regulations by taking naturally radioactive rocks and specimens containing uranium ores. Even if these collectors are aware that these rocks are radioactive, and many are not, few have the necessary equipment to monitor the activity levels. If the transport regulations were to be enforced alarm could be generated and the regulations devalued in case of an accident. The danger from a spill of rock specimens is negligible compared with an accident involving industrial or medical radioactive substances yet would require similar special treatment. (UK)

  6. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation.

    Science.gov (United States)

    Belkina, Natalya V; Liu, Yin; Hao, Jian-Jiang; Karasuyama, Hajime; Shaw, Stephen

    2009-03-24

    ERM (ezrin-radixin-moesin) proteins mediate linkage of actin cytoskeleton to plasma membrane in many cells. ERM activity is regulated in part by phosphorylation at a C-terminal threonine, but the identity of ERM kinases is unknown in lymphocytes and incompletely defined in other mammalian cells. Our studies show that lymphocyte-oriented kinase (LOK) is an ERM kinase in vitro and in vivo. Mass spectrometric analysis indicates LOK is abundant at the lymphocyte plasma membrane and immunofluorescence studies show LOK enrichment at the plasma membrane near ERM. In vitro peptide specificity analyses characterize LOK as a basophilic kinase whose optimal substrate sequence resembles the ERM site, including unusual preference for tyrosine at P-2. LOK's activity on moesin peptide and protein was comparable to reported ERM kinases ROCK and PKC but unlike them LOK displayed preferential specificity for moesin compared to traditional basophilic kinase substrates. Two genetic approaches demonstrate a role for LOK in ERM phosphorylation: cell transfection with LOK kinase domain augments ERM phosphorylation and lymphocytes from LOK knockout mice have >50% reduction in ERM phosphorylation. The findings on localization and specificity argue that LOK is a direct ERM kinase. The knockout mice have normal hematopoietic cell development but notably lymphocyte migration and polarization in response to chemokine are enhanced. These functional alterations fit the current understanding of the role of ERM phosphorylation in regulating cortical reorganization. Thus, these studies identify a new ERM kinase of importance in lymphocytes and confirm the role of ERM phosphorylation in regulating cell shape and motility.

  7. Geotechnical properties of rock

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, R.; Gorski, B.; Gyenge, M.

    1995-12-31

    The manual is a compilation of the geotechnical properties of many types of rock that are typical of Canadian mining environments. Included are values for density, porosity, compressive and shear wave velocity, uniaxial compressive strength, Young`s modulus, and Poisson`s ratio. The data base contains material constants that were determined using the Hoek and Brown failure criteria for both before and after failure conditions. 76 data sheets of rock properties in Canadian mines are included. 7 refs., 85 figs., 3 tabs.

  8. Rock engineering applications, 1991

    International Nuclear Information System (INIS)

    Franklin, J.A.; Dusseault, M.B.

    1991-01-01

    This book demonstrates how to apply the theories and principles of rock engineering to actual engineering and construction tasks. It features insights on geology for mining and tunnelling applications. It is practical resource that focuses on the latest technological innovation and examines up-to-date procedures used by engineers for coping with complex rock conditions. The authors also discuss question related to underground space, from design approaches to underground housing and storage. And they cover the monitoring of storage caverns for liquid and gaseous products or toxic and radioactive wastes

  9. Smart Rocking Armour Units

    OpenAIRE

    Hofland, B.; Arefin, Syed Shamsil; van der Lem, Cock; van gent, Marcel

    2018-01-01

    This paper describes a method to measure the rocking motion of lab-scale armour units. Sensors as found in mobile phones are used. These sensors, data-storage and battery are all embedded in the model units, such that they can be applied without wires attached to them. The technique is applied to double-layer units in order to compare the results to the existing knowledge for this type of armour layers. In contrast to previous research, the gyroscope reading is used to determine the (rocking)...

  10. Rock Hellsinki, Marketing Research

    OpenAIRE

    Todd, Roosa; Jalkanen, Katariina

    2013-01-01

    This paper is a qualitative research about rock and heavy metal music tourism in the capital city of Finland, Helsinki. As Helsinki can be considered the city of contrasts, the silent nature city mixed with urban activities, it is important to also use the potential of the loud rock and heavy metal music contrasting the silence. Finland is known abroad for bands such as HIM, Nightwish, Korpiklaani and Children of Bodom so it would make sense to utilize these in the tourism sector as well. The...

  11. Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia.

    Science.gov (United States)

    Roth Flach, Rachel J; Danai, Laura V; DiStefano, Marina T; Kelly, Mark; Menendez, Lorena Garcia; Jurczyk, Agata; Sharma, Rohit B; Jung, Dae Young; Kim, Jong Hun; Kim, Jason K; Bortell, Rita; Alonso, Laura C; Czech, Michael P

    2016-07-29

    Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance. Here, we report markedly reduced glucose-responsive plasma insulin and C-peptide levels in whole body Map4k4-depleted mice (M4K4 iKO) as well as an impaired first phase of insulin secretion from islets derived from M4K4 iKO mice ex vivo After long-term high fat diet (HFD), M4K4 iKO mice pancreata also displayed reduced β cell mass, fewer proliferating β cells and reduced islet-specific gene mRNA expression compared with controls, although insulin content was normal. Interestingly, the reduced plasma insulin in M4K4 iKO mice exposed to chronic (16 weeks) HFD was not observed in response to acute HFD challenge or short term treatment with the insulin receptor antagonist S961. Furthermore, the improved insulin sensitivity in obese M4K4 iKO mice was abrogated by high exogenous insulin over the course of a euglycemic clamp study, indicating that hypoinsulinemia promotes insulin sensitivity in chronically obese M4K4 iKO mice. These results demonstrate that protein kinase Map4k4 drives obesity-induced hyperinsulinemia and insulin resistance in part by promoting insulin secretion from β cells in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Dissecting the roles of ROCK isoforms in stress-induced cell detachment.

    Science.gov (United States)

    Shi, Jianjian; Surma, Michelle; Zhang, Lumin; Wei, Lei

    2013-05-15

    The homologous Rho kinases, ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant. Using mouse embryonic fibroblasts (MEFs) derived from ROCK1(-/-) and ROCK2(-/-) mice, we have recently reported that they play different roles in regulating doxorubicin-induced stress fiber disassembly and cell detachment: ROCK1 is involved in destabilizing the actin cytoskeleton and cell detachment, whereas ROCK2 is required for stabilizing the actin cytoskeleton and cell adhesion. Here, we present additional insights into the roles of ROCK1 and ROCK2 in regulating stress-induced impairment of cell-matrix and cell-cell adhesion. In response to doxorubicin, ROCK1(-/-) MEFs showed significant preservation of both focal adhesions and adherens junctions, while ROCK2(-/-) MEFs exhibited impaired focal adhesions but preserved adherens junctions compared with the wild-type MEFs. Additionally, inhibition of focal adhesion or adherens junction formations by chemical inhibitors abolished the anti-detachment effects of ROCK1 deletion. Finally, ROCK1(-/-) MEFs, but not ROCK2(-/-) MEFs, also exhibited preserved central stress fibers and reduced cell detachment in response to serum starvation. These results add new insights into a novel mechanism underlying the anti-detachment effects of ROCK1 deletion mediated by reduced peripheral actomyosin contraction and increased actin stabilization to promote cell-cell and cell-matrix adhesion. Our studies further support the differential roles of ROCK isoforms in regulating stress-induced loss of central stress fibers and focal adhesions as well as cell detachment.

  13. Regulation of Autophagy by Kinases

    International Nuclear Information System (INIS)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets

  14. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-06-09

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  15. Regulation of Autophagy by Kinases

    Science.gov (United States)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

    2011-01-01

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. PMID:24212825

  16. Regulation of Autophagy by Kinases

    Directory of Open Access Journals (Sweden)

    Savitha Sridharan

    2011-06-01

    Full Text Available Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  17. RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation.

    Science.gov (United States)

    Wu, Xiangbing; Walker, Chandler L; Lu, Qingbo; Wu, Wei; Eddelman, Daniel B; Parish, Jonathan M; Xu, Xiao-Ming

    2017-11-01

    Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A 2 (cPLA 2 ), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level. We found that co-administration of TNF-α and glutamate induced spinal neuron death, and activation of RhoA, Rho kinase and cPLA 2 . Inhibition of RhoA, Rho kinase and cPLA 2 significantly reduced TNF-α/glutamate-induced cell death by 33, 52 and 43 %, respectively (p < 0.001). Inhibition of RhoA and Rho kinase also significantly downregulated cPLA 2 activation by 66 and 60 %, respectively (p < 0.01). Furthermore, inhibition of RhoA and Rho kinase reduced the release of arachidonic acid, a downstream substrate of cPLA 2 . The immunofluorescence staining showed that ROCK 1 or ROCK 2 , two isoforms of Rho kinase, was co-localized with cPLA 2 in neuronal cytoplasm. Interestingly, co-immunoprecipitation (Co-IP) assay showed that ROCK 1 or ROCK 2 bonded directly with cPLA 2 and phospho-cPLA 2 . When the Rho kinase inhibitor Y27632 was applied in mice with T10 contusion injury, it significantly decreased cPLA 2 activation and expression and reduced injury-induced apoptosis at and close to the lesion site. Taken together, our results reveal a novel mechanism of RhoA/Rho kinase-mediated neuronal death through regulating cPLA 2 activation.

  18. A Rock Retrospective.

    Science.gov (United States)

    O'Grady, Terence J.

    1979-01-01

    The author offers an analysis of musical techniques found in the major rock trends of the 1960s. An annotated list of selected readings and a subject-indexed list of selected recordings are appended. This article is part of a theme issue on popular music. (Editor/SJL)

  19. Rock-hard coatings

    OpenAIRE

    Muller, M.

    2007-01-01

    Aircraft jet engines have to be able to withstand infernal conditions. Extreme heat and bitter cold tax coatings to the limit. Materials expert Dr Ir. Wim Sloof fits atoms together to develop rock-hard coatings. The latest invention in this field is known as ceramic matrix composites. Sloof has signed an agreement with a number of parties to investigate this material further.

  20. Fluids in metamorphic rocks

    NARCIS (Netherlands)

    Touret, J.L.R.

    2001-01-01

    Basic principles for the study of fluid inclusions in metamorphic rocks are reviewed and illustrated. A major problem relates to the number of inclusions, possibly formed on a wide range of P-T conditions, having also suffered, in most cases, extensive changes after initial trapping. The

  1. Rock-hard coatings

    NARCIS (Netherlands)

    Muller, M.

    2007-01-01

    Aircraft jet engines have to be able to withstand infernal conditions. Extreme heat and bitter cold tax coatings to the limit. Materials expert Dr Ir. Wim Sloof fits atoms together to develop rock-hard coatings. The latest invention in this field is known as ceramic matrix composites. Sloof has

  2. Northeast Church Rock Mine

    Science.gov (United States)

    Northeast Church Rock Mine, a former uranium mine 17 miles northeast of Gallup, NM in the Pinedale Chapter of the Navajo Nation. EPA is working with NNEPA to oversee cleanup work by United Nuclear Corporation, a company owned by General Electric (GE).

  3. Smart Rocking Armour Units

    NARCIS (Netherlands)

    Hofland, B.; Arefin, Syed Shamsil; van der Lem, Cock; van gent, Marcel

    2018-01-01

    This paper describes a method to measure the rocking motion of lab-scale armour units. Sensors as found in mobile phones are used. These sensors, data-storage and battery are all embedded in the model units, such that they can be applied without wires attached to them. The technique is applied to

  4. Teaching the Rock Cycle with Ease.

    Science.gov (United States)

    Bereki, Debra

    2000-01-01

    Describes a hands-on lesson for teaching high school students the concept of the rock cycle using sedimentary, metamorphic, and igneous rocks. Students use a rock cycle diagram to identify pairs of rocks. From the rock cycle, students explain on paper how their first rock became the second rock and vice versa. (PVD)

  5. For Those About to Rock : Naislaulajat rock-genressä

    OpenAIRE

    Herranen, Linda

    2015-01-01

    For those about to rock – naislaulajat rock-genressä antaa lukijalleen kokonaisvaltaisen käsityksen naisista rock-genressä: rockin historiasta, sukupuolittuneisuudesta, seksismistä, suomalaisten naislaulajien menestyksestä. Työn aineisto on koottu aihepiirin kirjallisuudesta ja alalla toimiville naislaulajille teetettyjen kyselyiden tuloksista. Lisäksi avaan omia kokemuksiani ja ajatuksiani, jotta näkökulma naisista rock-genressä tulisi esille mahdollisimman monipuolisesti. Ajatus aihees...

  6. Comparison of disposal concepts for rock salt and hard rock

    International Nuclear Information System (INIS)

    Papp, R.

    1998-01-01

    The study was carried out in the period 1994-1996. The goals were to prepare a draft on spent fuel disposal in hard rock and additionally a comparison with existing disposal concepts for rock salt. A cask for direct disposal of spent fuel and a repository for hard rock including a safeguards concept were conceptually designed. The results of the study confirm, that the early German decision to employ rock salt was reasonable. (orig.)

  7. Elastic Rock Heterogeneity Controls Brittle Rock Failure during Hydraulic Fracturing

    Science.gov (United States)

    Langenbruch, C.; Shapiro, S. A.

    2014-12-01

    For interpretation and inversion of microseismic data it is important to understand, which properties of the reservoir rock control the occurrence probability of brittle rock failure and associated seismicity during hydraulic stimulation. This is especially important, when inverting for key properties like permeability and fracture conductivity. Although it became accepted that seismic events are triggered by fluid flow and the resulting perturbation of the stress field in the reservoir rock, the magnitude of stress perturbations, capable of triggering failure in rocks, can be highly variable. The controlling physical mechanism of this variability is still under discussion. We compare the occurrence of microseismic events at the Cotton Valley gas field to elastic rock heterogeneity, obtained from measurements along the treatment wells. The heterogeneity is characterized by scale invariant fluctuations of elastic properties. We observe that the elastic heterogeneity of the rock formation controls the occurrence of brittle failure. In particular, we find that the density of events is increasing with the Brittleness Index (BI) of the rock, which is defined as a combination of Young's modulus and Poisson's ratio. We evaluate the physical meaning of the BI. By applying geomechanical investigations we characterize the influence of fluctuating elastic properties in rocks on the probability of brittle rock failure. Our analysis is based on the computation of stress fluctuations caused by elastic heterogeneity of rocks. We find that elastic rock heterogeneity causes stress fluctuations of significant magnitude. Moreover, the stress changes necessary to open and reactivate fractures in rocks are strongly related to fluctuations of elastic moduli. Our analysis gives a physical explanation to the observed relation between elastic heterogeneity of the rock formation and the occurrence of brittle failure during hydraulic reservoir stimulations. A crucial factor for understanding

  8. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten

    2010-01-01

    in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by tyrosine......Bacteria and Eukarya share essentially the same family of protein-serine/threonine kinases, also known as the Hanks-type kinases. However, when it comes to protein-tyrosine phosphorylation, bacteria seem to have gone their own way. Bacterial protein-tyrosine kinases (BY-kinases) are bacterial...... and highlighted their importance in bacterial physiology. Having no orthologues in Eukarya, BY-kinases are receiving a growing attention from the biomedical field, since they represent a particularly promising target for anti-bacterial drug design....

  9. Range sections as rock models for intensity rock scene segmentation

    CSIR Research Space (South Africa)

    Mkwelo, S

    2007-11-01

    Full Text Available This paper presents another approach to segmenting a scene of rocks on a conveyor belt for the purposes of measuring rock size. Rock size estimation instruments are used to monitor, optimize and control milling and crushing in the mining industry...

  10. Soil/Rock Properties Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Soil/Rock Properties LaboratoryLocation: Spokane SiteThe Soil/Rock Properties Laboratory is contained in the soils bay, a 4,700 sq. ft. facility that provides space...

  11. The Rho GTPase Effector ROCK Regulates Cyclin A, Cyclin D1, and p27Kip1 Levels by Distinct Mechanisms

    OpenAIRE

    Croft, Daniel R.; Olson, Michael F.

    2006-01-01

    The members of the Rho GTPase family are well known for their regulation of actin cytoskeletal structures. In addition, they influence progression through the cell cycle. The RhoA and RhoC proteins regulate numerous effector proteins, with a central and vital signaling role mediated by the ROCK I and ROCK II serine/threonine kinases. The requirement for ROCK function in the proliferation of numerous cell types has been revealed by studies utilizing ROCK-selective inhibitors such as Y-27632. H...

  12. Critical issues in soft rocks

    OpenAIRE

    Milton Assis Kanji

    2014-01-01

    This paper discusses several efforts made to study and investigate soft rocks, as well as their physico-mechanical characteristics recognized up to now, the problems in their sampling and testing, and the possibility of its reproduction through artificially made soft rocks. The problems in utilizing current and widespread classification systems to some types of weak rocks are also discussed, as well as other problems related to them. Some examples of engineering works in soft rock or in soft ...

  13. Isotope shifting capacity of rock

    International Nuclear Information System (INIS)

    Blattner, P.; Department of Scientific and Industrial Research, Lower Hutt

    1980-01-01

    Any oxygen isotope shifted rock volume exactly defines a past throughput of water. An expression is derived that relates the throughput of an open system to the isotope shift of reservoir rock and present-day output. The small isotope shift of Ngawha reservoir rock and the small, high delta oxygen-18 output are best accounted for by a magmatic water source

  14. Rock burst governance of working face under igneous rock

    Science.gov (United States)

    Chang, Zhenxing; Yu, Yue

    2017-01-01

    As a typical failure phenomenon, rock burst occurs in many mines. It can not only cause the working face to cease production, but also cause serious damage to production equipment, and even result in casualties. To explore how to govern rock burst of working face under igneous rock, the 10416 working face in some mine is taken as engineering background. The supports damaged extensively and rock burst took place when the working face advanced. This paper establishes the mechanical model and conducts theoretical analysis and calculation to predict the fracture and migration mechanism and energy release of the thick hard igneous rock above the working face, and to obtain the advancing distance of the working face when the igneous rock fractures and critical value of the energy when rock burst occurs. Based on the specific conditions of the mine, this paper put forward three kinds of governance measures, which are borehole pressure relief, coal seam water injection and blasting pressure relief.

  15. Uranium in alkaline rocks

    International Nuclear Information System (INIS)

    Murphy, M.; Wollenberg, H.; Strisower, B.; Bowman, H.; Flexser, S.; Carmichael, I.

    1978-04-01

    Geologic and geochemical criteria were developed for the occurrence of economic uranium deposits in alkaline igneous rocks. A literature search, a limited chemical analytical program, and visits to three prominent alkaline-rock localities (Ilimaussaq, Greenland; Pocos de Caldas, Brazil; and Powderhorn, Colorado) were made to establish criteria to determine if a site had some uranium resource potential. From the literature, four alkaline-intrusive occurrences of differing character were identified as type-localities for uranium mineralization, and the important aspects of these localities were described. These characteristics were used to categorize and evaluate U.S. occurrences. The literature search disclosed 69 U.S. sites, encompassing nepheline syenite, alkaline granite, and carbonatite. It was possible to compare two-thirds of these sites to the type localities. A ranking system identified ten of the sites as most likely to have uranium resource potential

  16. Rock solidification method

    International Nuclear Information System (INIS)

    Nakaya, Iwao; Murakami, Tadashi; Miyake, Takafumi; Funakoshi, Toshio; Inagaki, Yuzo; Hashimoto, Yasuhide.

    1985-01-01

    Purpose: To convert radioactive wastes into the final state for storage (artificial rocks) in a short period of time. Method: Radioactive burnable wastes such as spent papers, cloths and oils and activated carbons are burnt into ashes in a burning furnace, while radioactive liquid wastes such as liquid wastes of boric acid, exhausted cleaning water and decontaminating liquid wastes are powderized in a drying furnace or calcining furnace. These powders are joined with silicates as such as white clay, silica and glass powder and a liquid alkali such as NaOH or Ca(OH) 2 and transferred to a solidifying vessel. Then, the vessel is set to a hydrothermal reactor, heated and pressurized, then taken out about 20 min after and tightly sealed. In this way, radioactive wastes are converted through the hydrothermal reactions into aqueous rock stable for a long period of time to obtain solidification products insoluble to water and with an extremely low leaching rate. (Ikeda, J.)

  17. Uranium in alkaline rocks

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M.; Wollenberg, H.; Strisower, B.; Bowman, H.; Flexser, S.; Carmichael, I.

    1978-04-01

    Geologic and geochemical criteria were developed for the occurrence of economic uranium deposits in alkaline igneous rocks. A literature search, a limited chemical analytical program, and visits to three prominent alkaline-rock localities (Ilimaussaq, Greenland; Pocos de Caldas, Brazil; and Powderhorn, Colorado) were made to establish criteria to determine if a site had some uranium resource potential. From the literature, four alkaline-intrusive occurrences of differing character were identified as type-localities for uranium mineralization, and the important aspects of these localities were described. These characteristics were used to categorize and evaluate U.S. occurrences. The literature search disclosed 69 U.S. sites, encompassing nepheline syenite, alkaline granite, and carbonatite. It was possible to compare two-thirds of these sites to the type localities. A ranking system identified ten of the sites as most likely to have uranium resource potential.

  18. Rock and mineral magnetism

    CERN Document Server

    O’Reilly, W

    1984-01-01

    The past two decades have witnessed a revolution in the earth sciences. The quantitative, instrument-based measurements and physical models of. geophysics, together with advances in technology, have radically transformed the way in which the Earth, and especially its crust, is described. The study of the magnetism of the rocks of the Earth's crust has played a major part in this transformation. Rocks, or more specifically their constituent magnetic minerals, can be regarded as a measuring instrument provided by nature, which can be employed in the service of the earth sciences. Thus magnetic minerals are a recording magnetometer; a goniometer or protractor, recording the directions of flows, fields and forces; a clock; a recording thermometer; a position recorder; astrain gauge; an instrument for geo­ logical surveying; a tracer in climatology and hydrology; a tool in petrology. No instrument is linear, or free from noise and systematic errors, and the performance of nature's instrument must be assessed and ...

  19. Aram Chaos Rocks

    Science.gov (United States)

    2005-01-01

    8 September 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows outcrops of light-toned, sedimentary rock among darker-toned mesas in Aram Chaos. Dark, windblown megaripples -- large ripples -- are also present at this location. Location near: 3.0oN, 21.6oW Image width: width: 3 km (1.9 mi) Illumination from: lower left Season: Northern Autumn

  20. Deformations of fractured rock

    International Nuclear Information System (INIS)

    Stephansson, O.

    1977-09-01

    Results of the DBM and FEM analysis in this study indicate that a suitable rock mass for repository of radioactive waste should be moderately jointed (about 1 joint/m 2 ) and surrounded by shear zones of the first order. This allowes for a gentle and flexible deformation under tectonic stresses and prevent the development of large cross-cutting failures in the repository area. (author)

  1. Physical modeling of rock

    International Nuclear Information System (INIS)

    Cheney, J.A.

    1981-01-01

    The problems of statisfying similarity between a physical model and the prototype in rock wherein fissures and cracks place a role in physical behavior is explored. The need for models of large physical dimensions is explained but also testing of models of the same prototype over a wide range of scales is needed to ascertain the influence of lack of similitude of particular parameters between prototype and model. A large capacity centrifuge would be useful in that respect

  2. Rock disposal problems identified

    Energy Technology Data Exchange (ETDEWEB)

    Knox, R

    1978-06-01

    Mathematical models are the only way of examining the return of radioactivity from nuclear waste to the environment over long periods of time. Work in Britain has helped identify areas where more basic data is required, but initial results look very promising for final disposal of high level waste in hard rock repositories. A report by the National Radiological Protection Board of a recent study, is examined.

  3. Rock pushing and sampling under rocks on Mars

    Science.gov (United States)

    Moore, H.J.; Liebes, S.; Crouch, D.S.; Clark, L.V.

    1978-01-01

    Viking Lander 2 acquired samples on Mars from beneath two rocks, where living organisms and organic molecules would be protected from ultraviolet radiation. Selection of rocks to be moved was based on scientific and engineering considerations, including rock size, rock shape, burial depth, and location in a sample field. Rock locations and topography were established using the computerized interactive video-stereophotogrammetric system and plotted on vertical profiles and in plan view. Sampler commands were developed and tested on Earth using a full-size lander and surface mock-up. The use of power by the sampler motor correlates with rock movements, which were by plowing, skidding, and rolling. Provenance of the samples was determined by measurements and interpretation of pictures and positions of the sampler arm. Analytical results demonstrate that the samples were, in fact, from beneath the rocks. Results from the Gas Chromatograph-Mass Spectrometer of the Molecular Analysis experiment and the Gas Exchange instrument of the Biology experiment indicate that more adsorbed(?) water occurs in samples under rocks than in samples exposed to the sun. This is consistent with terrestrial arid environments, where more moisture occurs in near-surface soil un- der rocks than in surrounding soil because the net heat flow is toward the soil beneath the rock and the rock cap inhibits evaporation. Inorganic analyses show that samples of soil from under the rocks have significantly less iron than soil exposed to the sun. The scientific significance of analyses of samples under the rocks is only partly evaluated, but some facts are clear. Detectable quantities of martian organic molecules were not found in the sample from under a rock by the Molecular Analysis experiment. The Biology experiments did not find definitive evidence for Earth-like living organisms in their sample. Significant amounts of adsorbed water may be present in the martian regolith. The response of the soil

  4. The Rock Characterization Facility

    International Nuclear Information System (INIS)

    Holmes, J.

    1994-01-01

    In 1989, UK Nirex began a programme of surface-based characterization of the geology and hydrogeology of a site at Sellafield to evaluate its suitability to host a deep repository for radioactive waste. The next major stage in site characterization will be the construction and operation of a Rock Characterization Facility (RCF). It will be designed to provide rock characterization information and scope for model validation to permit firmer assessment of long-term safety. It will also provide information needed to decide the detailed location, design and orientation of a repository and to inform repository construction methods. A three-phase programme is planned for the RCF. During each phase, testwork will steadily improve our geological, hydrogeological and geotechnical understanding of the site. The first phase will involve sinking two shafts. That will be preceded by the establishment of a network of monitoring boreholes to ensure that the impact of shaft sinking can be measured. This will provide valuable data for model validation. In phase two, initial galleries will be excavated, probably at a depth of 650 m below Ordnance datum, which will host a comprehensive suite of experiments. These galleries will be extended in phase three to permit access to most of the rock volume that would host the repository. (Author)

  5. Rock in Rio: forever young

    Directory of Open Access Journals (Sweden)

    Ricardo Ferreira Freitas

    2014-12-01

    Full Text Available The purpose of this article is to discuss the role of Rock in Rio: The Musical, as herald of megafestival Rock in Rio. Driven by the success that musicals have reached in Brazil, we believe that the design of this spectacle of music, dance and staging renews the brand of the rock festival, once it adds the force of young and healthy bodies to its concept. Moreover, the musical provides Rock in Rio with some distance from the controversal trilogy of sex, drugs and rock and roll, a strong mark of past festivals around the world. Thus, the musical expands the possibilities of growth for the brand.

  6. Development of artificial soft rock

    International Nuclear Information System (INIS)

    Kishi, Kiyoshi

    1995-01-01

    When foundation base rocks are deeper than the level of installing structures or there exist weathered rocks and crushed rocks in a part of base rocks, often sound artificial base rocks are made by substituting the part with concrete. But in the construction of Kashiwazaki Kariwa Nuclear Power Station of Tokyo Electric Power Co., Inc., the foundation base rocks consist of mudstone, and the stiffness of concrete is large as compared with the surrounding base rocks. As the quality of the substituting material, the nearly same stiffness as that of the surrounding soft rocks and long term stability are suitable, and the excellent workability and economical efficiency are required, therefore, artificial soft rocks were developed. As the substituting material, the soil mortar that can obtain the physical property values in stable form, which are similar to those of Nishiyama mudstone, was selected. The mechanism of its hardening and the long term stability, and the manufacturing plant are reported. As for its application to the base rocks of Kashiwazaki Kariwa Nuclear Power Station, the verification test at the site and the application to the base rocks for No. 7 plant reactor building and other places are described. (K.I.)

  7. Hydrological characteristics of Japanese rock

    International Nuclear Information System (INIS)

    Ijiri, Yuji; Sawada, Atsushi; Akahori, Kuniaki

    1999-11-01

    It is crucial to evaluate the hydrogeological characteristics of rock in Japan in order to assess the performance of geosphere. This report summarizes the hydrogeological characteristics of various rock types obtained from broad literature surveys and the fields experiments at the Kamaishi mine in northern Japan and at the Tono mine in central Japan. It is found that the hydraulic conductivity of rock mass ranges from 10 -9 m/s to 10 -8 m/s, whereas the hydraulic conductivity of fault zone ranges from 10 -9 m/s to 10 -3 m/s. It is also found that the hydraulic conductivity tends to decrease with depth. Therefore, the hydraulic conductivity of rock mass at the depth of a repository will be smaller than above values. From the investigations at outcrops and galleries throughout the country, fractures are observed as potential pathways in all rock types. All kinds of crystalline rocks and pre-Neogene sedimentary rocks are classified as fractured media where fracture flow is dominant. Among these rocks, granitic rock is considered the archetype fractured media. On the other hand, andesite, tuff and Neogene sedimentary rocks are considered as intermediate between fractured media and porous media where flow in fractures as well as in rock matrix are significant. (author)

  8. Grinding into Soft, Powdery Rock

    Science.gov (United States)

    2004-01-01

    This hole in a rock dubbed 'Clovis' is the deepest hole drilled so far in any rock on Mars. NASA's Mars Exploration Rover Spirit captured this view with its microscopic imager on martian sol 217 (Aug. 12, 2004) after drilling 8.9 millimeters (0.35 inch) into the rock with its rock abrasion tool. The view is a mosaic of four frames taken by the microscopic imager. The hole is 4.5 centimeters (1.8 inches) in diameter. Clovis is key to a developing story about environmental change on Mars, not only because it is among the softest rocks encountered so far in Gusev Crater, but also because it contains mineral alterations that extend relatively deep beneath its surface. In fact, as evidenced by its fairly crumbly texture, it is possibly the most highly altered volcanic rock ever studied on Mars. Scientific analysis shows that the rock contains higher levels of the elements sulfur, chlorine, and bromine than are normally encountered in basaltic rocks, such as a rock dubbed 'Humphrey' that Spirit encountered two months after arriving on Mars. Humphrey showed elevated levels of sulfur, chlorine, and bromine only in the outermost 2 millimeters (less than 0.1 inch) of its surface. Clovis shows elevated levels of the same elements along with the associated softness of the rock within a borehole that is 4 times as deep. Scientists hope to compare Clovis to other, less-altered rocks in the vicinity to assess what sort of water-based processes altered the rock. Hypotheses include transport of sulfur, chlorine, and bromine in water vapor in volcanic gases; hydrothermal circulation (flow of volcanically heated water through rock); or saturation in a briny soup containing the same elements. In this image, very fine-grained material from the rock has clumped together by electrostatic attraction and fallen into the borehole. NASA/JPL/Cornell/USGS

  9. Receptor-interacting protein (RIP) kinase family

    OpenAIRE

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, incl...

  10. ROCK inhibition in models of neurodegeneration and its potential for clinical translation.

    Science.gov (United States)

    Koch, Jan Christoph; Tatenhorst, Lars; Roser, Anna-Elisa; Saal, Kim-Ann; Tönges, Lars; Lingor, Paul

    2018-04-03

    Neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis are affecting a rapidly increasing population worldwide. While common pathomechanisms such as protein aggregation, axonal degeneration, dysfunction of protein clearing and an altered immune response have been characterized, no disease-modifying therapies have been developed so far. Interestingly, a significant involvement of the Rho kinase (ROCK) signaling pathway has been described in all of these mechanisms making it a promising target for new therapeutic approaches. In this article, we first review current knowledge of the involvement of ROCK in neurodegenerative disorders and the utility of its inhibition as a disease-modifying therapy in different neurodegenerative disorders. After a detailed description of the biochemical characteristics of ROCK and its molecular interactors, differences of ROCK-expression under physiological and pathological conditions are compared. Next, different pharmacological and molecular-genetic strategies to inhibit ROCK-function are discussed, focusing on pharmacological ROCK-inhibitors. The role of the ROCK-pathway in cellular processes that are central in neurodegenerative disorders pathology like axonal degeneration, autophagy, synaptic and glial function is explained in detail. Finally, all available data on ROCK-inhibition in different animal models of neurodegenerative disorders is reviewed and first approaches for translation into human patients are discussed. Taken together, there is now extensive evidence from preclinical studies in several neurodegenerative disorders that characterize ROCK as a promising drug target for further translational research in neurodegenerative disorders. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells.

    Science.gov (United States)

    Inaba, Nobuharu; Ishizawa, Sho; Kimura, Masaki; Fujioka, Kouki; Watanabe, Michiko; Shibasaki, Toshiaki; Manome, Yoshinobu

    2010-09-01

    Malignant glioma is one of the most intractable diseases in the human body. Rho-kinase (ROCK) is overexpressed and has been proposed as the main cause for the refractoriness of the disease. Since efficacious treatment is required, this study investigated the effect of inhibition of ROCK isoforms. The short hairpin RNA transcription vector was transfected into the RT2 rat glioma cell line and the characteristics of the cells were investigated. The effect of nimustine hydrochloride (ACNU) anti-neoplastic agent on cells was also measured. Inhibition of ROCK isoforms did not alter cell growth. Cell cycle analysis revealed that ROCK1 down-regulation reduced the G(0) phase population and ROCK2 down-regulation reduced the G(2)/M phase population. When ROCK1-down-regulated cells were exposed to ACNU, they demonstrated susceptibility to the agent. The roles of ROCK1 and ROCK2 may be different in glioma cells. Furthermore, the combination of ROCK1 down-regulation and an anti-neoplastic agent may be useful for the therapy of malignant glioma.

  12. Rock mechanics for hard rock nuclear waste repositories

    International Nuclear Information System (INIS)

    Heuze, F.E.

    1981-09-01

    The mined geologic burial of high level nuclear waste is now the favored option for disposal. The US National Waste Terminal Storage Program designed to achieve this disposal includes an extensive rock mechanics component related to the design of the wastes repositories. The plan currently considers five candidate rock types. This paper deals with the three hard rocks among them: basalt, granite, and tuff. Their behavior is governed by geological discontinuities. Salt and shale, which exhibit behavior closer to that of a continuum, are not considered here. This paper discusses both the generic rock mechanics R and D, which are required for repository design, as well as examples of projects related to hard rock waste storage. The examples include programs in basalt (Hanford/Washington), in granitic rocks (Climax/Nevada Test Site, Idaho Springs/Colorado, Pinawa/Canada, Oracle/Arizona, and Stripa/Sweden), and in tuff

  13. Rock stress investigations

    International Nuclear Information System (INIS)

    Pahl, A.; Heusermann, St.; Braeuer, V.; Gloeggler, W.

    1989-04-01

    On the research project 'Rock Stress Mesurements' the BGR has developed and tested several methods for use in boreholes at a depth of 200 m. Indirect stress measurements using overcoring methods with BGR-probes and CSIR-triaxial cells as well as direct stress measurements using the hydraulic-fracturing method were made. To determine in-situ rock deformation behavior borehole deformation tests, using a BGR-dilatometer, were performed. Two types of the BGR-probe were applied: a four-component-probe to determine horizontal stresses and a five-component-probe to determine a quasi three-dimensional stress field. The first time a computer for data processing was installed in the borehole together with the BGR-probe. Laboratory tests on low cylinders were made to study the stress-deformation behavior. To validate and to interprete the measurement results some test methods were modelled using the finite-element method. The dilatometer-tests yielded high values of Young's modulus, whereas laboratory tests showed lower values with a distinct deformation anisotropy. Stress measurements with the BGR-probe yielded horizontal stresses being higher than the theoretical overburden pressure. These results are comparable to the results of the hydraulic fracturing tests, whereas stresses obtained with CSIR-triaxial cells are lower. The detailed geological mapping of the borehole indicated relationships between stress and geology. With regard to borehole depth different zones of rock structure joint frequency, joint orientation, and orientation of microfissures as well as stress magnitude, stress direction, and degree of deformation anisotropy could be distinguished. (author) 4 tabs., 76 figs., 31 refs

  14. A smart rock

    Science.gov (United States)

    Pressel, Phil

    2014-12-01

    This project was to design and build a protective weapon for a group of associations that believed in aliens and UFO's. They collected enough contributions from societies and individuals to be able to sponsor and totally fund the design, fabrication and testing of this equipment. The location of this facility is classified. It also eventually was redesigned by the Quartus Engineering Company for use at a major amusement park as a "shoot at targets facility." The challenge of this project was to design a "smart rock," namely an infrared bullet (the size of a gallon can of paint) that could be shot from the ground to intercept a UFO or any incoming suspicious item heading towards the earth. Some of the challenges to design this weapon were to feed cryogenic helium at 5 degrees Kelvin from an inair environment through a unique rotary coupling and air-vacuum seal while spinning the bullet at 1500 rpm and maintain its dynamic stability (wobble) about its spin axis to less than 10 micro-radians (2 arc seconds) while it operated in a vacuum. Precision optics monitored the dynamic motion of the "smart rock."

  15. Rock critics as 'Mouldy Modernists'

    Directory of Open Access Journals (Sweden)

    Becky Shepherd

    2011-08-01

    Full Text Available Contemporary rock criticism appears to be firmly tied to the past. The specialist music press valorise rock music of the 1960s and 1970s, and new emerging artists are championed for their ‘retro’ sounding music by journalists who compare the sound of these new artists with those included in the established ‘canon’ of rock music. This article examines the narrative tropes of authenticity and nostalgia that frame the retrospective focus of this contemporary rock writing, and most significantly, the maintenance of the rock canon within contemporary popular culture. The article concludes by suggesting that while contemporary rock criticism is predominately characterised by nostalgia, this nostalgia is not simply a passive romanticism of the past. Rather, this nostalgia fuels a process of active recontextualisation within contemporary popular culture.

  16. AGC kinases, mechanisms of regulation ‎and innovative drug development.

    Science.gov (United States)

    Leroux, Alejandro E; Schulze, Jörg O; Biondi, Ricardo M

    2018-02-01

    The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation. In the present review, we update the knowledge of the mechanisms of regulation of different AGC kinases. The conformation of the catalytic domain of many AGC kinases is regulated allosterically through the modulation of the conformation of a regulatory site on the small lobe of the kinase domain, the PIF-pocket. The PIF-pocket acts like an ON-OFF switch in AGC kinases with different modes of regulation, i.e. PDK1, PKB/Akt, LATS and Aurora kinases. In this review, we make emphasis on how the knowledge of the molecular mechanisms of regulation can guide the discovery and development of small allosteric modulators. Molecular probes stabilizing the PIF-pocket in the active conformation are activators, while compounds stabilizing the disrupted site are allosteric inhibitors. One challenge for the rational development of allosteric modulators is the lack of complete structural information of the inhibited forms of full-length AGC kinases. On the other hand, we suggest that the available information derived from molecular biology and biochemical studies can already guide screening strategies for the identification of innovative mode of action molecular probes and the development of selective allosteric drugs for the treatment of human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Rock.XML - Towards a library of rock physics models

    Science.gov (United States)

    Jensen, Erling Hugo; Hauge, Ragnar; Ulvmoen, Marit; Johansen, Tor Arne; Drottning, Åsmund

    2016-08-01

    Rock physics modelling provides tools for correlating physical properties of rocks and their constituents to the geophysical observations we measure on a larger scale. Many different theoretical and empirical models exist, to cover the range of different types of rocks. However, upon reviewing these, we see that they are all built around a few main concepts. Based on this observation, we propose a format for digitally storing the specifications for rock physics models which we have named Rock.XML. It does not only contain data about the various constituents, but also the theories and how they are used to combine these building blocks to make a representative model for a particular rock. The format is based on the Extensible Markup Language XML, making it flexible enough to handle complex models as well as scalable towards extending it with new theories and models. This technology has great advantages as far as documenting and exchanging models in an unambiguous way between people and between software. Rock.XML can become a platform for creating a library of rock physics models; making them more accessible to everyone.

  18. Rocks under pressure

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-05-01

    Physicists have used nuclear magnetic resonance to investigate the destructive effects of the crystallization of salt. Salt-weathering is one of the main causes of rock disintegration in nature, particularly in deserts, polar regions and along coastlines. However, it is also a very widespread cause of damage to man-made constructions. Bridges, for example, are attacked by de-icing salts, and cities such as Bahrain, Abu Dhabi and Adelaide are affected by rising damp from high ground-water levels. Indeed, many examples of cultural heritage, including the Islamic sites of Bokhara and Petra in Jordan and the Sphinx in Egypt, may ultimately be destroyed due to the effects of salt-weathering. Now Lourens Rijniers and colleagues at Eindhoven University in the Netherlands have developed a way to observe the solubility of various salts inside porous materials directly (Phys. Rev. Lett. 94 075503). (U.K.)

  19. Rock the Globe

    CERN Multimedia

    Laëtitia Pedroso

    2010-01-01

    Created in 2005, the Swiss rock band "Wind of Change" is now candidate for the Eurovision Song Contest 2011 with a new song " Night & Light " with the music video filmed at CERN.   With over 20 gigs under their belt and two albums already released, the five members of the band (Alex Büchi, vocals; Arthur Spierer, drums; David Gantner, bass; Romain Mage and Yannick Gaudy, guitar) continue to excite audiences. For their latest composition "Night & Light", the group filmed their music video in the Globe of Science and Innovation. Winning the Eurovision contest would be a springboard in their artistic career for these young musicians. The selection results will be available December 11, 2010.      

  20. Electrochemistry of lunar rocks

    Science.gov (United States)

    Lindstrom, D. J.; Haskin, L. A.

    1979-01-01

    Electrolysis of silicate melts has been shown to be an effective means of producing metals from common silicate materials. No fluxing agents need be added to the melts. From solution in melts of diopside (CaMgSi2O6) composition, the elements Si, Ti, Ni, and Fe have been reduced to their metallic states. Platinum is a satisfactory anode material, but other cathode materials are needed. Electrolysis of compositional analogs of lunar rocks initially produces iron metal at the cathode and oxygen gas at the anode. Utilizing mainly heat and electricity which are readily available from sunlight, direct electrolysis is capable of producing useful metals from common feedstocks without the need for expendable chemicals. This simple process and the products obtained from it deserve further study for use in materials processing in space.

  1. Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells.

    Directory of Open Access Journals (Sweden)

    Roman J Krawetz

    Full Text Available The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK play pivotal roles in cell migration, apoptosis (membrane blebbing, cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the

  2. Rock Art in Kurdistan Iran

    Directory of Open Access Journals (Sweden)

    Jamal Lahafian

    2013-12-01

    Full Text Available Kurdistan, with great potential and prehistoric resources, has numerous petroglyphs in different areas of the province. During the last 14 years of extensive field study, more than 30 sites of rock art have been identified and introduced by the author. In this article, we summarize these rock art areas in Iranian Kurdistan.

  3. Rockin' around the Rock Cycle

    Science.gov (United States)

    Frack, Susan; Blanchard, Scott Alan

    2005-01-01

    In this activity students will simulate how sedimentary rocks can be changed into metamorphic rocks by intense pressure. The materials needed are two small pieces of white bread, one piece of wheat bread, and one piece of a dark bread (such as pumpernickel or dark rye) per student, two pieces of waxed paper, scissors, a ruler, and heavy books.…

  4. 'Mister Badger' Pushing Mars Rock

    Science.gov (United States)

    1976-01-01

    Viking's soil sampler collector arm successfully pushed a rock on the surface of Mars during the afternoon of Friday, October 8. The irregular-shaped rock was pushed several inches by the Lander's collector arm, which displaced the rock to the left of its original position, leaving it cocked slightly upward. Photographs and other information verified the successful rock push. Photo at left shows the soil sampler's collector head pushing against the rock, named 'Mister Badger' by flight controllers. Photo at right shows the displaced rock and the depression whence it came. Part of the soil displacement was caused by the collector s backhoe. A soil sample will be taken from the site Monday night, October 11. It will then be delivered to Viking s organic chemistry instrument for a series of analyses during the next few weeks. The sample is being sought from beneath a rock because scientists believe that, if there are life forms on Mars, they may seek rocks as shelter from the Sun s intense ultraviolet radiation.

  5. Rock suitability classification RSC 2012

    Energy Technology Data Exchange (ETDEWEB)

    McEwen, T. (ed.) [McEwen Consulting, Leicester (United Kingdom); Kapyaho, A. [Geological Survey of Finland, Espoo (Finland); Hella, P. [Saanio and Riekkola, Helsinki (Finland); Aro, S.; Kosunen, P.; Mattila, J.; Pere, T.

    2012-12-15

    This report presents Posiva's Rock Suitability Classification (RSC) system, developed for locating suitable rock volumes for repository design and construction. The RSC system comprises both the revised rock suitability criteria and the procedure for the suitability classification during the construction of the repository. The aim of the classification is to avoid such features of the host rock that may be detrimental to the favourable conditions within the repository, either initially or in the long term. This report also discusses the implications of applying the RSC system for the fulfilment of the regulatory requirements concerning the host rock as a natural barrier and the site's overall suitability for hosting a final repository of spent nuclear fuel.

  6. Rock suitability classification RSC 2012

    International Nuclear Information System (INIS)

    McEwen, T.; Kapyaho, A.; Hella, P.; Aro, S.; Kosunen, P.; Mattila, J.; Pere, T.

    2012-12-01

    This report presents Posiva's Rock Suitability Classification (RSC) system, developed for locating suitable rock volumes for repository design and construction. The RSC system comprises both the revised rock suitability criteria and the procedure for the suitability classification during the construction of the repository. The aim of the classification is to avoid such features of the host rock that may be detrimental to the favourable conditions within the repository, either initially or in the long term. This report also discusses the implications of applying the RSC system for the fulfilment of the regulatory requirements concerning the host rock as a natural barrier and the site's overall suitability for hosting a final repository of spent nuclear fuel

  7. Rock strength under explosive loading

    International Nuclear Information System (INIS)

    Rimer, N.; Proffer, W.

    1993-01-01

    This presentation emphasizes the importance of a detailed description of the nonlinear deviatoric (strength) response of the surrounding rock in the numerical simulation of underground nuclear explosion phenomenology to the late times needed for test ban monitoring applications. We will show how numerical simulations which match ground motion measurements in volcanic tuffs and in granite use the strength values obtained from laboratory measurements on small core samples of these rocks but also require much lower strength values after the ground motion has interacted with the rock. The underlying physical mechanisms for the implied strength reduction are not yet well understood, and in fact may depend on the particular rock type. However, constitutive models for shock damage and/or effective stress have been used successfully at S-Cubed in both the Geophysics Program (primarily for DARPA) and the Containment Support Program (for DNA) to simulate late time ground motions measured at NTS in many different rock types

  8. Targeting ROCK activity to disrupt and prime pancreatic cancer for chemotherapy.

    Science.gov (United States)

    Vennin, Claire; Rath, Nicola; Pajic, Marina; Olson, Michael F; Timpson, Paul

    2017-10-03

    Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease; the identification of novel targets and development of effective treatment strategies are urgently needed to improve patient outcomes. Remodeling of the pancreatic stroma occurs during PDAC development, which drives disease progression and impairs responses to therapy. The actomyosin regulatory ROCK1 and ROCK2 kinases govern cell motility and contractility, and have been suggested to be potential targets for cancer therapy, particularly to reduce the metastatic spread of tumor cells. However, ROCK inhibitors are not currently used for cancer patient treatment, largely due to the overwhelming challenge faced in the development of anti-metastatic drugs, and a lack of clarity as to the cancer types most likely to benefit from ROCK inhibitor therapy. In 2 recent publications, we discovered that ROCK1 and ROCK2 expression were increased in PDAC, and that increased ROCK activity was associated with reduced survival and PDAC progression by enabling extracellular matrix (ECM) remodeling and invasive growth of pancreatic cancer cells. We also used intravital imaging to optimize ROCK inhibition using the pharmacological ROCK inhibitor fasudil (HA-1077), and demonstrated that short-term ROCK targeting, or 'priming', improved chemotherapy efficacy, disrupted cancer cell collective movement, and impaired metastasis. This body of work strongly indicates that the use of ROCK inhibitors in pancreatic cancer therapy as 'priming' agents warrants further consideration, and provides insights as to how transient mechanical manipulation, or fine-tuning the ECM, rather than chronic stromal ablation might be beneficial for improving chemotherapeutic efficacy in the treatment of this deadly disease.

  9. They will rock you!

    CERN Multimedia

    Anaïs Schaeffer

    2013-01-01

    On 30 September, CERN will be the venue for one of the most prestigious events of the year: the concert for the Bosons&More event, the Organization’s celebration of the remarkable performance of the LHC and all its technical systems, as well as the recent fundamental discoveries. Topping the bill will be the Orchestre de la Suisse Romande, the CERN Choir, the Zürcher Sing-Akademie and the Alan Parsons Live Project rock group, who have joined forces to create an unforgettable evening’s entertainment.   The Orchestre de la Suisse Romande, directed by Maestro Neeme Järvi, artistic and musical director of the OSR. (Image: Grégory Maillot). >>> From the Orchestre de la Suisse Romande… Henk Swinnen, General Manager of the Orchestre de la Suisse Romande (OSR), answers some questions for the CERN Bulletin, just a few days before the event. How did this project come about? When CERN invited us to take part in the B...

  10. Rock salt constitutive modeling

    International Nuclear Information System (INIS)

    Nickell, R.E.

    1980-01-01

    The Serata model is the best operational model available today because it incorporates: (1) a yield function to demarcate between viscoelastic and viscoplastic behavior of rock salt; (2) a pressure and temperature dependence for yield stresses; and (3) a standard linear solid, which can be readily extended into the non-linear regime, to represent creep behavior. Its only deficiencies appear to be the lack of secondary creep behavior (a free dashpot) and some unsettling arbitrariness about the Poisson's ratio (ν → 0.5) argument for viscoplasticity. The Sandia/WIPP model will have good primary and secondary creep capability, but lacks the viscoplastic behavior. In some cases, estimated inelastic strains may be underpredicted. If a creep acceleration mechanism associated with brine inclusions is observed, this model may require extensive revision. Most of the other models available (SAI, RE-SPEC, etc.) are only useful for short-term calculations, because they employ temporal power law (t/sup n/) primary creep representations. These models are unsatisfactory because they cannot represent dual mechanisms with differing characteristic times. An approach based upon combined creep and plasticity is recommended in order to remove the remaining deficiency in the Serata model. DOE/Sandia/WIPP should be encouraged to move aggressively in this regard

  11. Research into basic rocks types

    International Nuclear Information System (INIS)

    1993-06-01

    Teollisuuden Voima Oy (TVO) has carried out research into basic rock types in Finland. The research programme has been implemented in parallel with the preliminary site investigations for radioactive waste disposal in 1991-1993. The program contained two main objectives: firstly, to study the properties of the basic rock types and compare those with the other rock types under the investigation; secondly, to carry out an inventory of rock formations consisting of basic rock types and suitable in question for final disposal. A study of environmental factors important to know regarding the final disposal was made of formations identified. In total 159 formations exceeding the size of 4 km 2 were identified in the inventory. Of these formations 97 were intrusive igneous rock types and 62 originally extrusive volcanic rock types. Deposits consisting of ore minerals, industrial minerals or building stones related to these formations were studied. Environmental factors like natural resources, protected areas or potential for restrictions in land use were also studied

  12. Up-regulation of Rho/ROCK signaling in sarcoma cells drives invasion and increased generation of protrusive forces

    Czech Academy of Sciences Publication Activity Database

    Rosel, D.; Brabek, J.; Tolde, O.; Mierke, C.T.; Zitterbart, D.P.; Raupach, C.; Bicanova, K.; Kollmannsberger, P.; Pánková, D.; Veselý, Pavel; Folk, P.; Fabry, B.

    2008-01-01

    Roč. 6, č. 9 (2008), s. 1410-1420 ISSN 1541-7786 Institutional research plan: CEZ:AV0Z50520514 Keywords : Rho kinase ROCK * traction force microscopy * ameboid invasion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.533, year: 2008

  13. Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa Histone Deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

    Energy Technology Data Exchange (ETDEWEB)

    Compagnucci, Claudia; Barresi, Sabina [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Petrini, Stefania [Research Laboratories, Confocal Microscopy Core Facility, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Zanni, Ginevra, E-mail: ginevra.zanni@opbg.net [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy)

    2015-04-03

    Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin–myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify a new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK. - Highlights: • ROCK regulates nucleocytoplasmic shuttling of HDAC7 via phosphorylation of MYPT1. • Nuclear export of HDAC7 and upregulation of NR4A1 occurs with low ROCK activity. • High levels of ROCK activity due to OPHN1 loss of function downregulate NR4A1.

  14. Modeling the Rock Glacier Cycle

    Science.gov (United States)

    Anderson, R. S.; Anderson, L. S.

    2016-12-01

    Rock glaciers are common in many mountain ranges in which the ELA lies above the peaks. They represent some of the most identifiable components of today's cryosphere in these settings. Their oversteepened snouts pose often-overlooked hazards to travel in alpine terrain. Rock glaciers are supported by avalanches and by rockfall from steep headwalls. The winter's avalanche cone must be sufficiently thick not to melt entirely in the summer. The spatial distribution of rock glaciers reflects this dependence on avalanche sources; they are most common on lee sides of ridges where wind-blown snow augments the avalanche source. In the absence of rockfall, this would support a short, cirque glacier. Depending on the relationship between rockfall and avalanche patterns, "talus-derived" and "glacier-derived" rock glaciers are possible. Talus-derived: If the spatial distribution of rock delivery is similar to the avalanche pattern, the rock-ice mixture will travel an englacial path that is downward through the short accumulation zone before turning upward in the ablation zone. Advected debris is then delivered to the base of a growing surface debris layer that reduces the ice melt rate. The physics is identical to the debris-covered glacier case. Glacier-derived: If on the other hand rockfall from the headwall rolls beyond the avalanche cone, it is added directly to the ablation zone of the glacier. The avalanche accumulation zone then supports a pure ice core to the rock glacier. We have developed numerical models designed to capture the full range of glacier to debris-covered glacier to rock glacier behavior. The hundreds of meter lengths, tens of meters thicknesses, and meter per year speeds of rock glaciers are well described by the models. The model can capture both "talus-derived" and "glacier-derived" rock glaciers. We explore the dependence of glacier behavior on climate histories. As climate warms, a pure ice debris-covered glacier can transform to a much shorter rock

  15. Multiverso: Rock'n'Astronomy

    Science.gov (United States)

    Caballero, J. A.

    2012-05-01

    In the last few years, there have been several projects involving astronomy and classical music. But have a rock band ever appeared at a science conference or an astronomer at a rock concert? We present a project, Multiverso, in which we mix rock and astronomy, together with poetry and video art (Caballero, 2010). The project started in late 2009 and has already reached tens of thousands people in Spain through the release of an album, several concert-talks, television, radio, newspapers and the internet.

  16. Fault rocks and uranium mineralization

    International Nuclear Information System (INIS)

    Tong Hangshou.

    1991-01-01

    The types of fault rocks, microstructural characteristics of fault tectonite and their relationship with uranium mineralization in the uranium-productive granite area are discussed. According to the synthetic analysis on nature of stress, extent of crack and microstructural characteristics of fault rocks, they can be classified into five groups and sixteen subgroups. The author especially emphasizes the control of cataclasite group and fault breccia group over uranium mineralization in the uranium-productive granite area. It is considered that more effective study should be made on the macrostructure and microstructure of fault rocks. It is of an important practical significance in uranium exploration

  17. Test procedures for salt rock

    International Nuclear Information System (INIS)

    Dusseault, M.B.

    1985-01-01

    Potash mining, salt mining, design of solution caverns in salt rocks, disposal of waste in salt repositories, and the use of granular halite backfill in underground salt rock mines are all mining activities which are practised or contemplated for the near future. Whatever the purpose, the need for high quality design parameters is evident. The authors have been testing salt rocks in the laboratory in a number of configurations for some time. Great care has been given to the quality of sample preparation and test methodology. This paper describes the methods, presents the elements of equipment design, and shows some typical results

  18. Chitin and stress induced protein kinase activation

    DEFF Research Database (Denmark)

    Kenchappa, Chandra Shekar; Azevedo da Silva, Raquel; Bressendorff, Simon

    2017-01-01

    The assays described here are pertinent to protein kinase studies in any plant. They include an immunoblot phosphorylation/activation assay and an in-gel activity assay for MAP kinases (MPKs) using the general protein kinase substrate myelin basic protein. They also include a novel in-gel peptide...... substrate assay for Snf1-related kinase family 2 members (SnRK2s). This kinase family-specific assay overcomes some limitations of in-gel assays and permits the identification of different types of kinase activities in total protein extracts....

  19. Fluid and rock interaction in permeable volcanic rock

    International Nuclear Information System (INIS)

    Lindley, J.I.

    1985-01-01

    Four types of interrelated changes -geochemical, mineralogic, isotopic, and physical - occur in Oligocene volcanic units of the Mogollon-Datil volcanic field, New Mexico. These changes resulted from the operation of a geothermal system that, through fluid-rock interaction, affected 5 rhyolite ash-flow tuffs and an intercalated basaltic andesite lava flow causing a potassium metasomatism type of alteration. (1) Previous studies have shown enrichment of rocks in K 2 O as much as 130% of their original values at the expense of Na 2 O and CaO with an accompanying increase in Rb and decreases in MgO and Sr. (2) X-ray diffraction results of this study show that phenocrystic plagioclase and groundmass feldspar have been replaced with pure potassium feldspar and quartz in altered rock. Phenocrystic potassium feldspar, biotite, and quartz are unaffected. Pyroxene in basaltic andesite is replaced by iron oxide. (3) delta 18 O increases for rhyolitic units from values of 8-10 permil, typical of unaltered rock, to 13-15 permil, typical of altered rock. Basaltic andesite, however, shows opposite behavior with a delta 18 of 9 permil in unaltered rock and 6 permit in altered. (4) Alteration results in a density decrease. SEM revealed that replacement of plagioclase by fine-grained quartz and potassium feldspar is not a volume for volume replacement. Secondary porosity is created in the volcanics by the chaotic arrangement of secondary crystals

  20. Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II

    Directory of Open Access Journals (Sweden)

    Drescher Uwe

    2010-06-01

    Full Text Available Abstract Background In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A. It is unknown to what extent these factors contribute to floor plate-derived chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear. Results In this study, we have used a combination of in vitro and in vivo approaches to identify the components of floor plate chemorepulsion and their downstream signalling pathways. Using in vitro motor axon deflection assays, we demonstrate that Slits and Netrin-1, but not Sema3A, contribute to floor plate repulsion. We also find that the axon pathways of dorsally projecting branchiomotor neurons are disrupted in Netrin-1 mutant mice and in chick embryos expressing dominant-negative Unc5a receptors, indicating an in vivo role for Netrin-1. We further demonstrate that Slit and Netrin-1 signalling are mediated by Rho-kinase (ROCK and myosin light chain kinase (MLCK, which regulate myosin II activity, controlling actin retrograde flow in the growth cone. We show that MLCK, ROCK and myosin II are required for Slit and Netrin-1-mediated growth cone collapse of cranial motor axons. Inhibition of these molecules in explant cultures, or genetic manipulation of RhoA or myosin II function in vivo causes characteristic cranial motor axon pathfinding errors, including the inability to exit the midline, and loss of turning towards exit points. Conclusions Our findings suggest that both Slits and Netrin-1 contribute to floor plate-derived chemorepulsion of cranial motor axons. They further indicate that RhoA/ROCK, MLCK and myosin II are components of Slit and Netrin-1 signalling pathways, and suggest that these pathways are of key importance in cranial motor axon navigation.

  1. The Rho-GTPase effector ROCK regulates meiotic maturation of the bovine oocyte via myosin light chain phosphorylation and cofilin phosphorylation.

    Science.gov (United States)

    Lee, So-Rim; Xu, Yong-Nan; Jo, Yu-Jin; Namgoong, Suk; Kim, Nam-Hyung

    2015-11-01

    Oocyte meiosis involves a unique asymmetric division involving spindle movement from the central cytoplasm to the cortex, followed by polar body extrusion. ROCK is a Rho-GTPase effector involved in various cellular functions in somatic cells as well as oocyte meiosis. ROCK was previously shown to promote actin organization by phosphorylating several downstream targets, including LIM domain kinase (LIMK), phosphorylated cofilin (p-cofilin), and myosin light chain (MLC). In this study, we investigated the roles of ROCK and MLC during bovine oocyte meiosis. We found that ROCK was localized around the nucleus at the oocyte's germinal-vesicle (GV) stage, but spreads to the rest of the cytoplasm in later developmental stages. On the other hand, phosphorylated MLC (p-MLC) localized at the cortex, and its abundance decreased by the metaphase-II stage. Disrupting ROCK activity, via RNAi or the chemical inhibitor Y-27632, blocked both cell cycle progression and polar body extrusion. ROCK inhibition also resulted in decreased cortical actin, p-cofilin, and p-MLC levels. Similar to the phenotype associated with inhibition of ROCK activity, inhibition of MLC kinase by the chemical inhibitor ML-7 caused defects in polar body extrusion. Collectively, our results suggest that the ROCK/MLC/actomyosin as well as ROCK/LIMK/cofilin pathways regulate meiotic spindle migration and cytokinesis during bovine oocyte maturation. © 2015 Wiley Periodicals, Inc.

  2. Beach rock from Goa Coast

    Digital Repository Service at National Institute of Oceanography (India)

    Setty, M.G.A.P.; Wagle, B.G.

    constituents of beach rock found along Goa coast is dealt with in detail. While discussing the various views on its origin, it is emphasized that the process of cementation is chiefly controlled by ground water evaporation, inorganic precipitation and optimum...

  3. The Chronology of Rock Art

    Indian Academy of Sciences (India)

    Such phases are tentatively ascribed to different archaeological cultures on the basis of the contextual availability, stylistic similarities and so on. Ethnographic analogies are also attempted in the dating of rock art .

  4. Chemical methods of rock analysis

    National Research Council Canada - National Science Library

    Jeffery, P. G; Hutchison, D

    1981-01-01

    A practical guide to the methods in general use for the complete analysis of silicate rock material and for the determination of all those elements present in major, minor or trace amounts in silicate...

  5. Heat production in granitic rocks

    DEFF Research Database (Denmark)

    Artemieva, Irina; Thybo, Hans; Jakobsen, Kiki

    2017-01-01

    Granitic rocks play special role in the dynamics and evolution of the Earth and its thermal regime. First, their compositional variability, reflected in the distribution of concentrations of radiogenic elements, provides constraints on global differentiation processes and large scale planetary...... evolution, where emplacement of granites is considered a particularly important process for the formation of continental crust. Second, heat production by radioactive decay is among the main heat sources in the Earth. Therefore knowledge of heat production in granitic rocks is pivotal for thermal modelling...... of the continental lithosphere, given that most radiogenic elements are concentrated in granitic rocks of the upper continental crust whereas heat production in rocks of the lower crust and lithospheric mantle is negligible. We present and analyze a new global database GRANITE2017 (with about 500 entries...

  6. Defending dreamer’s rock

    OpenAIRE

    Beck, Günter U.

    2007-01-01

    Defending dreamer’s rock : Geschichte, Geschichtsbewusstsein und Geschichtskultur im Native drama der USA und Kanadas. - Trier : WVT Wiss. Verl. Trier, 2007. - 445 S. - (CDE - Studies ; 14). - Zugl.: Augsburg, Univ., Diss., 2006

  7. Predicting rock bursts in mines

    Science.gov (United States)

    Spall, H.

    1979-01-01

    In terms of lives lost, rock bursts in underground mines can be as hazardous as earthquakes on the surface. So it is not surprising that fo the last 40 years the U.S Bureau of Mines has been using seismic methods for detecting areas in underground mines where there is a high differential stress which could lead to structural instability of the rock mass being excavated.

  8. Thermally induced rock stress increment and rock reinforcement response

    International Nuclear Information System (INIS)

    Hakala, M.; Stroem, J.; Nujiten, G.; Uotinen, L.; Siren, T.; Suikkanen, J.

    2014-07-01

    This report describes a detailed study of the effect of thermal heating by the spent nuclear fuel containers on the in situ rock stress, any potential rock failure, and associated rock reinforcement strategies for the Olkiluoto underground repository. The modelling approach and input data are presented together repository layout diagrams. The numerical codes used to establish the effects of heating on the in situ stress field are outlined, together with the rock mass parameters, in situ stress values, radiogenic temperatures and reinforcement structures. This is followed by a study of the temperature and stress evolution during the repository's operational period and the effect of the heating on the reinforcement structures. It is found that, during excavation, the maximum principal stress is concentrated at the transition areas where the profile changes and that, due to the heating from the deposition of spent nuclear fuel, the maximum principal stress rises significantly in the tunnel arch area of NW/SW oriented central tunnels. However, it is predicted that the rock's crack damage (CD, short term strength) value of 99 MPa will not be exceeded anywhere within the model. Loads onto the reinforcement structures will come from damaged and loosened rock which is assumed in the modelling as a free rock wedge - but this is very much a worst case scenario because there is no guarantee that rock cracking would form a free rock block. The structural capacity of the reinforcement structures is described and it is predicted that the current quantity of the rock reinforcement is strong enough to provide a stable tunnel opening during the peak of the long term stress state, with damage predicted on the sprayed concrete liner. However, the long term stability and safety can be improved through the implementation of the principles of the Observational Method. The effect of ventilation is also considered and an additional study of the radiogenic heating effect on the brittle

  9. Thermally induced rock stress increment and rock reinforcement response

    Energy Technology Data Exchange (ETDEWEB)

    Hakala, M. [KMS Hakala Oy, Nokia (Finland); Stroem, J.; Nujiten, G.; Uotinen, L. [Rockplan, Helsinki (Finland); Siren, T.; Suikkanen, J.

    2014-07-15

    This report describes a detailed study of the effect of thermal heating by the spent nuclear fuel containers on the in situ rock stress, any potential rock failure, and associated rock reinforcement strategies for the Olkiluoto underground repository. The modelling approach and input data are presented together repository layout diagrams. The numerical codes used to establish the effects of heating on the in situ stress field are outlined, together with the rock mass parameters, in situ stress values, radiogenic temperatures and reinforcement structures. This is followed by a study of the temperature and stress evolution during the repository's operational period and the effect of the heating on the reinforcement structures. It is found that, during excavation, the maximum principal stress is concentrated at the transition areas where the profile changes and that, due to the heating from the deposition of spent nuclear fuel, the maximum principal stress rises significantly in the tunnel arch area of NW/SW oriented central tunnels. However, it is predicted that the rock's crack damage (CD, short term strength) value of 99 MPa will not be exceeded anywhere within the model. Loads onto the reinforcement structures will come from damaged and loosened rock which is assumed in the modelling as a free rock wedge - but this is very much a worst case scenario because there is no guarantee that rock cracking would form a free rock block. The structural capacity of the reinforcement structures is described and it is predicted that the current quantity of the rock reinforcement is strong enough to provide a stable tunnel opening during the peak of the long term stress state, with damage predicted on the sprayed concrete liner. However, the long term stability and safety can be improved through the implementation of the principles of the Observational Method. The effect of ventilation is also considered and an additional study of the radiogenic heating effect on the

  10. Non-Viral Deoxyribonucleoside Kinases

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Munch-Petersen, Birgitte; Knecht, Wolfgang

    2015-01-01

    Deoxyribonucleoside kinases (dNKs) phosphorylate deoxyribonucleosides to their corresponding monophosphate compounds. dNks also phosphorylate deoxyribonucleoside analogues that are used in the treatment of cancer or viral infections. The study of the mammalian dNKs has therefore always been of gr...

  11. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure...

  12. Evaluation of Rock Bolt Support for Polish Hard Rock Mines

    Science.gov (United States)

    Skrzypkowski, Krzysztof

    2018-03-01

    The article presents different types of rock bolt support used in Polish ore mining. Individual point resin and expansion rock bolt support were characterized. The roof classes for zinc and lead and copper ore mines were presented. Furthermore, in the article laboratory tests of point resin rock bolt support in a geometric scale of 1:1 with minimal fixing length of 0.6 m were made. Static testing of point resin rock bolt support were carried out on a laboratory test facility of Department of Underground Mining which simulate mine conditions for Polish ore and hard coal mining. Laboratory tests of point resin bolts were carried out, especially for the ZGH Bolesław, zinc and lead "Olkusz - Pomorzany" mine. The primary aim of the research was to check whether at the anchoring point length of 0.6 m by means of one and a half resin cartridge, the type bolt "Olkusz - 20A" is able to overcome the load.The second purpose of the study was to obtain load - displacement characteristic with determination of the elastic and plastic range of the bolt. For the best simulation of mine conditions the station steel cylinders with an external diameter of 0.1 m and a length of 0.6 m with a core of rock from the roof of the underground excavations were used.

  13. Seismic response of rock joints and jointed rock mass

    International Nuclear Information System (INIS)

    Ghosh, A.; Hsiung, S.M.; Chowdhury, A.H.

    1996-06-01

    Long-term stability of emplacement drifts and potential near-field fluid flow resulting from coupled effects are among the concerns for safe disposal of high-level nuclear waste (HLW). A number of factors can induce drift instability or change the near-field flow patterns. Repetitive seismic loads from earthquakes and thermal loads generated by the decay of emplaced waste are two significant factors. One of two key technical uncertainties (KTU) that can potentially pose a high risk of noncompliance with the performance objectives of 10 CFR Part 60 is the prediction of thermal-mechanical (including repetitive seismic load) effects on stability of emplacement drifts and the engineered barrier system. The second KTU of concern is the prediction of thermal-mechanical-hydrological (including repetitive seismic load) effects on the host rock surrounding the engineered barrier system. The Rock Mechanics research project being conducted at the Center for Nuclear Waste Regulatory Analyses (CNWRA) is intended to address certain specific technical issues associated with these two KTUs. This research project has two major components: (i) seismic response of rock joints and a jointed rock mass and (ii) coupled thermal-mechanical-hydrological (TMH) response of a jointed rock mass surrounding the engineered barrier system (EBS). This final report summarizes the research activities concerned with the repetitive seismic load aspect of both these KTUs

  14. 30 CFR 57.3461 - Rock bursts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rock bursts. 57.3461 Section 57.3461 Mineral...-Underground Only § 57.3461 Rock bursts. (a) Operators of mines which have experienced a rock burst shall— (1) Within twenty four hours report to the nearest MSHA office each rock burst which: (i) Causes persons to...

  15. Autoregulation of kinase dephosphorylation by ATP binding in AGC protein kinases.

    Science.gov (United States)

    Chan, Tung O; Pascal, John M; Armen, Roger S; Rodeck, Ulrich

    2012-02-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non- ATP-competitive kinase inhibitors that discriminate within and between protein kinase families.

  16. Autoregulation of kinase dephosphorylation by ATP binding to AGC protein kinases

    Science.gov (United States)

    Pascal, John M; Armen, Roger S

    2012-01-01

    AGC kinases, including the three Akt (protein kinase B) isoforms, protein kinase A (PKA) and all protein kinase C (PKC) isoforms, require activation loop phosphorylation (threonine 308 in Akt1) as well as phosphorylation of a C-terminal residue (serine 473 in Akt1) for catalytic activity and phosphorylation of downstream targets. Conversely, phosphatases reverse these phosphorylations. Virtually all cellular processes are affected by AGC kinases, a circumstance that has led to intense scrutiny of the molecular mechanisms that regulate phosphorylation of these kinases. Here, we review a new layer of control of phosphorylation in Akt, PKA and PKC pointing to ATP binding pocket occupancy as a means to decelerate dephosphorylation of these and, potentially, other kinases. This additional level of kinase regulation opens the door to search for new functional motifs for the rational design of non-ATP-competitive kinase inhibitors that discriminate within and between protein kinase families. PMID:22262182

  17. A collapsin response mediator protein 2 isoform controls myosin II-mediated cell migration and matrix assembly by trapping ROCK II

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Morgan-Fisher, Marie; Wait, Robin

    2012-01-01

    Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among...... nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two......-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions...

  18. Current status of crushed rock and whole rock column studies

    International Nuclear Information System (INIS)

    Vine, E.N.; Daniels, W.R.; Rundberg, R.S.; Thompson, J.L.

    1980-01-01

    Measurements on a large number of crushed rock columns of tuff, granite, and argillite are discussed. The isotopes 85 Sr, 137 Cs, 133 Ba, 141 Ce, 152 Eu, /sup 95m/Tc, and 233 U were used. Flow rates were varied from approx. 30 to approx. 30000 m/y. Other parameters studied include isotope concentration and atmosphere. The sorption ratios calculated were compared with batch sorption ratios on the same samples. Methods of studying the movement of radionuclides through whole rock cores are described. The problems associated with sealing the cores to prevent leaking along the exterior surface and one possible solution are discussed. The strontium sorption ratio obtained by elution of one solid tuff core is compared with the batch and crushed rock column sorption ratios

  19. Src kinase regulation by phosphorylation and dephosphorylation

    International Nuclear Information System (INIS)

    Roskoski, Robert

    2005-01-01

    Src and Src-family protein-tyrosine kinases are regulatory proteins that play key roles in cell differentiation, motility, proliferation, and survival. The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation, and an inhibiting phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase (Csk) and Csk homologous kinase. Dephosphorylation of phosphotyrosine 527 increases Src kinase activity. Candidate phosphotyrosine 527 phosphatases include cytoplasmic PTP1B, Shp1 and Shp2, and transmembrane enzymes include CD45, PTPα, PTPε, and PTPλ. Dephosphorylation of phosphotyrosine 416 decreases Src kinase activity. Thus far PTP-BL, the mouse homologue of human PTP-BAS, has been shown to dephosphorylate phosphotyrosine 416 in a regulatory fashion. The platelet-derived growth factor receptor protein-tyrosine kinase mediates the phosphorylation of Src Tyr138; this phosphorylation has no direct effect on Src kinase activity. The platelet-derived growth factor receptor and the ErbB2/HER2 growth factor receptor protein-tyrosine kinases mediate the phosphorylation of Src Tyr213 and activation of Src kinase activity. Src kinase is also a substrate for protein-serine/threonine kinases including protein kinase C (Ser12), protein kinase A (Ser17), and CDK1/cdc2 (Thr34, Thr46, and Ser72). Of the three protein-serine/threonine kinases, only phosphorylation by CDK1/cdc2 has been demonstrated to increase Src kinase activity. Although considerable information on the phosphoprotein phosphatases that catalyze the hydrolysis of Src phosphotyrosine 527 is at hand, the nature of the phosphatases that mediate the hydrolysis of phosphotyrosine 138 and 213, and phosphoserine and phosphothreonine residues has not been determined

  20. Rock Pore Structure as Main Reason of Rock Deterioration

    Directory of Open Access Journals (Sweden)

    Ondrášik Martin

    2014-03-01

    Full Text Available Crashed or dimensional rocks have been used as natural construction material, decoration stone or as material for artistic sculptures. Especially old historical towns not only in Slovakia have had experiences with use of stones for construction purposes for centuries. The whole buildings were made from dimensional stone, like sandstone, limestone or rhyolite. Pavements were made especially from basalt, andesite, rhyolite or granite. Also the most common modern construction material - concrete includes large amounts of crashed rock, especially limestone, dolostone and andesite.

  1. Fracture characteristics in Japanese rock

    International Nuclear Information System (INIS)

    Ijiri, Yuji; Sawada, Atsushi; Akahori, Kuniaki

    1999-11-01

    It is crucial for the performance assessment of geosphere to evaluate the characteristics of fractures that can be dominant radionuclide migration pathways from a repository to biosphere. This report summarizes the characteristics of fractures obtained from broad literature surveys and the fields surveys at the Kamaishi mine in northern Japan and at outcrops and galleries throughout the country. The characteristics of fractures described in this report are fracture orientation, fracture shape, fracture frequency, fracture distribution in space, transmissivity of fracture, fracture aperture, fracture fillings, alteration halo along fracture, flow-wetted surface area in fracture, and the correlation among these characteristics. Since granitic rock is considered the archetype fractured media, a large amount of fracture data is available in literature. In addition, granitic rock has been treated as a potential host rock in many overseas programs, and has JNC performed a number of field observations and experiments in granodiorite at the Kamaishi mine. Therefore, the characteristics of fractures in granitic rock are qualitatively and quantitatively clarified to some extent in this report, while the characteristics of fractures in another rock types are not clarified. (author)

  2. Hot dry rock heat mining

    International Nuclear Information System (INIS)

    Duchane, D.V.

    1992-01-01

    Geothermal energy utilizing fluids from natural sources is currently exploited on a commercial scale at sites around the world. A much greater geothermal resource exists, however, in the form of hot rock at depth which is essentially dry. This hot dry rock (HDR) resource is found almost everywhere, but the depth at which usefully high temperatures are reached varies from place to place. The technology to mine the thermal energy from HDR has been under development for a number of years. Using techniques adapted from the petroleum industry, water is pumped at high pressure down an injection well to a region of usefully hot rock. The pressure forces open natural joints to form a reservoir consisting of a small amount of water dispensed in a large volume of hot rock. This reservoir is tapped by second well located at some distance from the first, and the heated water is brought to the surface where its thermal energy is extracted. The same water is then recirculated to mine more heat. Economic studies have indicated that it may be possible to produce electricity at competitive prices today in regions where hot rock is found relatively close to the surface

  3. Signaling network of the Btk family kinases.

    Science.gov (United States)

    Qiu, Y; Kung, H J

    2000-11-20

    The Btk family kinases represent new members of non-receptor tyrosine kinases, which include Btk/Atk, Itk/Emt/Tsk, Bmx/Etk, and Tec. They are characterized by having four structural modules: PH (pleckstrin homology) domain, SH3 (Src homology 3) domain, SH2 (Src homology 2) domain and kinase (Src homology 1) domain. Increasing evidence suggests that, like Src-family kinases, Btk family kinases play central but diverse modulatory roles in various cellular processes. They participate in signal transduction in response to virtually all types of extracellular stimuli which are transmitted by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen-receptors and integrins. They are regulated by many non-receptor tyrosine kinases such as Src, Jak, Syk and FAK family kinases. In turn, they regulate many of major signaling pathways including those of PI3K, PLCgamma and PKC. Both genetic and biochemical approaches have been used to dissect the signaling pathways and elucidate their roles in growth, differentiation and apoptosis. An emerging new role of this family of kinases is cytoskeletal reorganization and cell motility. The physiological importance of these kinases was amply demonstrated by their link to the development of immunodeficiency diseases, due to germ-line mutations. The present article attempts to review the structure and functions of Btk family kinases by summarizing our current knowledge on the interacting partners associated with the different modules of the kinases and the diverse signaling pathways in which they are involved.

  4. Receptor-interacting protein (RIP) kinase family

    Science.gov (United States)

    Zhang, Duanwu; Lin, Juan; Han, Jiahuai

    2010-01-01

    Receptor-interacting protein (RIP) kinases are a group of threonine/serine protein kinases with a relatively conserved kinase domain but distinct non-kinase regions. A number of different domain structures, such as death and caspase activation and recruitment domain (CARD) domains, were found in different RIP family members, and these domains should be keys in determining the specific function of each RIP kinase. It is known that RIP kinases participate in different biological processes, including those in innate immunity, but their downstream substrates are largely unknown. This review will give an overview of the structures and functions of RIP family members, and an update of recent progress in RIP kinase research. PMID:20383176

  5. Thermal expansion of granite rocks

    International Nuclear Information System (INIS)

    Stephansson, O.

    1978-04-01

    The thermal expansion of rocks is strongly controlled by the thermal expansion of the minerals. The theoretical thermal expansion of the Stripa Granite is gound to be 21 . 10 -6 [deg C] -1 at 25 deg C and 38 . 10 -6 [deg C] -1 at 400 deg C. The difference in expansion for the rock forming minerals causes micro cracking at heating. The expansion due to micro cracks is found to be of the same order as the mineral expansion. Most of the micro cracks will close at pressures of the order of 10 - 20 MPa. The thermal expansion of a rock mass including the effect of joints is determined in the pilot heater test in the Stripa Mine

  6. Oncoprotein protein kinase antibody kit

    Science.gov (United States)

    Karin, Michael [San Diego, CA; Hibi, Masahiko [San Diego, CA; Lin, Anning [La Jolla, CA

    2008-12-23

    An isolated polypeptide (JNK) characterized by having a molecular weight of 46 kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

  7. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.

    2006-01-01

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The....... The TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  8. Uranium endowments in phosphate rock

    International Nuclear Information System (INIS)

    Ulrich, Andrea E.; Schnug, Ewald; Prasser, Horst-Michael; Frossard, Emmanuel

    2014-01-01

    This study seeks to identify and specify the components that make up the prospects of U recovery from phosphate rock. A systems approach is taken. The assessment includes i) reviewing past recovery experience and lessons learned; ii) identifying factors that determine recovery; and iii) establishing a contemporary evaluation of U endowments in phosphate rock reserves, as well as the available and recoverable amounts from phosphate rock and phosphoric acid production. We find that in the past, recovery did not fulfill its potential and that the breakup of the Soviet Union worsened then-favorable recovery market conditions in the 1990s. We find that an estimated 5.7 million tU may be recoverable from phosphate rock reserves. In 2010, the recoverable tU from phosphate rock and phosphoric acid production may have been 15,000 tU and 11,000 tU, respectively. This could have filled the world U supply-demand gap for nuclear energy production. The results suggest that the U.S., Morocco, Tunisia, and Russia would be particularly well-suited to recover U, taking infrastructural considerations into account. We demonstrate future research needs, as well as sustainability orientations. We conclude that in order to promote investment and production, it seems necessary to establish long-term contracts at guaranteed prices, ensuring profitability for phosphoric acid producers. - Highlights: • We identify components that underlie the recovery of uranium from phosphate rock. • We estimate that 11,000 tU may have been recoverable from phosphoric acid in 2010. • Recovery is a resource conservation and environmental pollution control strategy. • To ensure investment in recovery technology, profitability needs to be secured

  9. Uranium deposits in granitic rocks

    International Nuclear Information System (INIS)

    Nishimori, R.K.; Ragland, P.C.; Rogers, J.J.W.; Greenberg, J.K.

    1977-01-01

    This report is a review of published data bearing on the geology and origin of uranium deposits in granitic, pegmatitic and migmatitic rocks with the aim of assisting in the development of predictive criteria for the search for similar deposits in the U.S. Efforts were concentrated on the so-called ''porphyry'' uranium deposits. Two types of uranium deposits are primarily considered: deposits in pegmatites and alaskites in gneiss terrains, and disseminations of uranium in high-level granites. In Chapter 1 of this report, the general data on the distribution of uranium in igneous and metamorphic rocks are reviewed. Chapter 2 contains some comments on the classification of uranium deposits associated with igneous rocks and a summary of the main features of the geology of uranium deposits in granites. General concepts of the behavior of uranium in granites during crustal evolution are reviewed in Chapter 3. Also included is a discussion of the relationship of uranium mineralization in granites to the general evolution of mobile belts, plus the influence of magmatic and post-magmatic processes on the distribution of uranium in igneous rocks and related ore deposits. Chapter 4 relates the results of experimental studies on the crystallization of granites to some of the geologic features of uranium deposits in pegmatites and alaskites in high-grade metamorphic terrains. Potential or favorable areas for igneous uranium deposits in the U.S.A. are delineated in Chapter 5. Data on the geology of specific uranium deposits in granitic rocks are contained in Appendix 1. A compilation of igneous rock formations containing greater than 10 ppM uranium is included in Appendix 2. Appendix 3 is a report on the results of a visit to the Roessing area. Appendix 4 is a report on a field excursion to eastern Canada

  10. Uranium endowments in phosphate rock

    Energy Technology Data Exchange (ETDEWEB)

    Ulrich, Andrea E., E-mail: andrea.ulrich@env.ethz.ch [Institute for Environmental Decisions (IED), Natural and Social Science Interface, ETH Zurich Universitässtrasse 22, 8092 Zurich (Switzerland); Institute for Agricultural Sciences, Plant Nutrition, ETH Zurich, Eschikon 33, 8315 Lindau (Switzerland); Schnug, Ewald, E-mail: e.schnug@tu-braunschweig.de [Department of Life Sciences, Technical University of Braunschweig, Pockelsstraße 14, D-38106 Braunschweig (Germany); Prasser, Horst-Michael, E-mail: prasser@lke.mavt.ethz.ch [Institute of Energy Technology, Laboratory of Nuclear Energy Systems, ETH Zurich, Sonneggstrasse 3, 8092 Zurich (Switzerland); Frossard, Emmanuel, E-mail: emmanuel.frossard@usys.ethz.ch [Institute for Agricultural Sciences, Plant Nutrition, ETH Zurich, Eschikon 33, 8315 Lindau (Switzerland)

    2014-04-01

    This study seeks to identify and specify the components that make up the prospects of U recovery from phosphate rock. A systems approach is taken. The assessment includes i) reviewing past recovery experience and lessons learned; ii) identifying factors that determine recovery; and iii) establishing a contemporary evaluation of U endowments in phosphate rock reserves, as well as the available and recoverable amounts from phosphate rock and phosphoric acid production. We find that in the past, recovery did not fulfill its potential and that the breakup of the Soviet Union worsened then-favorable recovery market conditions in the 1990s. We find that an estimated 5.7 million tU may be recoverable from phosphate rock reserves. In 2010, the recoverable tU from phosphate rock and phosphoric acid production may have been 15,000 tU and 11,000 tU, respectively. This could have filled the world U supply-demand gap for nuclear energy production. The results suggest that the U.S., Morocco, Tunisia, and Russia would be particularly well-suited to recover U, taking infrastructural considerations into account. We demonstrate future research needs, as well as sustainability orientations. We conclude that in order to promote investment and production, it seems necessary to establish long-term contracts at guaranteed prices, ensuring profitability for phosphoric acid producers. - Highlights: • We identify components that underlie the recovery of uranium from phosphate rock. • We estimate that 11,000 tU may have been recoverable from phosphoric acid in 2010. • Recovery is a resource conservation and environmental pollution control strategy. • To ensure investment in recovery technology, profitability needs to be secured.

  11. Evaluation of Rock Joint Coefficients

    Science.gov (United States)

    Audy, Ondřej; Ficker, Tomáš

    2017-10-01

    A computer method for evaluation of rock joint coefficients is described and several applications are presented. The method is based on two absolute numerical indicators that are formed by means of the Fourier replicas of rock joint profiles. The first indicator quantifies the vertical depth of profiles and the second indicator classifies wavy character of profiles. The absolute indicators have replaced the formerly used relative indicators that showed some artificial behavior in some cases. This contribution is focused on practical computations testing the functionality of the newly introduced indicators.

  12. Ultrasonically assisted drilling of rocks

    Science.gov (United States)

    Mikhailova, N. V.; Onawumi, P. Y.; Roy, A.; Silberschmidt, V. V.

    2018-05-01

    Conventional drilling of rocks can generate significant damage in the drilled material; a material layer is often split off a back surface of a sample during drilling, negatively affecting its strength. To improve finish quality, ultrasonically assisted drilling (UAD) was employed in two rocks - sandstone and marble. Damage areas in both materials were reduced in UAD when compared to conventional drilling. Reductions in a thrust force and a torque reduction were observed only for UAD in marble; ultrasonic assistance in sandstone drilling did not result in improvements in this regard.

  13. Rock mechanics studies for SMES

    International Nuclear Information System (INIS)

    Haimson, B.C.

    1981-01-01

    Superconducting magnetic energy storage (SMES) systems capable of storing thousands of MWh develop tremendous magnetically induced forces when charged. To prevent rutpure of the magnets these forces must be confined. Bedrock offers a practical and relatively inexpensive magnet containment structure. This paper examines the need for rock mechanics research in connection with the construction and use of SMES rock caverns; the unique problems related to housing superconducting magnets in bedrock; site investigations of granite, quartzite and dolomite deposits in Wisconsin; and cavern design requirements to assure cavern stability and limited deformation under the expected mechanical leads. Recommendations are made for siting SMES caverns

  14. Source rock potential of middle cretaceous rocks in Southwestern Montana

    Science.gov (United States)

    Dyman, T.S.; Palacas, J.G.; Tysdal, R.G.; Perry, W.J.; Pawlewicz, M.J.

    1996-01-01

    The middle Cretaceous in southwestern Montana is composed of a marine and nonmarine succession of predominantly clastic rocks that were deposited along the western margin of the Western Interior Seaway. In places, middle Cretaceous rocks contain appreciable total organic carbon (TOC), such as 5.59% for the Mowry Shale and 8.11% for the Frontier Formation in the Madison Range. Most samples, however, exhibit less than 1.0% TOC. The genetic or hydrocarbon potential (S1+S2) of all the samples analyzed, except one, yield less than 1 mg HC/g rock, strongly indicating poor potential for generating commercial amounts of hydrocarbons. Out of 51 samples analyzed, only one (a Thermopolis Shale sample from the Snowcrest Range) showed a moderate petroleum potential of 3.1 mg HC/g rock. Most of the middle Cretaceous samples are thermally immature to marginally mature, with vitrinite reflectance ranging from about 0.4 to 0.6% Ro. Maturity is high in the Pioneer Mountains, where vitrinite reflectance averages 3.4% Ro, and at Big Sky Montana, where vitrinite reflectance averages 2.5% Ro. At both localities, high Ro values are due to local heat sources, such as the Pioneer batholith in the Pioneer Mountains.

  15. A Collapsin Response Mediator Protein 2 Isoform Controls Myosin II-Mediated Cell Migration and Matrix Assembly by Trapping ROCK II

    Science.gov (United States)

    Morgan-Fisher, Marie; Wait, Robin; Couchman, John R.; Wewer, Ulla M.

    2012-01-01

    Collapsin response mediator protein 2 (CRMP-2) is known as a regulator of neuronal polarity and differentiation through microtubule assembly and trafficking. Here, we show that CRMP-2 is ubiquitously expressed and a splice variant (CRMP-2L), which is expressed mainly in epithelial cells among nonneuronal cells, regulates myosin II-mediated cellular functions, including cell migration. While the CRMP-2 short form (CRMP-2S) is recognized as a substrate of the Rho-GTP downstream kinase ROCK in neuronal cells, a CRMP-2 complex containing 2L not only bound the catalytic domain of ROCK II through two binding domains but also trapped and inhibited the kinase. CRMP-2L protein levels profoundly affected haptotactic migration and the actin-myosin cytoskeleton of carcinoma cells as well as nontransformed epithelial cell migration in a ROCK activity-dependent manner. Moreover, the ectopic expression of CRMP-2L but not -2S inhibited fibronectin matrix assembly in fibroblasts. Underlying these responses, CRMP-2L regulated the kinase activity of ROCK II but not ROCK I, independent of GTP-RhoA levels. This study provides a new insight into CRMP-2 as a controller of myosin II-mediated cellular functions through the inhibition of ROCK II in nonneuronal cells. PMID:22431514

  16. Soft Rock Yields Clues to Mars' Past

    Science.gov (United States)

    2004-01-01

    [figure removed for brevity, see original site] Figure 1 This image taken by the Mars Exploration Rover Spirit shows the rock outcrop dubbed 'Clovis.' The rock was discovered to be softer than other rocks studied so far at Gusev Crater after the rover easily ground a hole into it with its rock abrasion tool. Spirit's solar panels can be seen in the foreground. This image was taken by the rover's navigation camera on sol 205 (July 31, 2004). Elemental Trio Found in 'Clovis' Figure 1 above shows that the interior of the rock dubbed 'Clovis' contains higher concentrations of sulfur, bromine and chlorine than basaltic, or volcanic, rocks studied so far at Gusev Crater. The data were taken by the Mars Exploration Rover Spirit's alpha particle X-ray spectrometer after the rover dug into Clovis with its rock abrasion tool. The findings might indicate that this rock was chemically altered, and that fluids once flowed through the rock depositing these elements.

  17. Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension.

    Science.gov (United States)

    Su, Hao; Yan, Ji; Xu, Jian; Fan, Xi-Zhen; Sun, Xian-Lin; Chen, Kang-Yu

    2015-08-01

    Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho-kinase (ROCK) pathway plays a central role in the pathologic progression of PH and thus the Rho kinase, an essential effector of the ROCK pathway, is considered as a potential therapeutic target to attenuate PH. In the current study, a synthetic pipeline is used to discover new potent Rho inhibitors from various natural products. In the pipeline, the stepwise high-throughput virtual screening, quantitative structure-activity relationship (QSAR)-based rescoring, and kinase assay were integrated. The screening was performed against a structurally diverse, drug-like natural product library, from which six identified compounds were tested to determine their inhibitory potencies agonist Rho by using a standard kinase assay protocol. With this scheme, we successfully identified two potent Rho inhibitors, namely phloretin and baicalein, with activity values of IC50 = 0.22 and 0.95 μM, respectively. Structural examination suggested that complicated networks of non-bonded interactions such as hydrogen bonding, hydrophobic forces, and van der Waals contacts across the complex interfaces of Rho kinase are formed with the screened compounds.

  18. Review on the prevailing methods for the prediction of potential rock burst / rock spalling in tunnels

    OpenAIRE

    Panthi, Krishna Kanta

    2017-01-01

    Rock burst / rock spalling is among the prevailing stability challenges, which can be met while tunneling through hard rock mass. Especially, this is very relevant for the mountainous country like Norway where hard rock is dominating and many road, railway and hydropower tunnels have to be aligned deep into the mountain with steep valley slope topography. Tunnels passing beneath deep rock cover (overburden), in general, are subjected to high in-situ stresses. If the rock mass is relatively un...

  19. Kinases Involved in Both Autophagy and Mitosis.

    Science.gov (United States)

    Li, Zhiyuan; Zhang, Xin

    2017-08-31

    Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases), Aurora kinases, PLK-1 (polo-like kinase 1), BUB1 (budding uninhibited by benzimidazoles 1), MAPKs (mitogen-activated protein kinases), mTORC1 (mechanistic target of rapamycin complex 1), AMPK (AMP-activated protein kinase), PI3K (phosphoinositide-3 kinase) and protein kinase B (AKT). By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  20. Kinases Involved in Both Autophagy and Mitosis

    Directory of Open Access Journals (Sweden)

    Zhiyuan Li

    2017-08-01

    Full Text Available Both mitosis and autophagy are highly regulated dynamic cellular processes and involve various phosphorylation events catalysed by kinases, which play vital roles in almost all physiological and pathological conditions. Mitosis is a key event during the cell cycle, in which the cell divides into two daughter cells. Autophagy is a process in which the cell digests its own cellular contents. Although autophagy regulation has mainly been studied in asynchronous cells, increasing evidence indicates that autophagy is in fact tightly regulated in mitosis. Here in this review, we will discuss kinases that were originally identified to be involved in only one of either mitosis or autophagy, but were later found to participate in both processes, such as CDKs (cyclin-dependent kinases, Aurora kinases, PLK-1 (polo-like kinase 1, BUB1 (budding uninhibited by benzimidazoles 1, MAPKs (mitogen-activated protein kinases, mTORC1 (mechanistic target of rapamycin complex 1, AMPK (AMP-activated protein kinase, PI3K (phosphoinositide-3 kinase and protein kinase B (AKT. By focusing on kinases involved in both autophagy and mitosis, we will get a more comprehensive understanding about the reciprocal regulation between the two key cellular events, which will also shed light on their related therapeutic investigations.

  1. Simulation of rock deformation behavior

    Directory of Open Access Journals (Sweden)

    Я. И. Рудаев

    2016-12-01

    Full Text Available A task of simulating the deformation behavior of geomaterials under compression with account of over-extreme branch has been addressed. The physical nature of rock properties variability as initially inhomogeneous material is explained by superposition of deformation and structural transformations of evolutionary type within open nonequilibrium systems. Due to this the description of deformation and failure of rock is related to hierarchy of instabilities within the system being far from thermodynamic equilibrium. It is generally recognized, that the energy function of the current stress-strain state is a superposition of potential component and disturbance, which includes the imperfection parameter accounting for defects not only existing in the initial state, but also appearing under load. The equation of state has been obtained by minimizing the energy function by the order parameter. The imperfection parameter is expressed through the strength deterioration, which is viewed as the internal parameter of state. The evolution of strength deterioration has been studied with the help of Fokker – Planck equation, which steady form corresponds to rock statical stressing. Here the diffusion coefficient is assumed to be constant, while the function reflecting internal sliding and loosening of the geomaterials is assumed as an antigradient of elementary integration catastrophe. Thus the equation of state is supplemented with a correlation establishing relationship between parameters of imperfection and strength deterioration. While deformation process is identified with the change of dissipative media, coupled with irreversible structural fluctuations. Theoretical studies are proven with experimental data obtained by subjecting certain rock specimens to compression.

  2. Los abuelos de nuestro rock

    Directory of Open Access Journals (Sweden)

    Jacobo Celnik

    2016-12-01

    Full Text Available Los Yetis. Una bomba atómica a go go. La historia de los abuelos de nuestro rock. Diego Londoño; Pulso & Letra Editores, Instituto para el Desarrollo de Antioquia, Instituto de Cultura y Patrimonio de Antioquia, 2014, 98 págs., fotografías.

  3. Gas migration in argillaceous rock

    International Nuclear Information System (INIS)

    Alonso, E. E.; Olivella, S.

    2007-01-01

    The intrinsic gas permeability of fractured argillaceous rocks depends on the current structure of micro-cracks and fissures of the rock. They are a consequence of the initial state and the subsequent deformations induced by stress and gas pressure changes. Stresses are also coupled with fluid pressures and, therefore, gas flow and mechanical behaviour are intensely coupled. Laboratory experiments, aimed at determining intrinsic permeability, show the relevant effect of volumetric deformations induced by isotropic, as well as deviatoric stress changes. The relevance, in practice, of the flow-mechanical coupling is illustrated by means of some results obtained during the performance of the drift scale test (DST) in fractured tuff in the Yucca Mountain facility. The technique of embedding discontinuities in continuum thermo-hydro-mechanical elements is capable of reproducing observed features of gas flow migration in clayey rocks. An example is described. It is believed that the developed approach provides a powerful computational procedure to handle complex gas phenomena in clayey rocks. (author)

  4. Radioactivities (dose rates) of rocks in Japan

    International Nuclear Information System (INIS)

    Matsuda, Hideharu; Minato, Susumu

    1995-01-01

    The radioactive distribution (radiation doses) of major rocks in Japan was monitored to clarify the factors influencing terrestrial gamma-ray absorbed dose rates. The rock samples were reduced to powder and analyzed by well-type NaI(Tl) scintillation detector and pulse height analyzer. Terrestrial gamma-ray dose rates were estimated in terms of gamma radiation dose rate 1 m above the ground. The radioactivity concentration was highest in acidic rock which contains much SiO 2 among igneous rock, followed by neutral rock, basic rock, and ultrabasic rock. The radioactive concentration was 30-40% lower in acidic and clastic rocks than those of the world average concentration. Higher radioactive concentration was observed in soils than the parent rocks of sedimentary rock and metamorphic rock. The gamma radiation dose rate was in proportion to the radioactive concentration of the rocks. To clarify the radioactive effect in the change course of rocks into soils, comparative measurement of outcrop and soil radioactive concentrations is important. (S.Y.)

  5. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Science.gov (United States)

    Coque, Emmanuelle; Raoul, Cédric; Bowerman, Mélissa

    2014-01-01

    Spinal muscular atrophy (SMA) is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the Survival Motor Neuron 1 (SMN1) gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK), which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myoblasts, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice. PMID:25221469

  6. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Directory of Open Access Journals (Sweden)

    Emmanuelle eCoque

    2014-08-01

    Full Text Available Spinal muscular atrophy (SMA is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the surviving motor neuron 1 (SMN1 gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK, which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myocytes, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice.

  7. Receptor Tyrosine Kinases in Drosophila Development

    Science.gov (United States)

    Sopko, Richelle; Perrimon, Norbert

    2013-01-01

    Tyrosine phosphorylation plays a significant role in a wide range of cellular processes. The Drosophila genome encodes more than 20 receptor tyrosine kinases and extensive studies in the past 20 years have illustrated their diverse roles and complex signaling mechanisms. Although some receptor tyrosine kinases have highly specific functions, others strikingly are used in rather ubiquitous manners. Receptor tyrosine kinases regulate a broad expanse of processes, ranging from cell survival and proliferation to differentiation and patterning. Remarkably, different receptor tyrosine kinases share many of the same effectors and their hierarchical organization is retained in disparate biological contexts. In this comprehensive review, we summarize what is known regarding each receptor tyrosine kinase during Drosophila development. Astonishingly, very little is known for approximately half of all Drosophila receptor tyrosine kinases. PMID:23732470

  8. Analysis of volcano rocks by Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Sitek, J.; Dekan, J.

    2012-01-01

    In this work we have analysed the basalt rock from Mount Ba tur volcano situated on the Island of Bali in Indonesia.We compared our results with composition of basalt rocks from some other places on the Earth. (authors)

  9. Rock Slope Design Criteria : Executive Summary Report

    Science.gov (United States)

    2010-06-01

    Based on the stratigraphy and the type of slope stability problems, the flat lying, Paleozoic age, sedimentary rocks of Ohio were divided into three design units: 1) competent rock design unit consisting of sandstones, limestones, and siltstones that...

  10. Rock glaciers, Central Andes, Argentina, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — Primary rock glaciers are fed by avalanche chutes. At the El Salto rock glacier, surveys have been undertaken in order to determine the creep rate. Between 1981 and...

  11. Channelling of flow through fractures in rock

    International Nuclear Information System (INIS)

    Bourke, P.J.

    1987-05-01

    A method of mapping the channelling of flow in rock fractures formed by contacts between rock faces and of measuring the effective apertures of channels has been developed. Some typical results are given. (author)

  12. Epigenetic alterations of sedimentary rocks at deposits

    International Nuclear Information System (INIS)

    Komarova, G.V.; Kondrat'eva, I.A.; Zelenova, O.I.

    1980-01-01

    Notions are explained, and technique for studying epigenetic alterations of sedimentary rocks at uranium deposits is described. Main types of epigenetic transformations and their mineralogic-geochemical characteristics are considered. Rock alterations, accompanying uranium mineralization, can be related to 2 types: oxidation and reduction. The main mineralogic-geochemical property of oxidation transformations is epigenetic limonitization. Stratal limonitization in primary grey-coloured terrigenic rocks and in epigenetically reduced (pyritized) rocks, as well as in rock, subjected to epigenetic gleying, are characterized. Reduction type of epigenetic transformations is subdivided into sulphidic and non-sulphidic (gley) subtypes. Sulphidic transformations in grey-coloured terrigenic rocks with organic substance of carbonic row, in rocks, containing organic substance of oil row, sulphide transformations of sedimentary rocks, as well as gley transformations, are considered

  13. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains

    KAUST Repository

    Diaz Galicia, Miriam Escarlet

    2018-01-01

    is then translated into a FRET (Fluorescence Resonance Energy Transfer) signal is here proposed. To this end, DNA constructs for interaction amplification (split kinases), positive controls (intact kinase domains), scaffolding proteins and phosphopeptide - SH2-domain

  14. Analysis of volcano rock from Canary islands

    International Nuclear Information System (INIS)

    Sitek, J.; Sedlackova, K.; Dekan, J.

    2013-01-01

    In this work we have analyzed the basalt rock from Lanzarote, which is the easternmost island of the Canary Islands lying in the Atlantic Ocean and has a volcanic origin. It was born through fiery eruptions and has solidified lava streams as well as extravagant rock formations. We compared our results with composition of basalt rocks from some other places on the Earth. Different iron oxides created on the volcanic rocks during their weathering on the Earth surface has been also analyzed. (authors)

  15. High-pressure mechanical instability in rocks.

    Science.gov (United States)

    Byerlee, J D; Brace, W F

    1969-05-09

    At a confining pressure of a few kilobars, deformation of many sedimentary rocks, altered mafic rocks, porous volcanic rocks, and sand is ductile, in that instabilities leading to audible elastic shocks are absent. At pressures of 7 to 10 kilobars, however, unstable faulting and stick-slip in certain of these rocks was observed. This high pressure-low temperature instability might be responsible for earthquakes in deeply buried sedimentary or volcanic sequences.

  16. Measuring Kinase Activity-A Global Challenge.

    Science.gov (United States)

    Cann, Marissa L; McDonald, Ian M; East, Michael P; Johnson, Gary L; Graves, Lee M

    2017-11-01

    The kinase enzymes within a cell, known collectively as the kinome, play crucial roles in many signaling pathways, including survival, motility, differentiation, stress response, and many more. Aberrant signaling through kinase pathways is often linked to cancer, among other diseases. A major area of scientific research involves understanding the relationships between kinases, their targets, and how the kinome adapts to perturbations of the cellular system. This review will discuss many of the current and developing methods for studying kinase activity, and evaluate their applications, advantages, and disadvantages. J. Cell. Biochem. 118: 3595-3606, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Rock Music's Place in the Library.

    Science.gov (United States)

    Politis, John

    1983-01-01

    Discussion of the importance of rock music as an expression of aural culture includes its history, rock music today, and the development of a rock music collection in the library (placement of collection and books which aid in developing a collection of permanent value). Three references are included. (EJS)

  18. Rock-degrading endophytic bacteria in cacti

    Science.gov (United States)

    M. Esther Puente; Ching Y. Li; Yoav Bashan

    2009-01-01

    A plant-bacterium association of the cardon cactus (Pachycereus pringlei) and endophytic bacteria promotes establishment of seedlings and growth on igneous rocks without soil. These bacteria weather several rock types and minerals, unbind significant amounts of useful minerals for plants from the rocks, fix in vitro N2. produce...

  19. Rock Art: Connecting to the Past.

    Science.gov (United States)

    Knipe, Marianne

    2001-01-01

    Presents an activity for fourth-grade students in which they learn about ancient art and create their own authentic-looking rock sculptures with pictograms, or painted images. Explains how the students create their own rocks and then paint a pictograph on the rocks with brown paint. (CMK)

  20. Engineering of kinase-based protein interacting devices: active expression of tyrosine kinase domains

    KAUST Repository

    Diaz Galicia, Miriam Escarlet

    2018-05-01

    Protein-protein interactions modulate cellular processes in health and disease. However, tracing weak or rare associations or dissociations of proteins is not a trivial task. Kinases are often regulated through interaction partners and, at the same time, themselves regulate cellular interaction networks. The use of kinase domains for creating a synthetic sensor device that reads low concentration protein-protein interactions and amplifies them to a higher concentration interaction which is then translated into a FRET (Fluorescence Resonance Energy Transfer) signal is here proposed. To this end, DNA constructs for interaction amplification (split kinases), positive controls (intact kinase domains), scaffolding proteins and phosphopeptide - SH2-domain modules for the reading of kinase activity were assembled and expression protocols for fusion proteins containing Lyn, Src, and Fak kinase domains in bacterial and in cell-free systems were optimized. Also, two non-overlapping methods for measuring the kinase activity of these proteins were stablished and, finally, a protein-fragment complementation assay with the split-kinase constructs was tested. In conclusion, it has been demonstrated that features such as codon optimization, vector design and expression conditions have an impact on the expression yield and activity of kinase-based proteins. Furthermore, it has been found that the defined PURE cell-free system is insufficient for the active expression of catalytic kinase domains. In contrast, the bacterial co-expression with phosphatases produced active kinase fusion proteins for two out of the three tested Tyrosine kinase domains.

  1. Mechanism of Rock Burst Occurrence in Specially Thick Coal Seam with Rock Parting

    Science.gov (United States)

    Wang, Jian-chao; Jiang, Fu-xing; Meng, Xiang-jun; Wang, Xu-you; Zhu, Si-tao; Feng, Yu

    2016-05-01

    Specially thick coal seam with complex construction, such as rock parting and alternative soft and hard coal, is called specially thick coal seam with rock parting (STCSRP), which easily leads to rock burst during mining. Based on the stress distribution of rock parting zone, this study investigated the mechanism, engineering discriminant conditions, prevention methods, and risk evaluation method of rock burst occurrence in STCSRP through setting up a mechanical model. The main conclusions of this study are as follows. (1) When the mining face moves closer to the rock parting zone, the original non-uniform stress of the rock parting zone and the advancing stress of the mining face are combined to intensify gradually the shearing action of coal near the mining face. When the shearing action reaches a certain degree, rock burst easily occurs near the mining face. (2) Rock burst occurrence in STCSRP is positively associated with mining depth, advancing stress concentration factor of the mining face, thickness of rock parting, bursting liability of coal, thickness ratio of rock parting to coal seam, and difference of elastic modulus between rock parting and coal, whereas negatively associated with shear strength. (3) Technologies of large-diameter drilling, coal seam water injection, and deep hole blasting can reduce advancing stress concentration factor, thickness of rock parting, and difference of elastic modulus between rock parting and coal to lower the risk of rock burst in STCSRP. (4) The research result was applied to evaluate and control the risk of rock burst occurrence in STCSRP.

  2. Kimberley rock art dating project

    International Nuclear Information System (INIS)

    Walsh, G.L.; Morwood, M.

    1997-01-01

    The art's additional value, unequalled by traditionally recognised artefacts, is its permanent pictorial documentation presenting a 'window' into the otherwise intangible elements of perceptions, vision and mind of pre-historic cultures. Unfortunately it's potential in establishing Kimberley archaeological 'big picture' still remains largely unrecognised. Some of findings of the Kimberley Rock Art Dating Project, using AMS and optical stimulated luminescence (OSL) dating techniques, are outlined. It is estimated that these findings will encourage involvement by a greater diversity of specialist disciplines to tie findings into levels of this art sequence as a primary reference point. The sequence represents a sound basis for selecting specific defined images for targeting detailed studies by a range of dating technique. This effectively removes the undesirable ad hoc sampling of 'apparently old paintings'; a process which must unavoidably remain the case with researchers working on most global bodies of rock art

  3. ESR dating of fault rocks

    International Nuclear Information System (INIS)

    Lee, Hee Kwon

    2002-03-01

    Past movement on faults can be dated by measurement of the intensity of ESR signals in quartz. These signals are reset by local lattice deformation and local frictional heating on grain contacts at the time of fault movement. The ESR signals then trow back as a result of bombardment by ionizing radiation from surrounding rocks. The age is obtained from the ratio of the equivalent dose, needed to produce the observed signal, to the dose rate. Fine grains are more completely reset during faulting, and a plot of age vs grain size shows a plateau for grains below critical size : these grains are presumed to have been completely zeroed by the last fault activity. We carried out ESR dating of fault rocks collected from the Yangsan fault system. ESR dates from the this fault system range from 870 to 240 ka. Results of this research suggest that long-term cyclic fault activity continued into the pleistocene

  4. Radionuclide fixation mechanisms in rocks

    International Nuclear Information System (INIS)

    Nakashima, S.

    1991-01-01

    In the safety evaluation of the radioactive waste disposal in geological environment, the mass balance equation for radionuclide migration is given. The sorption of radionuclides by geological formations is conventionally represented by the retardation of the radionuclides as compared with water movement. In order to quantify the sorption of radionuclides by rocks and sediments, the distribution ratio is used. In order to study quantitatively the long term behavior of waste radionuclides in geological environment, besides the distribution ratio concept in short term, slower radionuclide retention reaction involving mineral transformation should be considered. The development of microspectroscopic method for long term reaction path modeling, the behavior of iron during granite and water interaction, the reduction precipitation of radionuclides, radionuclide migration pathways, and the representative scheme of radionuclide migration and fixation in rocks are discussed. (K.I.)

  5. ESR dating of fault rocks

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hee Kwon [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2002-03-15

    Past movement on faults can be dated by measurement of the intensity of ESR signals in quartz. These signals are reset by local lattice deformation and local frictional heating on grain contacts at the time of fault movement. The ESR signals then trow back as a result of bombardment by ionizing radiation from surrounding rocks. The age is obtained from the ratio of the equivalent dose, needed to produce the observed signal, to the dose rate. Fine grains are more completely reset during faulting, and a plot of age vs grain size shows a plateau for grains below critical size : these grains are presumed to have been completely zeroed by the last fault activity. We carried out ESR dating of fault rocks collected from the Yangsan fault system. ESR dates from the this fault system range from 870 to 240 ka. Results of this research suggest that long-term cyclic fault activity continued into the pleistocene.

  6. Relative Permeability of Fractured Rock

    Energy Technology Data Exchange (ETDEWEB)

    Mark D. Habana

    2002-06-30

    Contemporary understanding of multiphase flow through fractures is limited. Different studies using synthetic fractures and various fluids have yielded different relative permeability-saturation relations. This study aimed to extend the understanding of multiphase flow by conducting nitrogen-water relative permeability experiments on a naturally-fractured rock from The Geysers geothermal field. The steady-state approach was used. However, steady state was achieved only at the endpoint saturations. Several difficulties were encountered that are attributed to phase interference and changes in fracture aperture and surface roughness, along with fracture propagation/initiation. Absolute permeabilities were determined using nitrogen and water. The permeability values obtained change with the number of load cycles. Determining the absolute permeability of a core is especially important in a fractured rock. The rock may change as asperities are destroyed and fractures propagate or st rain harden as the net stresses vary. Pressure spikes occurred in water a solute permeability experiments. Conceptual models of an elastic fracture network can explain the pressure spike behavior. At the endpoint saturations the water relative permeabilities obtained are much less than the nitrogen gas relative permeabilities. Saturations were determined by weighing and by resistivity calculations. The resistivity-saturation relationship developed for the core gave saturation values that differ by 5% from the value determined by weighing. Further work is required to complete the relative permeability curve. The steady-state experimental approach encountered difficulties due to phase interference and fracture change. Steady state may not be reached until an impractical length of time. Thus, unsteady-state methods should be pursued. In unsteady-state experiments the challenge will be in quantifying rock fracture change in addition to fluid flow changes.

  7. Mineral and rock chemistry of Mata da Corda Kamafugitic Rocks (Minas Gerais State, Brazil)

    International Nuclear Information System (INIS)

    Albuquerque Sgarbi, Patricia B. de; Valenca, Joel G.

    1995-01-01

    The volcanic rocks of the Mata da Corda Formation (Upper Cretaceous) in Minas Gerais, Brazil, are mafic potassic to ultra potassic rocks of kamafugitic affinity containing essentially clinopyroxenes, perovskite, magnetite and occasionally olivine, phlogopite, melilite pseudomorphs and apatite. The felsic phases are kalsilite and/or leucite pseudomorphs. The rocks are classified as mafitites, leucitites and kalsilitites. The analysis of the available data of the rocks studied, based on the relevant aspects of the main proposals for the classification of alkaline mafic to ultramafic potassic rocks leads to the conclusion that Sahama's (1974) proposal to divide potassium rich alkaline rocks in two large families is the one to which the Mata da Corda rocks adapt best. According to this and the data in the literature on the mineralogy and mineral and rock chemistries of the other similar occurrences, these rocks may be interpreted as alkaline potassic to ultra potassic rocks of hamafugitic affinity. 11 figs., 5 tabs

  8. ESR dating of fault rocks

    International Nuclear Information System (INIS)

    Lee, Hee Kwon

    2003-02-01

    Past movement on faults can be dated by measurement of the intensity of ESR signals in quartz. These signals are reset by local lattice deformation and local frictional heating on grain contacts at the time of fault movement. The ESR signals then grow back as a result of bombardment by ionizing radiation from surrounding rocks. The age is obtained from the ratio of the equivalent dose, needed to produce the observed signal, to the dose rate. Fine grains are more completely reset during faulting, and a plot of age vs. grain size shows a plateau for grains below critical size; these grains are presumed to have been completely zeroed by the last fault activity. We carried out ESR dating of fault rocks collected near the Gori nuclear reactor. Most of the ESR signals of fault rocks collected from the basement are saturated. This indicates that the last movement of the faults had occurred before the Quaternary period. However, ESR dates from the Oyong fault zone range from 370 to 310 ka. Results of this research suggest that long-term cyclic fault activity of the Oyong fault zone continued into the Pleistocene

  9. ESR dating of fault rocks

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hee Kwon [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2003-02-15

    Past movement on faults can be dated by measurement of the intensity of ESR signals in quartz. These signals are reset by local lattice deformation and local frictional heating on grain contacts at the time of fault movement. The ESR signals then grow back as a result of bombardment by ionizing radiation from surrounding rocks. The age is obtained from the ratio of the equivalent dose, needed to produce the observed signal, to the dose rate. Fine grains are more completely reset during faulting, and a plot of age vs. grain size shows a plateau for grains below critical size; these grains are presumed to have been completely zeroed by the last fault activity. We carried out ESR dating of fault rocks collected near the Gori nuclear reactor. Most of the ESR signals of fault rocks collected from the basement are saturated. This indicates that the last movement of the faults had occurred before the Quaternary period. However, ESR dates from the Oyong fault zone range from 370 to 310 ka. Results of this research suggest that long-term cyclic fault activity of the Oyong fault zone continued into the Pleistocene.

  10. Source rock hydrocarbons. Present status

    International Nuclear Information System (INIS)

    Vially, R.; Maisonnier, G.; Rouaud, T.

    2013-01-01

    This report first presents the characteristics of conventional oil and gas system, and the classification of liquid and gaseous non conventional hydrocarbons, with the peculiar case of coal-bed methane. The authors then describe how source rock hydrocarbons are produced: production of shale oils and gases (horizontal drilling, hydraulic fracturing, exploitation) and of coal-bed methane and coal mine methane. In the next part, they address and discuss the environmental impact of source rock hydrocarbon production: installation footprint, water resource management, drilling fluids, fracturing fluids composition, toxicity and recycling, air pollution, induced seismicity, pollutions from other exploitation and production activities. They propose an overview of the exploitation and production of source rock gas, coal-bed gas and other non conventional gases in the world. They describe the current development and discuss their economic impacts: world oil context and trends in the USA, in Canada and other countries, impacts on the North American market, on the world oil industry, on refining industries, on the world oil balance. They analyse the economic impacts of non conventional gases: development potential, stakes for the world gas trade, consequence for gas prices, development opportunities for oil companies and for the transport sector, impact on CO 2 emissions, macro-economic impact in the case of the USA

  11. Fasudil, a Clinically Used ROCK Inhibitor, Stabilizes Rod Photoreceptor Synapses after Retinal Detachment.

    Science.gov (United States)

    Townes-Anderson, Ellen; Wang, Jianfeng; Halász, Éva; Sugino, Ilene; Pitler, Amy; Whitehead, Ian; Zarbin, Marco

    2017-06-01

    Retinal detachment disrupts the rod-bipolar synapse in the outer plexiform layer by retraction of rod axons. We showed that breakage is due to RhoA activation whereas inhibition of Rho kinase (ROCK), using Y27632, reduces synaptic damage. We test whether the ROCK inhibitor fasudil, used for other clinical applications, can prevent synaptic injury after detachment. Detachments were made in pigs by subretinal injection of balanced salt solution (BSS) or fasudil (1, 10 mM). In some animals, fasudil was injected intravitreally after BSS-induced detachment. After 2 to 4 hours, retinae were fixed for immunocytochemistry and confocal microscopy. Axon retraction was quantified by imaging synaptic vesicle label in the outer nuclear layer. Apoptosis was analyzed using propidium iodide staining. For biochemical analysis by Western blotting, retinal explants, detached from retinal pigmented epithelium, were cultured for 2 hours. Subretinal injection of fasudil (10 mM) reduced retraction of rod spherules by 51.3% compared to control detachments ( n = 3 pigs, P = 0.002). Intravitreal injection of 10 mM fasudil, a more clinically feasible route of administration, also reduced retraction (28.7%, n = 5, P ROCK, was decreased with 30 μM fasudil ( n = 8-10 explants, P ROCK signaling with fasudil reduced photoreceptor degeneration and preserved the rod-bipolar synapse after retinal detachment. These results support the possibility, previously tested with Y27632, that ROCK inhibition may attenuate synaptic damage in iatrogenic detachments.

  12. A Review on the British Rock Music

    OpenAIRE

    Hutapea, Alfian Hadi Pranata

    2011-01-01

    Music has an important role in people’s life. In people’s daily, music is often hearing of course and in people’s customs and traditions music is also be used. Music has many genres, one of them is rock music. Many people like rock music especially youngman because rock music has given a message in a song through enthusiasm expression. Rock music has many subgenres and each of subgenres have a distinctive feature. The developing of rock music is very wide in the world, especially in Great Bri...

  13. The physical principles of rock magnetism

    CERN Document Server

    Stacey, Frank

    1974-01-01

    Developments in Solid Earth Geophysics 5: The Physical Principles of Rock Magnetism explores the physical principles of rock magnetism, with emphasis on the properties of finely divided magnetic materials. It discusses the origin and stability of rock magnetizations, the role of remanent magnetism in interpreting magnetic surveys, magnetic anisotropy as an indicator of rock fabric, and the relationship between piezomagnetic changes and seismic activity. Organized into 13 chapters, this volume discusses the properties of solids, magnetite and hematite grains, and rocks with magnetite grains

  14. Effects of explosions in hard rocks

    International Nuclear Information System (INIS)

    Heuze, F.E.; Walton, O.R.; Maddix, D.M.; Shaffer, R.J.; Butkovich, T.R.

    1993-01-01

    This work relates to explosions in hard rocks (ex: basalt, granite, limestone...). Hard rock masses typically have a blocky structure created by the existence of geologic discontinuities such as bedding contacts, faults, and joints. At very high pressure - hundreds of kilobars and above - these discontinuities do not act separately, and the rock appears to be an equivalent continuous medium. At stress of a few tens of kilobars and below, the geologic discontinuities control the kinematics of the rock masses. Hence, the simulation of rock dynamics, anywhere but in the very-near source region, should account for those kinematics

  15. Lead isotope analyses of standard rock samples

    International Nuclear Information System (INIS)

    Koide, Yoshiyuki; Nakamura, Eizo

    1990-01-01

    New results on lead isotope compositions of standard rock samples and their analytical procedures are reported. Bromide form anion exchange chromatography technique was adopted for the chemical separation lead from rock samples. The lead contamination during whole analytical procedure was low enough to determine lead isotope composition of common natural rocks. Silica-gel activator method was applied for emission of lead ions in the mass spectrometer. Using the data reduction of 'unfractionated ratios', we obtained good reproducibility, precision and accuracy on lead isotope compositions of NBS SRM. Here we present new reliable lead isotope compositions of GSJ standard rock samples and USGS standard rock, BCR-1. (author)

  16. Oncogenic Receptor Tyrosine Kinases Directly Phosphorylate Focal Adhesion Kinase (FAK) as a Resistance Mechanism to FAK-Kinase Inhibitors.

    Science.gov (United States)

    Marlowe, Timothy A; Lenzo, Felicia L; Figel, Sheila A; Grapes, Abigail T; Cance, William G

    2016-12-01

    Focal adhesion kinase (FAK) is a major drug target in cancer and current inhibitors targeted to the ATP-binding pocket of the kinase domain have entered clinical trials. However, preliminary results have shown limited single-agent efficacy in patients. Despite these unfavorable data, the molecular mechanisms that drive intrinsic and acquired resistance to FAK-kinase inhibitors are largely unknown. We have demonstrated that receptor tyrosine kinases (RTK) can directly bypass FAK-kinase inhibition in cancer cells through phosphorylation of FAK's critical tyrosine 397 (Y397). We also showed that HER2 forms a direct protein-protein interaction with the FAK-FERM-F1 lobe, promoting direct phosphorylation of Y397. In addition, FAK-kinase inhibition induced two forms of compensatory RTK reprogramming: (i) the rapid phosphorylation and activation of RTK signaling pathways in RTK High cells and (ii) the long-term acquisition of RTKs novel to the parental cell line in RTK Low cells. Finally, HER2 +: cancer cells displayed resistance to FAK-kinase inhibition in 3D growth assays using a HER2 isogenic system and HER2 + cancer cell lines. Our data indicate a novel drug resistance mechanism to FAK-kinase inhibitors whereby HER2 and other RTKs can rescue and maintain FAK activation (pY397) even in the presence of FAK-kinase inhibition. These data may have important ramifications for existing clinical trials of FAK inhibitors and suggest that individual tumor stratification by RTK expression would be important to predict patient response to FAK-kinase inhibitors. Mol Cancer Ther; 15(12); 3028-39. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Rock Tea extract (Jasonia glutinosa) relaxes rat aortic smooth muscle by inhibition of L-type Ca(2+) channels.

    Science.gov (United States)

    Valero, Marta Sofía; Oliván-Viguera, Aida; Garrido, Irene; Langa, Elisa; Berzosa, César; López, Víctor; Gómez-Rincón, Carlota; Murillo, María Divina; Köhler, Ralf

    2015-12-01

    In traditional herbal medicine, Rock Tea (Jasonia glutinosa) is known for its prophylactic and therapeutic value in various disorders including arterial hypertension. However, the mechanism by which Rock Tea exerts blood pressure-lowering actions has not been elucidated yet. Our aim was to demonstrate vasorelaxing effects of Rock Tea extract and to reveal its possible action mechanism. Isometric myography was conducted on high-K+-precontracted rings from rat thoracic aorta and tested extracts at concentrations of 0.5-5 mg/ml. Whole-cell patch-clamp experiments were performed in rat aortic vascular smooth muscle cells (line A7r5) to determine blocking effects on L-type Ca(2+) channels. Rock Tea extract relaxed the aorta contracted by high [K+] concentration dependently with an EC50 of ≈2.4 mg/ml and produced ≈75 % relaxation at the highest concentration tested. The L-type Ca(2+) channel blocker, verapamil (10(-6) M), had similar effects. Rock Tea extract had no effect in nominally Ca(2+)-free high-K(+) buffer but significantly inhibited contractions to re-addition of Ca(2+). Rock Tea extract inhibited the contractions induced by the L-type Ca(2+) channel activator Bay K 8644 (10(-5) M) and by phenylephrine (10(-6) M). Rock Tea extract and Y-27632 (10(-6) M), Rho-kinase inhibitor, had similar effects and the respective effects were not additive. Patch-clamp experiments demonstrated that Rock Tea extract (2.5 mg/ml) virtually abolished L-type Ca(2+) currents in A7r5. We conclude that Rock Tea extract produced vasorelaxation of rat aorta and that this relaxant effect is mediated by inhibition of L-type Ca(2+) channels. Rock Tea extracts may be of phytomedicinal value for prevention and adjuvant treatment of hypertension and other cardiovascular diseases.

  18. A rice kinase-protein interaction map.

    Science.gov (United States)

    Ding, Xiaodong; Richter, Todd; Chen, Mei; Fujii, Hiroaki; Seo, Young Su; Xie, Mingtang; Zheng, Xianwu; Kanrar, Siddhartha; Stevenson, Rebecca A; Dardick, Christopher; Li, Ying; Jiang, Hao; Zhang, Yan; Yu, Fahong; Bartley, Laura E; Chern, Mawsheng; Bart, Rebecca; Chen, Xiuhua; Zhu, Lihuang; Farmerie, William G; Gribskov, Michael; Zhu, Jian-Kang; Fromm, Michael E; Ronald, Pamela C; Song, Wen-Yuan

    2009-03-01

    Plants uniquely contain large numbers of protein kinases, and for the vast majority of the 1,429 kinases predicted in the rice (Oryza sativa) genome, little is known of their functions. Genetic approaches often fail to produce observable phenotypes; thus, new strategies are needed to delineate kinase function. We previously developed a cost-effective high-throughput yeast two-hybrid system. Using this system, we have generated a protein interaction map of 116 representative rice kinases and 254 of their interacting proteins. Overall, the resulting interaction map supports a large number of known or predicted kinase-protein interactions from both plants and animals and reveals many new functional insights. Notably, we found a potential widespread role for E3 ubiquitin ligases in pathogen defense signaling mediated by receptor-like kinases, particularly by the kinases that may have evolved from recently expanded kinase subfamilies in rice. We anticipate that the data provided here will serve as a foundation for targeted functional studies in rice and other plants. The application of yeast two-hybrid and TAPtag analyses for large-scale plant protein interaction studies is also discussed.

  19. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases Summary

    The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase

  20. Diffusion in the matrix of granitic rock

    International Nuclear Information System (INIS)

    Birgersson, L.; Neretnieks, I.

    1982-07-01

    A migration experiment in the rock matrix is presented. The experiment has been carried out in undisturbed rock, that is rock under its natural stress environment. Since the experiment was performed at the 360 m-level (in the Stripa mine), the rock had nearly the same conditions as the rock surrounding a nuclear waste storage. The results show that all three tracers (Uranine, Cr-EDTA and I - ) have passed the disturbed zone from the injection hole and migrated into undisturbed rock. At the distance of 11 cm from the injection hole 5-10 percent of the injection concentration was found. The results also indicate that the tracer have passed through fissure filling material. These results indicate that it is possible for tracers (and therefore radionuclides) to migrate from a fissure, through fissure filling material, and into the undisturbed rock matrix. (Authors)

  1. Carbonate rock depositional models: A microfacies approach

    Energy Technology Data Exchange (ETDEWEB)

    Carozzi, A.V.

    1988-01-01

    Carbonate rocks contain more than 50% by weight carbonate minerals such as calcite, dolomite, and siderite. Understanding how these rocks form can lead to more efficient methods of petroleum exploration. Micofacies analysis techniques can be used as a method of predicting models of sedimentation for carbonate rocks. Micofacies in carbonate rocks can be seen clearly only in thin sections under a microscope. This section analysis of carbonate rocks is a tool that can be used to understand depositional environments, diagenetic evolution of carbonate rocks, and the formation of porosity and permeability in carbonate rocks. The use of micofacies analysis techniques is applied to understanding the origin and formation of carbonate ramps, carbonate platforms, and carbonate slopes and basins. This book will be of interest to students and professionals concerned with the disciplines of sedimentary petrology, sedimentology, petroleum geology, and palentology.

  2. dependent/calmodulin- stimulated protein kinase from moss

    Indian Academy of Sciences (India)

    Unknown

    stimulated protein kinase; CDPK, calmodulin domain-like protein kinase; KM14, 14 amino acid synthetic peptide; .... used were obtained from Sigma Chemical Company, USA, ..... Plant chimeric Ca2+/Calmodulin-dependent protein kinase.

  3. The Protein Kinase RSK Family - Roles in Prostate Cancer

    National Research Council Canada - National Science Library

    Lannigan, Deborah

    2006-01-01

    The Ser/Thr protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of mitogen-activated protein kinase but its roles in prostate cancer have not been previously examined...

  4. Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

    Science.gov (United States)

    Filippakopoulos, Panagis; Kofler, Michael; Hantschel, Oliver; Gish, Gerald D; Grebien, Florian; Salah, Eidarus; Neudecker, Philipp; Kay, Lewis E; Turk, Benjamin E; Superti-Furga, Giulio; Pawson, Tony; Knapp, Stefan

    2008-09-05

    The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

  5. Glycogen Synthase Kinase-3β

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Lenskjold, Toke; Jacoby, Anne Sophie

    2016-01-01

    cells were quantitated using enzyme immunometric assays. The activity of GSK-3β (serine-9-phosphorylated GSK-3β/total GSK-3β) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3β and serine-9-phosphorylated GSK-3β. Exploratory......Evidence indicates a role for glycogen synthase kinase-3β (GSK-3β) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3β activity over time is unknown. We aimed to investigate GSK-3β activity over time and its possible correlation...... with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3β and serine-9-phosphorylated GSK-3β in peripheral blood mononuclear...

  6. TYROSINE KINASE INHIBITORS AND PREGNANCY

    Directory of Open Access Journals (Sweden)

    Elisabetta Abruzzese

    2014-04-01

    Full Text Available The management of patients with chronic myeloid leukemia (CML during pregnancy has became recently a matter of continuous debate.  The introduction of the Tyrosine Kinase Inhibitors (TKIs in clinical practice has dramatically changed the prognosis of CML patients.  Patients diagnosed in chronic phase can reasonably expect many years of excellent disease control and good quality of life, as well as a normal life expectancy.  This fact has come the necessity to address issues relating to fertility and pregnancy. Physicians are not infrequently being asked for advice regarding the need for, and or the appropriateness of, stopping treatment in order to conceive. In this report we will review the data published in terms of fertility, conception, pregnancy, pregnancy outcome and illness control for all the approved TKIs, as well as suggest how to manage a planned and/or unplanned pregnancy.

  7. Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats.

    Science.gov (United States)

    Shiotani, Satoko; Shimada, Mitsuo; Suehiro, Taketoshi; Soejima, Yuji; Yosizumi, Tomoharu; Shimokawa, Hiroaki; Maehara, Yoshihiko

    2004-08-15

    Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.

  8. Hot Dry Rock; Geothermal Energy

    Energy Technology Data Exchange (ETDEWEB)

    None

    1990-01-01

    The commercial utilization of geothermal energy forms the basis of the largest renewable energy industry in the world. More than 5000 Mw of electrical power are currently in production from approximately 210 plants and 10 000 Mw thermal are used in direct use processes. The majority of these systems are located in the well defined geothermal generally associated with crustal plate boundaries or hot spots. The essential requirements of high subsurface temperature with huge volumes of exploitable fluids, coupled to environmental and market factors, limit the choice of suitable sites significantly. The Hot Dry Rock (HDR) concept at any depth originally offered a dream of unlimited expansion for the geothermal industry by relaxing the location constraints by drilling deep enough to reach adequate temperatures. Now, after 20 years intensive work by international teams and expenditures of more than $250 million, it is vital to review the position of HDR in relation to the established geothermal industry. The HDR resource is merely a body of rock at elevated temperatures with insufficient fluids in place to enable the heat to be extracted without the need for injection wells. All of the major field experiments in HDR have shown that the natural fracture systems form the heat transfer surfaces and that it is these fractures that must be for geothermal systems producing from naturally fractured formations provide a basis for directing the forthcoming but, equally, they require accepting significant location constraints on HDR for the time being. This paper presents a model HDR system designed for commercial operations in the UK and uses production data from hydrothermal systems in Japan and the USA to demonstrate the reservoir performance requirements for viable operations. It is shown that these characteristics are not likely to be achieved in host rocks without stimulation processes. However, the long term goal of artificial geothermal systems developed by systematic

  9. Hydraulic testing in crystalline rock

    International Nuclear Information System (INIS)

    Almen, K.E.; Andersson, J.E.; Carlsson, L.; Hansson, K.; Larsson, N.A.

    1986-12-01

    Swedish Geolocical Company (SGAB) conducted and carried out single-hole hydraulic testing in borehole Fi 6 in the Finnsjoen area of central Sweden. The purpose was to make a comprehensive evaluation of different methods applicable in crystalline rocks and to recommend methods for use in current and scheduled investigations in a range of low hydraulic conductivity rocks. A total of eight different methods of testing were compared using the same equipment. This equipment was thoroughly tested as regards the elasticity of the packers and change in volume of the test section. The use of a hydraulically operated down-hole valve enabled all the tests to be conducted. Twelve different 3-m long sections were tested. The hydraulic conductivity calculated ranged from about 5x10 -14 m/s to 1x10 -6 m/s. The methods used were water injection under constant head and then at a constant rate-of-flow, each of which was followed by a pressure fall-off period. Water loss, pressure pulse, slug and drill stem tests were also performed. Interpretation was carried out using standard transient evaluation methods for flow in porous media. The methods used showed themselves to be best suited to specific conductivity ranges. Among the less time-consuming methods, water loss, slug and drill stem tests usually gave somewhat higher hydraulic conductivity values but still comparable to those obtained using the more time-consuming tests. These latter tests, however, provided supplementary information on hydraulic and physical properties and flow conditions, together with hydraulic conductivity values representing a larger volume of rock. (orig./HP)

  10. Big Bang Day : Physics Rocks

    CERN Multimedia

    Brian Cox; John Barrowman; Eddie Izzard

    2008-01-01

    Is particle physics the new rock 'n' roll? The fundamental questions about the nature of the universe that particle physics hopes to answer have attracted the attention of some very high profile and unusual fans. Alan Alda, Ben Miller, Eddie Izzard, Dara O'Briain and John Barrowman all have interests in this branch of physics. Brian Cox - CERN physicist, and former member of 90's band D:Ream, tracks down some very well known celebrity enthusiasts and takes a light-hearted look at why this subject can appeal to all of us.

  11. ROCKS & MINERALS DETERMINATION AND ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    20150204 Abaydulla Alimjan(Department of Chemistry and Environmental Sciences,Kashgar Teachers College,Kashgar 844006,China);Cheng Chunying Non-Metallic Element Composition Analysis of Non-Ferrous Metal Ores from Oytagh Town,Xinjiang(Rock and Mineral Analysis,ISSN0254-5357,CN11-2131/TD,33(1),2014,p.44-50,5illus.,4tables,28refs.)Key words:nonferrous metals ore,nonmetals,chemical analysis,thermogravimetric analysis Anions in non-ferrous ore materials

  12. Rock Goes to School on Screen: A Model for Teaching Non-"Learned" Musics Derived from the Films "School of Rock" (2003) and "Rock School" (2005)

    Science.gov (United States)

    Webb, Michael

    2007-01-01

    What can be learned from two films with "rock" and "school" in their titles, about rock in school and about music and schooling more broadly? "School of Rock" (2003), a "family comedy," and "Rock School" (2005), a documentary, provoke a range of questions, ideological and otherwise, surrounding the inclusion of rock in formal instructional…

  13. A chemically defined culture medium containing Rho kinase inhibitor Y-27632 for the fabrication of stratified squamous epithelial cell grafts

    Energy Technology Data Exchange (ETDEWEB)

    Aslanova, Afag [Department of Surgery, Institute of Gastroenterology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Institute of Advanced Biomedical Engineering and Science, Tokyo Women' s Medical University, TWIns, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Takagi, Ryo; Yamato, Masayuki; Okano, Teruo [Institute of Advanced Biomedical Engineering and Science, Tokyo Women' s Medical University, TWIns, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Yamamoto, Masakazu, E-mail: yamamoto.ige@twmu.ac.jp [Department of Surgery, Institute of Gastroenterology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)

    2015-05-01

    With the development of a culture method for stratified squamous epithelial cells, tissue-engineered epithelial cell sheets have been successfully applied as clinical cell grafts. However, the implementation of these cell sheets without the use of any animal-derived materials is highly desirable. In this study, Rho-associated protein kinase inhibitor Y-27632 was used to develop a chemically defined culture medium for the fabrication of stratified epithelial cell grafts consisting of human epidermal and oral keratinocytes, and the proliferation activity, cell morphology, and gene expressions of the keratinocytes were analyzed. The results of a colorimetric assay indicated that Y-27632 significantly promoted the proliferation of the keratinocytes in culture media both with and without fetal bovine serum (FBS), although there were no indications of Y-27632 efficacy on cell morphology and stratification of the keratinocytes in culture medium without any animal-derived materials. The results of quantitative RT-PCR revealed that gene expressions correlated with cell adhesion, cell–cell junction, proliferation markers, and stem/progenitor markers in cultured keratinocytes were not strongly affected by the addition of Y-27632 to the culture medium. Moreover, gene expressions of differentiation markers in stratified keratinocytes cultured in medium without FBS were nearly identical to those of keratinocytes co-cultured with 3T3 feeder cells. Interestingly, the expressions of differentiation markers in cultured stratified keratinocytes were suppressed by FBS, whereas they were reconstructed by either co-culture of a 3T3 feeder layer or addition of Y-27632 into the culture medium containing FBS. These findings indicate that Y-27632 is a useful supplement for the development of a chemically defined culture medium for fabrication of stratified epithelial cell grafts for clinical applications for the purpose of developing the culture medium with a lower risk of pathogen

  14. A chemically defined culture medium containing Rho kinase inhibitor Y-27632 for the fabrication of stratified squamous epithelial cell grafts

    International Nuclear Information System (INIS)

    Aslanova, Afag; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Yamamoto, Masakazu

    2015-01-01

    With the development of a culture method for stratified squamous epithelial cells, tissue-engineered epithelial cell sheets have been successfully applied as clinical cell grafts. However, the implementation of these cell sheets without the use of any animal-derived materials is highly desirable. In this study, Rho-associated protein kinase inhibitor Y-27632 was used to develop a chemically defined culture medium for the fabrication of stratified epithelial cell grafts consisting of human epidermal and oral keratinocytes, and the proliferation activity, cell morphology, and gene expressions of the keratinocytes were analyzed. The results of a colorimetric assay indicated that Y-27632 significantly promoted the proliferation of the keratinocytes in culture media both with and without fetal bovine serum (FBS), although there were no indications of Y-27632 efficacy on cell morphology and stratification of the keratinocytes in culture medium without any animal-derived materials. The results of quantitative RT-PCR revealed that gene expressions correlated with cell adhesion, cell–cell junction, proliferation markers, and stem/progenitor markers in cultured keratinocytes were not strongly affected by the addition of Y-27632 to the culture medium. Moreover, gene expressions of differentiation markers in stratified keratinocytes cultured in medium without FBS were nearly identical to those of keratinocytes co-cultured with 3T3 feeder cells. Interestingly, the expressions of differentiation markers in cultured stratified keratinocytes were suppressed by FBS, whereas they were reconstructed by either co-culture of a 3T3 feeder layer or addition of Y-27632 into the culture medium containing FBS. These findings indicate that Y-27632 is a useful supplement for the development of a chemically defined culture medium for fabrication of stratified epithelial cell grafts for clinical applications for the purpose of developing the culture medium with a lower risk of pathogen

  15. Radon exhalation from granitic rocks

    International Nuclear Information System (INIS)

    Del Claro, Flávia; Paschuk, Sergei A.; Corrêa, Janine N.; Mazer, Wellington; Narloch, Danielle Cristine; Martin, Aline Cristina; Denyak, Valeriy

    2017-01-01

    Naturally occurring radionuclides such as radon ( 222 Rn), its decay products and other elements from the radioactive series of uranium ( 238 U and 235 U) and thorium ( 232 Th) are an important source of human exposure to natural radioactivity. The worldwide evaluation of health radiobiological effects and risks from population exposure to natural radionuclides is a growing concern. About 50% of personal radiation annual dose is related to radionuclides such as radon ( 222 Rn), thoron ( 220 Rn), radium ( 226 Ra), thorium ( 232 Th) and potassium ( 40 K), which are present in modern materials commonly used in construction of dwellings and buildings. The radioactivity of marbles and granites is of big concern since under certain conditions the radioactivity levels of these materials can be hazardous to the population and require the implementation of mitigation procedures. Present survey of the 222 Rn and 220 Rn activity concentration liberated in the air was performed using commercialized Brazilian granite rocks at national market as well as exported to other countries. The 222 Rn and 220 Rn measurements were performed using the AlphaGUARD instant monitor and RAD7 detector, respectively. This study was performed at the Applied Nuclear Physics Laboratory of the Federal University of Technology – Paraná (UTFPR). Obtained results of radon concentration activity in air exhaled studied samples of granites varied from 3±1 Bq/m 3 to 2087±19 Bq/m 3 , which shows that some samples of granitic rocks represent rather elevated health risk the population. (author)

  16. Hydraulic gradients in rock aquifers

    International Nuclear Information System (INIS)

    Dahlblom, P.

    1992-05-01

    This report deals with fractured rock as a host for deposits of hazardous waste. In this context the rock, with its fractures containing moving groundwater, is called the geological barrier. The desired properties of the geological barrier are low permeability to water, low hydraulic gradients and ability to retain matter dissolved in the water. The hydraulic gradient together with the permeability and the porosity determines the migration velocity. Mathematical modelling of the migration involves calculation of the water flow and the hydrodynamic dispersion of the contaminant. The porous medium approach can be used to calculate mean flow velocities and hydrodynamic dispersion of a large number of fractures are connected, which means that a large volume have to be considered. It is assumed that the porous medium approach can be applied, and a number of idealized examples are shown. It is assumed that the groundwater table is replenished by percolation at a constant rate. One-dimensional analytical calculations show that zero hydraulic gradients may exist at relatively large distance from the coast. Two-dimensional numerical calculations show that it may be possible to find areas with low hydraulic gradients and flow velocities within blocks surrounded by areas with high hydraulic conductivity. (au)

  17. Laboratory characterization of rock joints

    International Nuclear Information System (INIS)

    Hsiung, S.M.; Kana, D.D.; Ahola, M.P.; Chowdhury, A.H.; Ghosh, A.

    1994-05-01

    A laboratory characterization of the Apache Leap tuff joints under cyclic pseudostatic and dynamic loads has been undertaken to obtain a better understanding of dynamic joint shear behavior and to generate a complete data set that can be used for validation of existing rock-joint models. Study has indicated that available methods for determining joint roughness coefficient (JRC) significantly underestimate the roughness coefficient of the Apache Leap tuff joints, that will lead to an underestimation of the joint shear strength. The results of the direct shear tests have indicated that both under cyclic pseudostatic and dynamic loadings the joint resistance upon reverse shearing is smaller than that of forward shearing and the joint dilation resulting from forward shearing recovers during reverse shearing. Within the range of variation of shearing velocity used in these tests, the shearing velocity effect on rock-joint behavior seems to be minor, and no noticeable effect on the peak joint shear strength and the joint shear strength for the reverse shearing is observed

  18. Aespoe hard rock laboratory Sweden

    International Nuclear Information System (INIS)

    1992-01-01

    The aim of the new Aespoe hard rock laboratory is to demonstrate state of the art of technology and evaluation methods before the start of actual construction work on the planned deep repository for spent nuclear fuel. The nine country OECD/NEA project in the Stripa mine in Sweden has been an excellent example of high quality international research co-operation. In Sweden the new Aespoe hard rock laboratory will gradually take over and finalize this work. SKB very much appreciates the continued international participation in Aespoe which is of great value for the quality efficiency, and confidence in this kind of work. We have invited a number of leading experts to this first international seminar to summarize the current state of a number of key questions. The contributions show the great progress that has taken place during the years. The results show that there is a solid scientific basis for using this knowledge on site specific preparation and work on actual repositories. (au)

  19. Proceedings of the 3. Canada-US rock mechanics symposium and 20. Canadian rock mechanics symposium : rock engineering 2009 : rock engineering in difficult conditions

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-01

    This conference provided a forum for geologists, mining operators and engineers to discuss the application of rock mechanics in engineering designs. Members of the scientific and engineering communities discussed challenges and interdisciplinary elements involved in rock engineering. New geological models and methods of characterizing rock masses and ground conditions in underground engineering projects were discussed along with excavation and mining methods. Papers presented at the conference discussed the role of rock mechanics in forensic engineering. Geophysics, geomechanics, and risk-based approaches to rock engineering designs were reviewed. Issues related to high pressure and high flow water conditions were discussed, and new rock physics models designed to enhance hydrocarbon recovery were presented. The conference featured 84 presentations, of which 9 have been catalogued separately for inclusion in this database. tabs., figs.

  20. Chemical buffering capacity of clay rock

    International Nuclear Information System (INIS)

    Beaucaire, C.; Pearson, F.J.; Gautschi, A.

    2004-01-01

    The long-term performance of a nuclear waste repository is strongly dependent on the chemical properties of the host rock. The host rock establishes the chemical environment that determines such important performance attributes as radionuclide solubilities from the waste and the transport rates from the repository to the accessible environment. Clay-rich rocks are especially favourable host rocks because they provide a strong buffering capacity to resist chemical changes prompted either internally, by reactions of the waste itself and emplacement materials, or externally, by changes in the hydrologic systems surrounding the host rock. This paper will focus on three aspects of the stability of clay-rich host rocks: their ability to provide pCO 2 and redox buffering, and to resist chemical changes imposed by changes in regional hydrology and hydro-chemistry. (authors)

  1. Radiation transport in statistically inhomogeneous rocks

    International Nuclear Information System (INIS)

    Lukhminskij, B.E.

    1975-01-01

    A study has been made of radiation transfer in statistically inhomogeneous rocks. Account has been taken of the statistical character of rock composition through randomization of density. Formulas are summarized for sigma-distribution, homogeneous density, the Simpson and Cauchy distributions. Consideration is given to the statistics of mean square ranges in a medium, simulated by the jump Markov random function. A quantitative criterion of rock heterogeneity is proposed

  2. Response of rocks to large stresses

    International Nuclear Information System (INIS)

    Schock, R.N.

    1976-01-01

    To predict the dimensions and characteristics of impact- and explosion-induced craters, one must know the equation of state of the rocks in which the crater is formed. Recent experimental data shed light upon inelastic processes that influence the stress/strain behavior of rocks. We examine these data with a view to developing models that could be used in predicting cratering phenomena. New data is presented on the volume behavior of two dissimilar rocks subjected to tensile stresses

  3. Rock breaking methods to replace blasting

    Science.gov (United States)

    Zhou, Huisheng; Xie, Xinghua; Feng, Yuqing

    2018-03-01

    The method of breaking rock by blasting has a high efficiency and the cost is relatively low, but the associated vibration, flyrock, production of toxic gases since the 1970’s, the Western developed countries began to study the safety of breaking rock. This paper introduces different methods and their progress to safely break rock. Ideally, safe rock breaking would have little vibration, no fly stone, and no toxic gases, which can be widely used in municipal engineering, road excavation, high-risk mining, quarrying and complex environment.

  4. Hopi and Anasazi Alignments and Rock Art

    Science.gov (United States)

    Bates, Bryan C.

    The interaction of light and shadow on ancestral Puebloan rock art, or rock art demarcating sunrise/set horizon points that align with culturally significant dates, has long been assumed to be evidence of "intentional construct" for marking time or event by the native creator. However, anthropological rock art research requires the scientific control of cultural time, element orientation and placement, structure, and association with other rock art elements. The evaluation of five exemplars challenges the oft-held assumption that "if the interaction occurs, it therefore supports intentional construct" and thereby conveys meaning to the native culture.

  5. Professional users handbook for rock bolting

    Energy Technology Data Exchange (ETDEWEB)

    Stillborg, B.

    1986-01-01

    The paper is a practical handbook which reviews the basic principles of rock bolting and sets out the design considerations used for most types of rockbolts in current use. It discusses the characteristics of these bolts and gives information on installation procedures and the observations and measurement of rockbolt performance. Rockbolting is considered under the following chapter headings: review of typical rockbolt systems; rockbolt installation; testing of rockbolts; design considerations; design of rock reinforcement; monitoring; cost of rock bolting; and Atlas Lopco auxillary equipment for rock bolting. 45 refs.

  6. Tunnel Design by Rock Mass Classifications

    Science.gov (United States)

    1990-01-01

    Engineering," revised second edition, Institution of Mining and Metallurgy, London, 1977, pp 113-115 and 150-192. 42. Selmer - Olsen , R., and Broch, E...to wall when a)/03 > 10, re- stability) ................ 10-5 0.66-0.33 0.5-2.0 duce oc and ot to L. Mild rock burst (massive 0.6 cc and 0.6 on rock ...5-2.5 0.33-0.16 5-10 where: 0 c = uncon-fined compression M. Heavy rock burst (massive strength, at = rock

  7. Igneous rocks formed by hypervelocity impact

    Science.gov (United States)

    Osinski, Gordon R.; Grieve, Richard A. F.; Bleacher, Jacob E.; Neish, Catherine D.; Pilles, Eric A.; Tornabene, Livio L.

    2018-03-01

    Igneous rocks are the primary building blocks of planetary crusts. Most igneous rocks originate via decompression melting and/or wet melting of protolith lithologies within planetary interiors and their classification and compositional, petrographic, and textural characteristics, are well-studied. As our exploration of the Solar System continues, so too does the inventory of intrusive and extrusive igneous rocks, settings, and processes. The results of planetary exploration have also clearly demonstrated that impact cratering is a ubiquitous geological process that has affected, and will continue to affect, all planetary objects with a solid surface, whether that be rock or ice. It is now recognized that the production of igneous rocks is a fundamental outcome of hypervelocity impact. The goal of this review is to provide an up-to-date synthesis of our knowledge and understanding of igneous rocks formed by hypervelocity impact. Following a brief overview of the basics of the impact process, we describe how and why melts are generated during impact events and how impact melting differs from endogenic igneous processes. While the process may differ, we show that the products of hypervelocity impact can share close similarities with volcanic and shallow intrusive igneous rocks of endogenic origin. Such impact melt rocks, as they are termed, can display lobate margins and cooling cracks, columnar joints and at the hand specimen and microscopic scale, such rocks can display mineral textures that are typical of volcanic rocks, such as quench crystallites, ophitic, porphyritic, as well as features such as vesicles, flow textures, and so on. Historically, these similarities led to the misidentification of some igneous rocks now known to be impact melt rocks as being of endogenic origin. This raises the question as to how to distinguish between an impact versus an endogenic origin for igneous-like rocks on other planetary bodies where fieldwork and sample analysis may not

  8. Remarks on some rock neutron parameters

    International Nuclear Information System (INIS)

    Czubek, J.A.

    1983-01-01

    A method to calculate the thermal neutron parameters (absorption cross-section, diffusion coefficient and diffusion length) of rocks is given. It is based on a proper energy averaging of cross-sections for all rock matrix and rock saturating liquid constituents. Special emphasis is given to the presence of hydrogen. The diffusion lengths in different lithologies in the function of the variable rock porosity have been calculated. An influence of the thermal neutron spectrum on the shape of the porosity calibration curves for the dual spacing neutron method is shown. This influence has been estimated on two porosity units, on average. (author)

  9. Sorption of radionuclides on hard rocks

    International Nuclear Information System (INIS)

    Berry, J.A.; Bourke, P.J.; Green, A.; Littleboy, A.K.

    1987-09-01

    Methods for measuring sorption on hard rocks, particularly of strontium, caesium, neptunium and americium on Darley Dale sandstone and Welsh slate have been investigated. The methods tried included batch tests with crushed rock and tests of simultaneous diffusion and convection with sorption on intact rock. High pressures (800m H 2 O) were used in the convective tests to pump water quickly through the rock samples and to measure high sorptivities in times shorter than those needed in the diffusive methods with intact samples. (author)

  10. Protein Kinase A in Cancer

    International Nuclear Information System (INIS)

    Caretta, Antonio; Mucignat-Caretta, Carla

    2011-01-01

    In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors

  11. Protein Kinase A in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Caretta, Antonio; Mucignat-Caretta, Carla, E-mail: carla.mucignat@unipd.it [Department of Human Anatomy and Physiology, University of Padova, Via Marzolo 3, 35131 Padova (Italy)

    2011-02-28

    In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors.

  12. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas

    2009-01-01

    of numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites......, the activation loop and the Z/TM in the C-terminal extension. We provide evidence that phosphorylation of the Z/TM site of PRK2 inhibits its interaction with PDK1. Our studies further provide a mechanistic model to explain different steps in the docking interaction and regulation. Interestingly, we found...... that the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2 and do...

  13. Isoprenoid biosynthesis and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Henneman, L.

    2011-01-01

    Mevalonaat Kinase Deficiëntie (MKD) is een aangeboren ziekte geassocieerd met heftige koortsaanvallen die drie tot vier dagen aanhouden en gepaard gaan met koude rillingen, gewrichtsklachten, huiduitslag, hoofdpijn, duizeligheid, buikpijn, braken en diarree. De koortsaanvallen treden gemiddeld eens

  14. Expression Profiling of Tyrosine Kinase Genes

    National Research Council Canada - National Science Library

    Weier, Heinz

    2000-01-01

    ... of these genes parallels the progression of tumors to a more malignant phenotype. We developed a DNA micro-array based screening system to monitor the level of expression of tyrosine kinase (tk...

  15. MAP kinase cascades in Arabidopsis innate immunity

    DEFF Research Database (Denmark)

    Rasmussen, Magnus Wohlfahrt; Roux, Milena Edna; Petersen, Morten

    2012-01-01

    Plant mitogen-activated protein kinase (MAPK) cascades generally transduce extracellular stimuli into cellular responses. These stimuli include the perception of pathogen-associated molecular patterns (PAMPs) by host transmembrane pattern recognition receptors which trigger MAPK-dependent innate ...

  16. Protein Kinases in Human Breast Carcinoma

    National Research Council Canada - National Science Library

    Cane, William

    1998-01-01

    .... Rak is a novel nuclear tyrosine that our group has identified in breast cancer tissues and cell lines that has structural homology to the Src tyrosine kinase, with SH2 and SH3 domains at its amino terminus...

  17. Hydrogeomechanics for rock engineering: coupling subsurface hydrogeomechanical assessement and hydrogeotechnical mapping on fracturated rock masses

    OpenAIRE

    Meirinhos, João Miguel de Freitas

    2015-01-01

    The present work aims to achieve and further develop a hydrogeomechanical approach in Caldas da Cavaca hydromineral system rock mass (Aguiar da Beira, NW Portugal), and contribute to a better understanding of the hydrogeological conceptual site model. A collection of several data, namely geology, hydrogeology, rock and soil geotechnics, borehole hydraulics and hydrogeomechanics, was retrieved from three rock slopes (Lagoa, Amores and Cancela). To accomplish a comprehensive analysis and rock e...

  18. Ror receptor tyrosine kinases: orphans no more

    OpenAIRE

    Green, Jennifer L.; Kuntz, Steven G.; Sternberg, Paul W.

    2008-01-01

    Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either act...

  19. Mediator kinase module and human tumorigenesis.

    Science.gov (United States)

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  20. Abiogenic methanogenesis in crystalline rocks

    Energy Technology Data Exchange (ETDEWEB)

    Lollar, B.S.; Frape, S.K. (Univ. of Waterloo, Ontario (Canada)); Weise, S.M. (Institut fuer Hydrologie (G.S.F), Neuherberg (Germany)); Fritz, P. (UFZ, Umweltforschungszentrum, Leipzig-Halle (Germany)); Macko, S.A. (Univ. of Virginia, Charlottesville, VA (United States)); Welhan, J.A. (Idaho State Univ., Pacatello, ID (United States))

    1993-12-01

    Isotopically anomalous CH[sub 4]-rich gas deposits are found in mining sites on both the Canadian and Fennoscandian shields. With [delta][sup 13]C[sub CH4] values from -22.4 to -48.5% and [delta]D[sub CH4] values from -133 to -372%, these methane deposits cannot be accounted for by conventional processes for bacterial or thermogenic methanogenesis. Compositionally the gases are similar to other CH[sub 4]-rich gas occurrences found in Canadian and Fennoscandian shield rocks. However, the isotopically anomalous gases of this study are characterized by unexpectedly high concentrations of H[sub 2] gas, ranging from several volume percent up to 30 vol%. The H[sub 2] gases are consistently depleted in the heavy isotope, with [delta]D[sub H[sub 2

  1. An investigation of rock fall and pore water pressure using LIDAR in Highway 63 rock cuts.

    Science.gov (United States)

    2014-07-01

    The purpose of this research work is compare LIDAR scanning measurements of rock fall with the natural changes in groundwater level to determining the effect of water pressures (levels) on rock fall. To collect the information of rock cut volume chan...

  2. Fibronectin phosphorylation by ecto-protein kinase

    International Nuclear Information System (INIS)

    Imada, Sumi; Sugiyama, Yayoi; Imada, Masaru

    1988-01-01

    The presence of membrane-associated, extracellular protein kinase (ecto-protein kinase) and its substrate proteins was examined with serum-free cultures of Swiss 3T3 fibroblast. When cells were incubated with [γ- 32 ]ATP for 10 min at 37 degree C, four proteins with apparent molecular weights between 150 and 220 kDa were prominently phosphorylated. These proteins were also radiolabeled by lactoperoxidase catalyzed iodination and were sensitive to mild tryptic digestion, suggesting that they localized on the cell surface or in the extracellular matrix. Phosphorylation of extracellular proteins with [γ- 32 P]ATP in intact cell culture is consistent with the existence of ecto-protein kinase. Anti-fibronectin antibody immunoprecipitated one of the phosphoproteins which comigrated with a monomer and a dimer form of fibronectin under reducing and nonreducing conditions of electrophoresis, respectively. The protein had affinity for gelatin as demonstrated by retention with gelatin-conjugated agarose. This protein substrate of ecto-protein kinase was thus concluded to be fibronectin. The sites of phosphorylation by ecto-protein kinase were compared with those of intracellularly phosphorylated fibronectin by the analysis of radiolabeled amino acids and peptides. Ecto-protein kinase phosphorylated fibronectin at serine and threonine residues which were distinct from the sites of intracellular fibronectin phosphorylation

  3. The PIM kinases in hematological cancers.

    Science.gov (United States)

    Alvarado, Yesid; Giles, Francis J; Swords, Ronan T

    2012-02-01

    The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.

  4. Computational Models of Rock Failure

    Science.gov (United States)

    May, Dave A.; Spiegelman, Marc

    2017-04-01

    Practitioners in computational geodynamics, as per many other branches of applied science, typically do not analyse the underlying PDE's being solved in order to establish the existence or uniqueness of solutions. Rather, such proofs are left to the mathematicians, and all too frequently these results lag far behind (in time) the applied research being conducted, are often unintelligible to the non-specialist, are buried in journals applied scientists simply do not read, or simply have not been proven. As practitioners, we are by definition pragmatic. Thus, rather than first analysing our PDE's, we first attempt to find approximate solutions by throwing all our computational methods and machinery at the given problem and hoping for the best. Typically this approach leads to a satisfactory outcome. Usually it is only if the numerical solutions "look odd" that we start delving deeper into the math. In this presentation I summarise our findings in relation to using pressure dependent (Drucker-Prager type) flow laws in a simplified model of continental extension in which the material is assumed to be an incompressible, highly viscous fluid. Such assumptions represent the current mainstream adopted in computational studies of mantle and lithosphere deformation within our community. In short, we conclude that for the parameter range of cohesion and friction angle relevant to studying rocks, the incompressibility constraint combined with a Drucker-Prager flow law can result in problems which have no solution. This is proven by a 1D analytic model and convincingly demonstrated by 2D numerical simulations. To date, we do not have a robust "fix" for this fundamental problem. The intent of this submission is to highlight the importance of simple analytic models, highlight some of the dangers / risks of interpreting numerical solutions without understanding the properties of the PDE we solved, and lastly to stimulate discussions to develop an improved computational model of

  5. Hydraulic conductivity of rock fractures

    International Nuclear Information System (INIS)

    Zimmerman, R.W.; Bodvarsson, G.S.

    1994-10-01

    Yucca Mountain, Nevada contains numerous geological units that are highly fractured. A clear understanding of the hydraulic conductivity of fractures has been identified as an important scientific problem that must be addressed during the site characterization process. The problem of the flow of a single-phase fluid through a rough-walled rock fracture is discussed within the context of rigorous fluid mechanics. The derivation of the cubic law is given as the solution to the Navier-Stokes equations for flow between smooth, parallel plates, the only fracture geometry that is amenable to exact treatment. The various geometric and kinetic conditions that are necessary in order for the Navier-Stokes equations to be replaced by the more tractable lubrication or Hele-Shaw equations are studied and quantified. Various analytical and numerical results are reviewed pertaining to the problem of relating the effective hydraulic aperture to the statistics of the aperture distribution. These studies all lead to the conclusion that the effective hydraulic aperture is always less than the mean aperture, by a factor that depends on the ratio of the mean value of the aperture to its standard deviation. The tortuosity effect caused by regions where the rock walls are in contact with each other is studied using the Hele-Shaw equations, leading to a simple correction factor that depends on the area fraction occupied by the contact regions. Finally, the predicted hydraulic apertures are compared to measured values for eight data sets from the literature for which aperture and conductivity data were available on the same fracture. It is found that reasonably accurate predictions of hydraulic conductivity can be made based solely on the first two moments of the aperture distribution function, and the proportion of contact area. 68 refs

  6. Radon exhalation from granitic rocks

    Energy Technology Data Exchange (ETDEWEB)

    Del Claro, Flávia; Paschuk, Sergei A.; Corrêa, Janine N.; Mazer, Wellington; Narloch, Danielle Cristine; Martin, Aline Cristina [Universidade Tecnológica Federal do Paraná (UTFPR), Curitiba, PR (Brazil); Denyak, Valeriy, E-mail: flaviadelclaro@gmail.com, E-mail: spaschuk@gmail.com, E-mail: janine_nicolosi@hotmail.com, E-mail: denyak@gmail.com [Instituto de Pesquisa Pelé Pequeno Príncipe (IPPP), Curitiba, PR (Brazil)

    2017-07-01

    Naturally occurring radionuclides such as radon ({sup 222}Rn), its decay products and other elements from the radioactive series of uranium ({sup 238}U and {sup 235}U) and thorium ({sup 232}Th) are an important source of human exposure to natural radioactivity. The worldwide evaluation of health radiobiological effects and risks from population exposure to natural radionuclides is a growing concern. About 50% of personal radiation annual dose is related to radionuclides such as radon ({sup 222}Rn), thoron ({sup 220}Rn), radium ({sup 226}Ra), thorium ({sup 232}Th) and potassium ({sup 40}K), which are present in modern materials commonly used in construction of dwellings and buildings. The radioactivity of marbles and granites is of big concern since under certain conditions the radioactivity levels of these materials can be hazardous to the population and require the implementation of mitigation procedures. Present survey of the {sup 222}Rn and {sup 220}Rn activity concentration liberated in the air was performed using commercialized Brazilian granite rocks at national market as well as exported to other countries. The {sup 222}Rn and {sup 220}Rn measurements were performed using the AlphaGUARD instant monitor and RAD7 detector, respectively. This study was performed at the Applied Nuclear Physics Laboratory of the Federal University of Technology – Paraná (UTFPR). Obtained results of radon concentration activity in air exhaled studied samples of granites varied from 3±1 Bq/m{sup 3} to 2087±19 Bq/m{sup 3}, which shows that some samples of granitic rocks represent rather elevated health risk the population. (author)

  7. Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall.

    Science.gov (United States)

    Araos, Patricio; Mondaca, David; Jalil, Jorge E; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz

    2016-12-01

    Diuretics are current antihypertensive drugs since they reduce blood pressure and cardiovascular risk. Increased vascular tone is modulated in a relevant way by the RhoA/Rho-kinase (ROCK) pathway, by acting on vascular smooth muscle cell contraction. This pathway has also proremodeling vascular effects. There are few data on the role of diuretics on both vascular ROCK activation and on proremodeling effects. We assessed the effects of hydrochlorothiazide (HCTZ) and spironolactone (spiro) alone and in combination with the ROCK inhibitor fasudil (FAS) on ROCK activation, gene expression of proremodeling markers and on hypertrophy in the aortic wall of hypertensive rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats (male, Sprague-Dawley) were randomized to the specific ROCK inhibitor FAS, HCTZ, spiro or the combinations of FAS/HCTZ or FAS/spiro for 3 weeks. At the end of the study, ROCK activation (by western blot), gene expression of proremodeling markers (by reverse transcription polymerase chain reaction, RT-PCR) and vascular hypertrophy (by morphometry) were determined in the aortic wall. All treatments significantly reduced blood pressure. In the DOCA rats the p-myosin phosphatase target protein-1 (MYPT1)/t-MYPT1 ratio, index of ROCK activation was higher by 2.8 fold (p diuretics alone or in combination with FAS. In the aortic wall, both HCTZ and spiro in antihypertensive doses reduce ROCK activation, subsequent expression of genes that promote vascular remodeling and hypertrophy in this experimental model of hypertension. These effects could explain some of their clinical benefits in hypertensive patients. © The Author(s), 2016.

  8. The History of Rock Art Research

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. The History of Rock Art Research. Rock art in South India was discovered as early as 1891.The earliest discovery of petroglyphs on the Koppagallu hill in Bellary district was made by Fred Fawcett (1892) who with the assistance of H.T.Knox and Robert Sewell ...

  9. Using Rock Music To Teach History.

    Science.gov (United States)

    Hoffman, Paul Dennis

    1985-01-01

    A secondary history teacher describes how he uses rock and roll music to help students study and interpret modern American history. Besides being a lot of fun to teach, a rock unit makes students realize that even contemporary music has a place in history. (RM)

  10. A guide for rock identification. 4. ed.

    International Nuclear Information System (INIS)

    Pape, H.

    1981-01-01

    The book is based on a practical course for students of geology, mineralogy, geography, and constructional engineering. It will also help interested laymen to identify rocks. Tables are presented which guide the reader in his analysis, so that he will quickly arrive at the name of a rock, the group to which it belongs, and some information on its characteristics and origin. (orig.) [de

  11. Rock Cycle. K-6 Science Curriculum.

    Science.gov (United States)

    Blueford, J. R.; And Others

    Rock Cycle is one of the units of a K-6 unified science curriculum program. The unit consists of four organizing sub-themes: (1) chemistry (introducing the topics of matter, elements, compounds, and chemical bonding); (2) characteristics (presenting hands-on activities with rocks and minerals); (3) minerals (emphasizing the aesthetic and economic…

  12. Phosphine from rocks: mechanically driven phosphate reduction?

    Science.gov (United States)

    Glindemann, Dietmar; Edwards, Marc; Morgenstern, Peter

    2005-11-01

    Natural rock and mineral samples released trace amounts of phosphine during dissolution in mineral acid. An order of magnitude more phosphine (average 1982 ng PH3 kg rock and maximum 6673 ng PH3/kg rock) is released from pulverized rock samples (basalt, gneiss, granite, clay, quartzitic pebbles, or marble). Phosphine was correlated to hardness and mechanical pulverization energy of the rocks. The yield of PH3 ranged from 0 to 0.01% of the total P content of the dissolved rock. Strong circumstantial evidence was gathered for reduction of phosphate in the rock via mechanochemical or "tribochemical" weathering at quartz and calcite/marble inclusions. Artificial reproduction of this mechanism by rubbing quartz rods coated with apatite-phosphate to the point of visible triboluminescence, led to detection of more than 70 000 ng/kg PH3 in the apatite. This reaction pathway may be considered a mechano-chemical analogue of phosphate reduction from lightning or electrical discharges and may contribute to phosphine production via tectonic forces and processing of rocks.

  13. Cenozoic volcanic rocks of Saudi Arabia

    Science.gov (United States)

    Coleman, R.G.; Gregory, R.T.; Brown, G.F.

    2016-01-01

    The Cenozoic volcanic rocks of Saudi Arabia cover about 90,000 km2, one of the largest areas of alkali olivine basalt in the world. These volcanic rocks are in 13 separate fields near the eastern coast of the Red Sea and in the western Arabian Peninsula highlands from Syria southward to the Yemen Arab Republic.

  14. Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival.

    Directory of Open Access Journals (Sweden)

    Daniel Thomas

    Full Text Available The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K, promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting

  15. Sorption of cesium in intact rock

    International Nuclear Information System (INIS)

    Puukko, E.

    2014-04-01

    The mass distribution coefficient K d is used in performance assessment (PA) to describe sorption of a radionuclide on rock. The R d is determined using crushed rock which causes uncertainty in converting the R d values to K d values for intact rock. This work describes a method to determine the equilibrium of sorption on intact rock. The rock types of the planned Olkiluoto waste disposal site were T-series mica gneiss (T-MGN), T-series tonalite granodiorite granite gneiss (T-TGG), P-series tonalite granodiorite granite gneiss (P-TGG) and pegmatitic granite (PGR). These rocks contain different amount of biotite which is the main sorbing mineral. The sorption of cesium on intact rock slices was studied by applying an electrical field to speed up migration of cesium into the rock. Cesium is in the solution as a noncomplex cation Cs + and it is sorbed by ion exchange. The tracer used in the experiments was 134 Cs. The experimental sorption on the intact rock is compared with values calculated using the in house cation exchange sorption model (HYRL model) in PHREEQC program. The observed sorption on T-MGN and T-TGG rocks was close to the calculated values. Two PGR samples were from a depth of 70 m and three samples were from a depth of 150 m. Cesium sorbed more than predicted on the two 70 m PGR samples. The sorption of Cs on the three 150 m PGR samples was small which was consistent with the calculations. The pegmatitic granite PGR has the smallest content of biotite of the four rock types. In the case of P-TGG rock the observed values of sorption were only half of the calculated values. Two kind of slices were cut from P-TGG drill core. The slices were against and to the direction of the foliation of the biotite rims. The sorption of cesium on P-TGG rock was same in both cases. The results indicated that there was no effect of the directions of the electric field and the foliation of biotite in the P-TGG rock. (orig.)

  16. Finding the right rocks on Mars

    Science.gov (United States)

    Hargraves, R. B.; Knudsen, J. M.; Madsen, M. B.; Bertelsen, P.

    Locating a rock on the surface of Mars that bears unambiguous evidence of the existence—prior or present—of life on that planet is, understandably, the “Holy Grail” of NASAs sample return missions. Remote recognition of such a rock on Mars will not be easy. We do know, however, that present in the Martian crust—especially in the “Southern highlands”—is rock carrying strong natural remanent magnetization (NRM). Characterization of such magnetized rock has profound implications for adding to our knowledge about the origin and early evolution of the Martian interior, lithosphere, atmosphere, and possibly even Martian life forms [Ward and Brownlee, 2000]. Moreover, it should be possible to recognize such rocks by use of a simple magnetic compass mounted on a Rover.

  17. First Grinding of a Rock on Mars

    Science.gov (United States)

    2004-01-01

    The round, shallow depression in this image resulted from history's first grinding of a rock on Mars. The rock abrasion tool on NASA's Spirit rover ground off the surface of a patch 45.5 millimeters (1.8 inches) in diameter on a rock called Adirondack during Spirit's 34th sol on Mars, Feb. 6, 2004. The hole is 2.65 millimeters (0.1 inch) deep, exposing fresh interior material of the rock for close inspection with the rover's microscopic imager and two spectrometers on the robotic arm. This image was taken by Spirit's panoramic camera, providing a quick visual check of the success of the grinding. The rock abrasion tools on both Mars Exploration Rovers were supplied by Honeybee Robotics, New York, N.Y.

  18. Disc cutter wear and rock texture in hard rock TBM tunneling

    International Nuclear Information System (INIS)

    Koizumi, Yu; Tsusaka, Kimikazu; Tanimoto, Chikaosa; Nakagawa, Shigeo; Fujita, Naoya

    2008-01-01

    Disc cutter wear in TBM tunneling is caused by initial fragmentation of a solid rock face (the primary fragmentation) and fragmentation of residual rock pieces between a cutterhead and the face (the secondary fragmentation). In two projects through sedimentary and granitic rocks, the authors investigated the relationships between the rate of cutter wear caused by the primary fragmentation, point load index and the grain size and contents of abrasive minerals. As a result, it was found that the tensile strength and the mineral contents of rocks significantly influenced the cutter wear in both projects and thus it is necessary to take into account of rock type. (author)

  19. Fragment Size Distribution of Blasted Rock Mass

    Science.gov (United States)

    Jug, Jasmin; Strelec, Stjepan; Gazdek, Mario; Kavur, Boris

    2017-12-01

    Rock mass is a heterogeneous material, and the heterogeneity of rock causes sizes distribution of fragmented rocks in blasting. Prediction of blasted rock mass fragmentation has a significant role in the overall economics of opencast mines. Blasting as primary fragmentation can significantly decrease the cost of loading, transport, crushing and milling operations. Blast fragmentation chiefly depends on the specific blast design (geometry of blast holes drilling, the quantity and class of explosive, the blasting form, the timing and partition, etc.) and on the properties of the rock mass (including the uniaxial compressive strength, the rock mass elastic Young modulus, the rock discontinuity characteristics and the rock density). Prediction and processing of blasting results researchers can accomplish by a variety of existing software’s and models, one of them is the Kuz-Ram model, which is possibly the most widely used approach to estimating fragmentation from blasting. This paper shows the estimation of fragmentation using the "SB" program, which was created by the authors. Mentioned program includes the Kuz-Ram model. Models of fragmentation are confirmed and calibrated by comparing the estimated fragmentation with actual post-blast fragmentation from image processing techniques. In this study, the Kuz-Ram fragmentation model has been used for an open-pit limestone quarry in Dalmatia, southern Croatia. The resulting calibrated value of the rock factor enables the quality prognosis of fragmentation in further blasting works, with changed drilling geometry and blast design parameters. It also facilitates simulation in the program to optimize blasting works and get the desired fragmentations of the blasted rock mass.

  20. Permanganate diffusion and reaction in sedimentary rocks.

    Science.gov (United States)

    Huang, Qiuyuan; Dong, Hailiang; Towne, Rachael M; Fischer, Timothy B; Schaefer, Charles E

    2014-04-01

    In situ chemical oxidation using permanganate has frequently been used to treat chlorinated solvents in fractured bedrock aquifers. However, in systems where matrix back-diffusion is an important process, the ability of the oxidant to migrate and treat target contaminants within the rock matrix will likely determine the overall effectiveness of this remedial approach. In this study, a series of diffusion experiments were performed to measure the permanganate diffusion and reaction in four different types of sedimentary rocks (dark gray mudstone, light gray mudstone, red sandstone, and tan sandstone). Results showed that, within the experimental time frame (~2 months), oxidant migration into the rock was limited to distances less than 500 μm. The observed diffusivities for permanganate into the rock matrices ranged from 5.3 × 10(-13) to 1.3 × 10(-11) cm(2)/s. These values were reasonably predicted by accounting for both the rock oxidant demand and the effective diffusivity of the rock. Various Mn minerals formed as surface coatings from reduction of permanganate coupled with oxidation of total organic carbon (TOC), and the nature of the formed Mn minerals was dependent upon the rock type. Post-treatment tracer testing showed that these Mn mineral coatings had a negligible impact on diffusion through the rock. Overall, our results showed that the extent of permanganate diffusion and reaction depended on rock properties, including porosity, mineralogy, and organic carbon. These results have important implications for our understanding of long-term organic contaminant remediation in sedimentary rocks using permanganate. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Measurements of thermal properties of rocks

    International Nuclear Information System (INIS)

    Kumada, Toshiaki

    2001-02-01

    The report concerns the measurement of thermal conductivity and specific heat of supplied sedimental rock B and Funyu rock. The method of measurement of these properties was done with the method which was developed at 1997 and improved much in its accuracy by the present author et al. The porosity of sedimental rock B is 0.55, which is deduced from the density of rock (the porosity deduced from the difference between dry and water filled conditions is 0.42) and the shape and size of pores in rock are much different. Its thermal conductivity is 0.238 W/mK in dry and 1.152 W/mK in water filled conditions respectively, while the thermal conductivity of bentonite is 0.238 W/mK in dry and 1.152 W/mK in water saturated conditions. The difference of thermal conductivity between dry and water saturated conditions is little difference in sedimental rock B and bentonite at same porosity. The porosity of Funyu rock is 0.26 and the shape and size of pores in the rock are uniform. Its thermal conductivity is 0.914 W/mK in dry and 1.405 W/mK in water saturated conditions, while the thermal conductivity of bentonite is 0.606 W/mK in dry and 1.591 W/mK in water saturated conditions respectively. The correlation estimating thermal conductivity of rocks was derived based on Fricke correlation by presuming rocks as a suspension. (author)

  2. The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing.

    Science.gov (United States)

    Hannemann, Sebastian; Madrid, Ricardo; Stastna, Jana; Kitzing, Thomas; Gasteier, Judith; Schönichen, André; Bouchet, Jerome; Jimenez, Alberto; Geyer, Matthias; Grosse, Robert; Benichou, Serge; Fackler, Oliver T

    2008-10-10

    Diaphanous-related formins (DRFs) mediate GTPase-triggered actin rearrangements to regulate central cellular processes, such as cell motility and cytokinesis. The DRF FHOD1 interacts with the Rho-GTPase Rac1 and mediates formation of actin stress fibers in its deregulated form; the physiologically relevant activities and molecular mechanisms of endogenous FHOD1, however, are still unknown. Here we report that FHOD1 physically associates via the N-terminal part of its FH2 domain with the central domain of ROCK1. Although FHOD1 does not affect the kinase activity of ROCK1, the DRF is an efficient substrate for phosphorylation by ROCK1. Co-expression of FHOD1 and ROCK1 results in the generation of nonapoptotic plasma membrane (PM) blebs, to which the DRF is efficiently recruited. Blebbing induced by FHOD1 and ROCK1 depends on F-actin integrity, the Rho-ROCK cascade, and Src activity and is reminiscent of the recently described PM blebs triggered by expression of Src homology 4 (SH4) domain PM targeting signals. Consistently, endogenous FHOD1 is required in SH4 domain expressing cells for efficient PM blebbing and rounded cell morphology in two-dimensional cultures or three-dimensional matrices, respectively. Efficient association of FHOD1 with ROCK1, as well as recruitment of the DRF to blebs, depends on Src activity, suggesting that the functional interaction between both proteins is regulated by Src. These results define a role for endogenous FHOD1 in SH4 domain-induced blebbing and suggest that its activity is regulated by ROCK1 in a Src-dependent manner.

  3. Non-degradative Ubiquitination of Protein Kinases.

    Directory of Open Access Journals (Sweden)

    K Aurelia Ball

    2016-06-01

    Full Text Available Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well.

  4. Crystal structure of Cryptosporidium parvum pyruvate kinase.

    Directory of Open Access Journals (Sweden)

    William J Cook

    Full Text Available Pyruvate kinase plays a critical role in cellular metabolism of glucose by serving as a major regulator of glycolysis. This tetrameric enzyme is allosterically regulated by different effector molecules, mainly phosphosugars. In response to binding of effector molecules and substrates, significant structural changes have been identified in various pyruvate kinase structures. Pyruvate kinase of Cryptosporidium parvum is exceptional among known enzymes of protozoan origin in that it exhibits no allosteric property in the presence of commonly known effector molecules. The crystal structure of pyruvate kinase from C. parvum has been solved by molecular replacement techniques and refined to 2.5 Å resolution. In the active site a glycerol molecule is located near the γ-phosphate site of ATP, and the protein structure displays a partially closed active site. However, unlike other structures where the active site is closed, the α6' helix in C. parvum pyruvate kinase unwinds and assumes an extended conformation. In the crystal structure a sulfate ion is found at a site that is occupied by a phosphate of the effector molecule in many pyruvate kinase structures. A new feature of the C. parvum pyruvate kinase structure is the presence of a disulfide bond cross-linking the two monomers in the asymmetric unit. The disulfide bond is formed between cysteine residue 26 in the short N-helix of one monomer with cysteine residue 312 in a long helix (residues 303-320 of the second monomer at the interface of these monomers. Both cysteine residues are unique to C. parvum, and the disulfide bond remained intact in a reduced environment. However, the significance of this bond, if any, remains unknown at this time.

  5. A systematic evaluation of protein kinase a-a-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P|info:eu-repo/dai/nl/341566551; van der Heyden, Marcel A G; Kok, Bart; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Scholten, Arjen|info:eu-repo/dai/nl/313939780

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  6. A systematic evaluation of protein kinase A-A-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P; van der Heyden, MAG; Kok, Bart; Heck, Albert J R; Scholten, Arjen

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  7. Role of adiponectin/phosphatidylinositol 3-kinase/protein kinase B ...

    African Journals Online (AJOL)

    The adiponectin/phosphatidylinositol 3-kinase/protein kinase B (ADP/PI3k/Akt) signal transduction pathway has an important role in promoting cell survival. This study was designed to determine if the ADP/PI3K/Akt signaling pathway has a role in the mechanism of ischemia–reperfusion injury in vivo. Sprague–Dawley rats ...

  8. Phosphorylation of nm23/nucleoside diphosphate kinase by casein kinase 2 in vitro

    DEFF Research Database (Denmark)

    Engel, M; Issinger, O G; Lascu, I

    1994-01-01

    We have investigated phosphorylation of human nucleoside diphosphate kinase (NDPK) and of homologous NDPK from different species by human casein kinase 2 (CK-2). The human NDPK isotypes A and B were phosphorylated by CK-2 in vitro both when the purified proteins and total lysate of HL-60 leukemia...

  9. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Ting-Lei Gu

    Full Text Available Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23 of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted.

  10. The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

    Science.gov (United States)

    Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

    2014-11-01

    The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

  11. The Link between Protein Kinase CK2 and Atypical Kinase Rio1

    Directory of Open Access Journals (Sweden)

    Konrad Kubiński

    2017-02-01

    Full Text Available The atypical kinase Rio1 is widespread in many organisms, ranging from Archaebacteria to humans, and is an essential factor in ribosome biogenesis. Little is known about the protein substrates of the enzyme and small-molecule inhibitors of the kinase. Protein kinase CK2 was the first interaction partner of Rio1, identified in yeast cells. The enzyme from various sources undergoes CK2-mediated phosphorylation at several sites and this modification regulates the activity of Rio1. The aim of this review is to present studies of the relationship between the two different kinases, with respect to CK2-mediated phosphorylation of Rio1, regulation of Rio1 activity, and similar susceptibility of the kinases to benzimidazole inhibitors.

  12. syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

    Science.gov (United States)

    El-Hillal, O.; Kurosaki, T.; Yamamura, H.; Kinet, J.-P.; Scharenberg, A. M.

    1997-01-01

    Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well. PMID:9050880

  13. Mechanism of polyphosphate kinase from Propionibacterium shermanii

    International Nuclear Information System (INIS)

    Robinson, N.A.

    1986-01-01

    Polyphosphate kinase, which catalyzes the reaction shown below, is one of two enzymes which have been reported to catalyze the synthesis of polyphosphate. Purification performed by ammonium sulfate precipitation (0-40% fraction) was followed by chromatography. The enzyme represents 70% of the protein in the hydroxylapatite pool and is stable at this level of purity. The subunit molecular weight was determined by SDS polyacrylamide gel analysis, (83,000 +/- 3000), nondenaturing polyacrylamide gel electrophoresis, (80,000 and 86,000 daltons), gel filtration (Biogel A 0.5m column was 85,000 +/- 4000.) Polyphosphate kinase appears to be a monomeric enzyme of ∼83,000 daltons. Four assays were developed for polyphosphate kinase. Basic proteins such as polylysine stimulate the synthesis of polyphosphate, these proteins cause precipitation of polyphosphate kinase from relatively impure enzyme extracts: Synthesized polyphosphate interacts noncovalently with the basic protein-enzyme precipitate. Efficient synthesis of polyphosphate requires the addition of either phosphate or short chain polyphosphate. Synthesis did occur at 1/10 the rate when neither of these two compounds were included. Initiation, elongation, and termination events of polyphosphate synthesis were examined. Short chain polyphosphate acts as a primer, with [ 32 P] short-chain polyphosphate incorporation into long chain polyphosphate by the kinase

  14. Radioimmunoassay of bovine heart protein kinase

    International Nuclear Information System (INIS)

    Fleischer, N.; Rosen, O.M.; Reichlin, M.

    1976-01-01

    Immunization of guinea pigs with bovine cardiac cAMP-dependent protein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) resulted in the development of precipitating antibodies to the cAMP-binding subunit of the enzyme. Both the phosphorylated and nonphosphorylated cAMP-binding protein of the protein kinase reacted with the antiserum. A radioimmunoassay was developed that detects 10 ng of holoenzyme and permits measurement of enzyme concentrations in bovine cardiac muscle. Bovine liver, kidney, brain, and skeletal muscle contain protein kinases which are immunologically identical to those found in bovine cardiac muscle. However, the proportion of immunoreactive enzyme activity differed for each tissue. All of the immunologically nonreactive enzyme in skeletal muscle and heart was separable from immunoreactive enzyme by chromatography on DEAE-cellulose. Rat tissues and pig heart contained protein kinase activity that cross reacted immunologically in a nonparallel fashion with bovine cardiac enzyme. These results indicate that cAMP-dependent protein kinases within and between species are immunologically heterogeneous

  15. The target landscape of clinical kinase drugs.

    Science.gov (United States)

    Klaeger, Susan; Heinzlmeir, Stephanie; Wilhelm, Mathias; Polzer, Harald; Vick, Binje; Koenig, Paul-Albert; Reinecke, Maria; Ruprecht, Benjamin; Petzoldt, Svenja; Meng, Chen; Zecha, Jana; Reiter, Katrin; Qiao, Huichao; Helm, Dominic; Koch, Heiner; Schoof, Melanie; Canevari, Giulia; Casale, Elena; Depaolini, Stefania Re; Feuchtinger, Annette; Wu, Zhixiang; Schmidt, Tobias; Rueckert, Lars; Becker, Wilhelm; Huenges, Jan; Garz, Anne-Kathrin; Gohlke, Bjoern-Oliver; Zolg, Daniel Paul; Kayser, Gian; Vooder, Tonu; Preissner, Robert; Hahne, Hannes; Tõnisson, Neeme; Kramer, Karl; Götze, Katharina; Bassermann, Florian; Schlegl, Judith; Ehrlich, Hans-Christian; Aiche, Stephan; Walch, Axel; Greif, Philipp A; Schneider, Sabine; Felder, Eduard Rudolf; Ruland, Juergen; Médard, Guillaume; Jeremias, Irmela; Spiekermann, Karsten; Kuster, Bernhard

    2017-12-01

    Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  16. Janus kinase inhibitors: jackpot or potluck?

    Directory of Open Access Journals (Sweden)

    Pavithran Keechilat

    2012-06-01

    Full Text Available The reports of a unique mutation in the Janus kinase-2 gene (JAK2 in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN: primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

  17. Rock stars for the day

    CERN Multimedia

    Stefania Pandolfi

    2015-01-01

    After a two-year hiatus, the CERN Hardronic Festival is back! On 8 August, ten CERN MusiClub bands will take to the stage for the popular event. As usual, the non-stop show will take place on the terrace of Restaurant 3 and will run until after midnight.   The Canettes Blues Band, part of the CERN MusiClub, performing live on the Music In The Park stage at the Montreux Jazz Festival, on 18 July 2013. A large range of musical styles will entertain the audience: from Irish folk, via 70s/80s/90s rock, to pop, blues and R&B. Alongside the music there will be activities for kids and food and drink stands. This year, the income from food sales will be donated to charity. The spirit that has characterised the festival ever since the first event in 1989 is that of a staff party. Any band who volunteers to play also helps to organise the event and set up the stage. “This is a really good thing because a festival that has been growing for many years requires a considerable amount of har...

  18. Tracer transport in fractured rocks

    International Nuclear Information System (INIS)

    Tsang, C.F.; Tsang, Y.W.; Hale, F.V.

    1988-07-01

    Recent interest in the safety of toxic waste underground disposal and nuclear waste geologic repositories has motivated many studies of tracer transport in fractured media. Fractures occur in most geologic formations and introduce a high degree of heterogeneity. Within each fracture, the aperture is not constant in value but strongly varying. Thus for such media, tracer tends to flow through preferred flowpaths or channels within the fractures. Along each of these channels, the aperture is also strongly varying. A detailed analysis is carried out on a 2D single fracture with variable apertures and the flow through channels is demonstrated. The channels defined this way are not rigidly set pathways for tracer transport, but are the preferred flow paths in the sense of stream-tubes in the potential theory. It is shown that such variable-aperture channels can be characterized by an aperture probability distribution function, and not by the exact deterministic geometric locations. We also demonstrate that the 2D tracer transport in a fracture can be calculated by a model of a system of 1D channels characterized by this distribution function only. Due to the channeling character of tracer transport in fractured rock, random point measurements of tracer breakthrough curves may give results with a wide spread in value due to statistical fluctuations. The present paper suggests that such a wide spread can probably be greatly reduced by making line/areal (or multiple) measurements covering a few spatial correlation lengths. 13 refs., 11 figs., 1 tab

  19. Rock cavern storage of spent fuel

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Won Jin; Kim, Kyung Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kwon, Sang Ki [Inha University, Incheon (Korea, Republic of)

    2015-12-15

    The rock cavern storage for spent fuel has been assessed to apply in Korea with reviewing the state of the art of the technologies for surface storage and rock cavern storage of spent fuel. The technical feasibility and economic aspects of the rock cavern storage of spent fuel were also analyzed. A considerable area of flat land isolated from the exterior are needed to meet the requirement for the site of the surface storage facilities. It may, however, not be easy to secure such areas in the mountainous region of Korea. Instead, the spent fuel storage facilities constructed in the rock cavern moderate their demands for the suitable site. As a result, the rock cavern storage is a promising alternative for the storage of spent fuel in the aspect of natural and social environments. The rock cavern storage of spent fuel has several advantages compared with the surface storage, and there is no significant difference on the viewpoint of economy between the two alternatives. In addition, no great technical difficulties are present to apply the rock cavern storage technologies to the storage of domestic spent fuel.

  20. Heating effects in Rio Blanco rock

    International Nuclear Information System (INIS)

    Taylor, R.W.; Bowen, D.W.; Rossler, P.E.

    1975-01-01

    Samples of ''sandstone'' from near the site of the upper Rio Blanco nuclear explosion were heated in the laboratory at temperatures between 600 and 900 0 C. The composition and amount of noncondensable (dry) gas released were measured and compared to the amount and composition of gas found underground following the explosion. The gas released from the rock heated in the laboratory contained approximately 80 percent CO 2 and 10 percent H 2 ; the balance was CO and CH 4 . With increasing temperature, the amounts of CO 2 , CO, and H 2 released increased. The composition of gas released by heating Rio Blanco rock in the laboratory is similar to the composition of gas found after the nuclear explosion except that it contains less natural gas (CH 4 , C 2 H 6 . . .). The amount of noncondensable gas released by heating the rock increases from approximately 0.1 mole/kg of rock at 600 0 C to 0.9 mole/kg at 900 0 C. Over 90 percent of the volatile components of the rock are released in less than 10 h at 900 0 C. A comparison of the amount of gas released by heating rock in the laboratory to the amount of gas released by the heat of the Rio Blanco nuclear explosion suggests that the explosion released the volatile material from about 0.42 mg of rock per joule of explosive energy (1700 to 1800 tonnes per kt). (auth)

  1. Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats.

    Science.gov (United States)

    Inan, Salim Yalcin; Soner, Burak Cem; Sahin, Ayse Saide

    2015-03-03

    Depression is one of the most common psychiatric disorders in the world; however, its mechanisms remain unclear. Recently, a new signal-transduction pathway, namely Rho/Rho-kinase signalling, has been suggested to be involved in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However there is no evidence showing the involvement of Rho-kinase pathway in depression. In addition, the infralimbic cortex, rodent equivalent to subgenual cingulate cortex has been shown to be responsible for emotional responses. Thus, in the present study, intracranial guide cannulae were stereotaxically implanted bilaterally into the infralimbic cortex, and the effects of repeated microinjections of a Rho-kinase (ROCK) inhibitor Y-27632 (10 nmol) were investigated in rats. Y-27632 significantly decreased immobility time and increased swimming and climbing behaviors when compared to fluoxetine (10 μg) and saline groups in the forced swim test. In addition, Y-27632 treatment did not affect spontaneous locomotor activity and forelimb use in the open-field and cylinder tests respectively; but it enhanced limb placing accuracy in the ladder rung walking test. Our results suggest that Y-27632 could be a potentially active antidepressant agent. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Protocols for the Design of Kinase-focused Compound Libraries.

    Science.gov (United States)

    Jacoby, Edgar; Wroblowski, Berthold; Buyck, Christophe; Neefs, Jean-Marc; Meyer, Christophe; Cummings, Maxwell D; van Vlijmen, Herman

    2018-05-01

    Protocols for the design of kinase-focused compound libraries are presented. Kinase-focused compound libraries can be differentiated based on the design goal. Depending on whether the library should be a discovery library specific for one particular kinase, a general discovery library for multiple distinct kinase projects, or even phenotypic screening, there exists today a variety of in silico methods to design candidate compound libraries. We address the following scenarios: 1) Datamining of SAR databases and kinase focused vendor catalogues; 2) Predictions and virtual screening; 3) Structure-based design of combinatorial kinase inhibitors; 4) Design of covalent kinase inhibitors; 5) Design of macrocyclic kinase inhibitors; and 6) Design of allosteric kinase inhibitors and activators. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Discussion on the origin of sedimentary rock resistivity

    International Nuclear Information System (INIS)

    Dong Gangjian

    2012-01-01

    Conduction current way of sedimentary rock sedimentary rock is caused by the internal structure of sedimentary rock sedimentary rock pore resistance depends on the salinity of pore water and clay content and distribution. Resistivity of sedimentary rock sedimentary rock major factor in mineral composition, water resistance, oil resistance. and sedimentary structures. In practice, we should give full attention to the difference between lithology and physical properties. (author)

  4. Phosphatidylinositol 3-Kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: importance of the morpholine ring

    Czech Academy of Sciences Publication Activity Database

    Andrs, M.; Kobarecny, J.; Jun, D.; Hodný, Zdeněk; Bartek, Jiří; Kuca, K.

    2015-01-01

    Roč. 58, č. 1 (2015), s. 41-71 ISSN 0022-2623 R&D Projects: GA MŠk(CZ) CZ.1.07/2.3.00/30.0044 Grant - others:University Hospital Hradec Kralove(CZ) 00179906; Faculty of Military Health Sciences, University of Defence(CZ) SV/FVZ201402 Institutional support: RVO:68378050 Keywords : DEPENDENT PROTEIN-KINASE * STRAND BREAK REPAIR * SELECTIVE PI3K-BETA INHIBITORS * TELANGIECTASIA MUTATED KINASE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.589, year: 2015

  5. The Usability of Rock-Like Materials for Numerical Studies on Rocks

    Science.gov (United States)

    Zengin, Enes; Abiddin Erguler, Zeynal

    2017-04-01

    The approaches of synthetic rock material and mass are widely used by many researchers for understanding the failure behavior of different rocks. In order to model the failure behavior of rock material, researchers take advantageous of different techniques and software. But, the majority of all these instruments are based on distinct element method (DEM). For modeling the failure behavior of rocks, and so to create a fundamental synthetic rock material model, it is required to perform related laboratory experiments for providing strength parameters. In modelling studies, model calibration processes are performed by using parameters of intact rocks such as porosity, grain size, modulus of elasticity and Poisson ratio. In some cases, it can be difficult or even impossible to acquire representative rock samples for laboratory experiments from heavily jointed rock masses and vuggy rocks. Considering this limitation, in this study, it was aimed to investigate the applicability of rock-like material (e.g. concrete) to understand and model the failure behavior of rock materials having complex inherent structures. For this purpose, concrete samples having a mixture of %65 cement dust and %35 water were utilized. Accordingly, intact concrete samples representing rocks were prepared in laboratory conditions and their physical properties such as porosity, pore size and density etc. were determined. In addition, to acquire the mechanical parameters of concrete samples, uniaxial compressive strength (UCS) tests were also performed by simultaneously measuring strain during testing. The measured physical and mechanical properties of these extracted concrete samples were used to create synthetic material and then uniaxial compressive tests were modeled and performed by using two dimensional discontinuum program known as Particle Flow Code (PFC2D). After modeling studies in PFC2D, approximately similar failure mechanism and testing results were achieved from both experimental and

  6. Look! It's Rock'n'roll!

    DEFF Research Database (Denmark)

    Lindelof, Anja

    2007-01-01

    , and dates. Consult your library or click here for more information on citing sources. -------------------------------------------------------------------------------- Anja Mølle Lindelof. (2007). Look! it's rock'n'roll! how television participated in shaping the visual genre conventions of popular music...... to personal names, capitalization, and dates. Consult your library or click here for more information on citing sources. -------------------------------------------------------------------------------- Anja Mølle Lindelof. "Look! It's Rock'n'roll! How television participated in shaping the visual genre....... Pay special attention to personal names, capitalization, and dates. Consult your library or click here for more information on citing sources. -------------------------------------------------------------------------------- TY - JOUR T1 - Look! It's Rock'n'roll! How television participated in shaping...

  7. Permeability Evolution and Rock Brittle Failure

    OpenAIRE

    Sun Qiang; Xue Lei; Zhu Shuyun

    2015-01-01

    This paper reports an experimental study of the evolution of permeability during rock brittle failure and a theoretical analysis of rock critical stress level. It is assumed that the rock is a strain-softening medium whose strength can be described by Weibull’s distribution. Based on the two-dimensional renormalization group theory, it is found that the stress level λ c (the ratio of the stress at the critical point to the peak stress) depends mainly on the homogeneity index or shape paramete...

  8. Deep fracturation of granitic rock mass

    International Nuclear Information System (INIS)

    Bles, J.L.; Blanchin, R.; Bonijoly, D.; Dutartre, P.; Feybesse, J.L.; Gros, Y.; Landry, J.; Martin, P.

    1986-01-01

    This documentary study realized with the financial support of the European Communities and the CEA aims at the utilization of available data for the understanding of the evolution of natural fractures in granitic rocks from the surface to deep underground, in various feasibility studies dealing with radioactive wastes disposal. The Mont Blanc road tunnel, the EDF Arc-Isere gallerie, the Auriat deep borehole and the Pyrenean rock mass of Bassies are studied. In this study are more particularly analyzed the relationship between small fractures and large faults, evolution with depth of fracture density and direction, consequences of rock decompression and relationship between fracturation and groundwater [fr

  9. Radon and rock bursts in deep mines

    International Nuclear Information System (INIS)

    Bulashevich, Yu.P.; Utkin, V.I.; Yurkov, A.K.; Nikolaev, V.V.

    1996-01-01

    Variation fields of radon concentration in time to ascertain stress-strain state of the North Ural bauxite mines have been studied. It is shown that dynamic changes in the stress-strain state of the rocks prior to the rock burst bring about variations in radon concentration in the observation wells. Depending on mutual positioning of the observation points and the rock burst epicenter, the above-mentioned variations differ in principle, reduction of radon concentration in the near zone and its increase in the far zone are observed [ru

  10. Laboratory measurements of rock thermal properties

    DEFF Research Database (Denmark)

    Bording, Thue Sylvester; Balling, N.; Nielsen, S.B.

    The thermal properties of rocks are key elements in understanding and modelling the temperature field of the subsurface. Thermal conductivity and thermal diffusivity can be measured in the laboratory if rock samples can be provided. We have introduced improvements to the divided bar and needle...... probe methods to be able to measure both thermal conductivity and thermal diffusivity. The improvements we implement include, for both methods, a combination of fast numerical finite element forward modelling and a Markov Chain Monte Carlo inversion scheme for estimating rock thermal parameters...

  11. Acoustics in rock and pop music halls

    DEFF Research Database (Denmark)

    Larsen, Niels Werner; Thompson, Eric Robert; Gade, Anders Christian

    2007-01-01

    The existing body of literature regarding the acoustic design of concert halls has focused almost exclusively on classical music, although there are many more performances of rhythmic music, including rock and pop. Objective measurements were made of the acoustics of twenty rock music venues...... in Denmark and a questionnaire was used in a subjective assessment of those venues with professional rock musicians and sound engineers. Correlations between the objective and subjective results lead, among others, to a recommendation for reverberation time as a function of hall volume. Since the bass...

  12. Lead isotopes in archaean plutonic rocks

    International Nuclear Information System (INIS)

    Oversby, V.M.

    1978-01-01

    Archaean intrusive rocks have initial Pb isotopic compositions which show a varied and complex history for the source regions of the rocks. Even the oldest rocks from Greenland indicate heterogenous U and Pb distribution prior to 3800 m.y. ago. Source regions with μ values less than 7 must have played a significant role in the early history of the earth. By late Archaean time U/Pb ratios of source regions had increased substantially. Data from Australia and North America show distinct regional differences, both within and between continents. (Auth.)

  13. Heat production / host rock compatibility; Waermeentwicklung / Gesteinsvertraeglichkeit

    Energy Technology Data Exchange (ETDEWEB)

    Meleshyn, A.; Weyand, T.; Bracke, G.; Kull, H.; Wieczorek, K.

    2016-05-15

    For the final high-level radioactive waste repository potential host rock formations are either rock salt or clays (Kristallin). Heat generating waste (decay heat of the radioactive materials) can be absorbed by the host rock. The effect of temperature increase on the thermal conductivity, the thermal expansion and the mechanical properties of salt, Kristallin, clays and argilliferous geotechnical barriers are described. Further issues of the report are the mineralogical behavior, phase transformations, hydrochemistry, microbial processes, gas formation, thermochemical processes and gas ingress. Recommendations for further research are summarized.

  14. Rapid formation of rock armour for soil - rock fragment mixture during simulated rainfall

    Science.gov (United States)

    Poultney, E.; McGrath, G. S.; Hinz, C.

    2009-04-01

    Preventing erosion is an important issue in disturbed semi-arid and arid landscapes. This is in particular of highest importance for mining companies while undertaking land rehabilitation. An onsite investigation of the impact of surface rock fragments on erosion was conducted at Telfer goldmine in the Great Sandy Desert, Western Australia. The study site is a waste rock dump designed to mimic the concave slope of a natural mesa to both discourage erosion and blend in with its natural surroundings. Four treatments were used to construct the slope: two are topsoil mixed with rock fragments, and two are unmixed topsoil. A field study investigating erosion rills, particle size distribution, rock fragment coverage surface roughness and vegetation was carried out to determine changes down and across slope. The treatments constructed by mixing topsoil and rock fragments are more stable and show rock fragment distributions that more closely resemble patterns found on natural mesas surrounding Telfer. A controlled study using trays of topsoil mixed with rock fragment volumes of 50%, 60%, 70% and 80% were used to investigate how varying mixtures of rock fragments and topsoil erode using rainfall intensities between 20 and 100 mm h-1. Two runs of 25 minutes each were used to assess the temporal evolution of rock armouring. Surface coverage results converged for the 50%, 60% and 70% mixtures after the first run to coverage of about 90%, suggesting that fine sediment proportion does not affect rate and degree of rock armouring.

  15. Sliding rocks on Racetrack Playa, Death Valley National Park: first observation of rocks in motion.

    Directory of Open Access Journals (Sweden)

    Richard D Norris

    Full Text Available The engraved trails of rocks on the nearly flat, dry mud surface of Racetrack Playa, Death Valley National Park, have excited speculation about the movement mechanism since the 1940s. Rock movement has been variously attributed to high winds, liquid water, ice, or ice flotation, but has not been previously observed in action. We recorded the first direct scientific observation of rock movements using GPS-instrumented rocks and photography, in conjunction with a weather station and time-lapse cameras. The largest observed rock movement involved > 60 rocks on December 20, 2013 and some instrumented rocks moved up to 224 m between December 2013 and January 2014 in multiple move events. In contrast with previous hypotheses of powerful winds or thick ice floating rocks off the playa surface, the process of rock movement that we have observed occurs when the thin, 3 to 6 mm, "windowpane" ice sheet covering the playa pool begins to melt in late morning sun and breaks up under light winds of -4-5 m/s. Floating ice panels 10 s of meters in size push multiple rocks at low speeds of 2-5 m/min. along trajectories determined by the direction and velocity of the wind as well as that of the water flowing under the ice.

  16. Effects of confinement on rock mass modulus: A synthetic rock mass modelling (SRM study

    Directory of Open Access Journals (Sweden)

    I. Vazaios

    2018-06-01

    Full Text Available The main objective of this paper is to examine the influence of the applied confining stress on the rock mass modulus of moderately jointed rocks (well interlocked undisturbed rock mass with blocks formed by three or less intersecting joints. A synthetic rock mass modelling (SRM approach is employed to determine the mechanical properties of the rock mass. In this approach, the intact body of rock is represented by the discrete element method (DEM-Voronoi grains with the ability of simulating the initiation and propagation of microcracks within the intact part of the model. The geometry of the pre-existing joints is generated by employing discrete fracture network (DFN modelling based on field joint data collected from the Brockville Tunnel using LiDAR scanning. The geometrical characteristics of the simulated joints at a representative sample size are first validated against the field data, and then used to measure the rock quality designation (RQD, joint spacing, areal fracture intensity (P21, and block volumes. These geometrical quantities are used to quantitatively determine a representative range of the geological strength index (GSI. The results show that estimating the GSI using the RQD tends to make a closer estimate of the degree of blockiness that leads to GSI values corresponding to those obtained from direct visual observations of the rock mass conditions in the field. The use of joint spacing and block volume in order to quantify the GSI value range for the studied rock mass suggests a lower range compared to that evaluated in situ. Based on numerical modelling results and laboratory data of rock testing reported in the literature, a semi-empirical equation is proposed that relates the rock mass modulus to confinement as a function of the areal fracture intensity and joint stiffness. Keywords: Synthetic rock mass modelling (SRM, Discrete fracture network (DFN, Rock mass modulus, Geological strength index (GSI, Confinement

  17. Protein Kinases in Shaping Plant Architecture.

    Science.gov (United States)

    Wu, Juan; Wang, Bo; Xin, Xiaoyun; Ren, Dongtao

    2018-02-13

    Plant architecture, the three-dimensional organization of the plant body, includes the branching pattern and the size, shape, and position of organs. Plant architecture is genetically controlled and is influenced by environmental conditions. The regulations occur at most of the stages from the first division of the fertilized eggs to the final establishment of plant architecture. Among the various endogenous regulators, protein kinases and their associated signaling pathways have been shown to play important roles in regulating the process of plant architecture establishment. In this review, we summarize recent progress in the understanding of the mechanisms by which plant architecture formation is regulated by protein kinases, especially mitogen-activated protein kinase (MAPK). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. The Role of PAS Kinase in PASsing the Glucose Signal

    Directory of Open Access Journals (Sweden)

    Julianne H. Grose

    2010-06-01

    Full Text Available PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration.

  19. Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

    International Nuclear Information System (INIS)

    Grose, C.; Jackson, W.; Traugh, J.A.

    1989-01-01

    Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

  20. 2-Aminobenzimidazoles as potent Aurora kinase inhibitors.

    Science.gov (United States)

    Zhong, Min; Bui, Minna; Shen, Wang; Baskaran, Subramanian; Allen, Darin A; Elling, Robert A; Flanagan, W Michael; Fung, Amy D; Hanan, Emily J; Harris, Shannon O; Heumann, Stacey A; Hoch, Ute; Ivy, Sheryl N; Jacobs, Jeffrey W; Lam, Stuart; Lee, Heman; McDowell, Robert S; Oslob, Johan D; Purkey, Hans E; Romanowski, Michael J; Silverman, Jeffrey A; Tangonan, Bradley T; Taverna, Pietro; Yang, Wenjin; Yoburn, Josh C; Yu, Chul H; Zimmerman, Kristin M; O'Brien, Tom; Lew, Willard

    2009-09-01

    This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2-Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314.

  1. Biogenic Cracks in Porous Rock

    Science.gov (United States)

    Hemmerle, A.; Hartung, J.; Hallatschek, O.; Goehring, L.; Herminghaus, S.

    2014-12-01

    Microorganisms growing on and inside porous rock may fracture it by various processes. Some of the mechanisms of biofouling and bioweathering are today identified and partially understood but most emphasis is on chemical weathering, while mechanical contributions have been neglected. However, as demonstrated by the perseverance of a seed germinating and cracking up a concrete block, the turgor pressure of living organisms can be very significant. Here, we present results of a systematic study of the effects of the mechanical forces of growing microbial populations on the weathering of porous media. We designed a model porous medium made of glass beads held together by polydimethylsiloxane (PDMS), a curable polymer. The rheological properties of the porous medium, whose shape and size are tunable, can be controlled by the ratio of crosslinker to base used in the PDMS (see Fig. 1). Glass and PDMS being inert to most chemicals, we are able to focus on the mechanical processes of biodeterioration, excluding any chemical weathering. Inspired by recent measurements of the high pressure (~0.5 Mpa) exerted by a growing population of yeasts trapped in a microfluidic device, we show that yeast cells can be cultured homogeneously within porous medium until saturation of the porous space. We investigate then the effects of such an inner pressure on the mechanical properties of the sample. Using the same model system, we study also the complex interplay between biofilms and porous media. We focus in particular on the effects of pore size on the penetration of the biofilm within the porous sample, and on the resulting deformations of the matrix, opening new perspectives into the understanding of life in complex geometry. Figure 1. Left : cell culture growing in a model porous medium. The white spheres represent the grains, bonds are displayed in grey, and microbes in green. Right: microscopy picture of glass beads linked by PDMS bridges, scale bar: 100 μm.

  2. Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei

    Science.gov (United States)

    Li, H.; Roux, S. J.

    1992-01-01

    Almost all the polyamine-stimulated protein kinase activity associated with the chromatin fraction of nuclei purified from etiolated pea (Pisum sativum L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.35 molar NaCl. This protein kinase can be further purified over 2000-fold by salt fractionation and anion-exchange and casein-agarose column chromatography, after which it is more than 90% pure. The purified kinase has a specific activity of about 650 nanomoles per minute per milligram protein in the absence of polyamines, with either ATP or GTP as phosphoryl donor. Spermidine can stimulate its activity fourfold, with half-maximal activation at about 2 millimolar. Spermine and putrescine also stimulate activity, although somewhat less effectively. This kinase has a tetrameric alpha 2 beta 2 structure with a native molecular weight of 130,000, and subunit molecular weights of 36,000 for the catalytic subunit (alpha) and 29,000 for the regulatory subunit (beta). In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II. The pea kinase can use casein and phosvitin as artificial substrates, phosphorylating both the serine and threonine residues of casein. It has a pH optimum near 8.0, a Vmax of 1.5 micromoles per minute per milligram protein, and a Km for ATP of approximately 75 micromolar. Its activity can be almost completely inhibited by heparin at 5 micrograms per milliliter, but is relatively insensitive to concentrations of staurosporine, K252a, and chlorpromazine that strongly antagonize Ca(2+) -regulated protein kinases. These results are discussed in relation to recent findings that casein kinase 2-type kinases may phosphorylate trans-acting factors that bind to light-regulated promoters in plants.

  3. CZK3, a MAP kinase kinase kinase homolog in Cercospora zeae-maydis, regulates cercosporin biosynthesis, fungal development, and pathogenesis.

    Science.gov (United States)

    Shim, Won-Bo; Dunkle, Larry D

    2003-09-01

    The fungus Cercospora zeae-maydis causes gray leaf spot of maize and produces cercosporin, a photosensitizing perylenequinone with toxic activity against a broad spectrum of organisms. However, little is known about the biosynthetic pathway or factors that regulate cercosporin production. Analysis of a cDNA subtraction library comprised of genes that are up-regulated during cercosporin synthesis revealed a sequence highly similar to mitogen-activated protein (MAP) kinases in other fungi. Sequencing and conceptual translation of the full-length genomic sequence indicated that the gene, which we designated CZK3, contains a 4,119-bp open reading frame devoid of introns and encodes a 1,373-amino acid sequence that is highly similar to Wis4, a MAP kinase kinase kinase in Schizosaccharomyces pombe. Targeted disruption of CZK3 suppressed expression of genes predicted to participate in cercosporin biosynthesis and abolished cercosporin production. The disrupted mutants grew faster on agar media than the wild type but were deficient in conidiation and elicited only small chlorotic spots on inoculated maize leaves compared with rectangular necrotic lesions incited by the wild type. Complementation of disruptants with the CZK3 open reading frame and flanking sequences restored wild-type levels of conidiation, growth rate, and virulence as well as the ability to produce cercosporin. The results suggest that cercosporin is a virulence factor in C. zeae-maydis during maize pathogenesis, but the pleiotropic effects of CZK3 disruption precluded definitive conclusions.

  4. Wing rock suppression using forebody vortex control

    Science.gov (United States)

    Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

    1991-01-01

    Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

  5. RELIABILITY OF TRANSPORTATION SYSTEMS OF ROCK HAPS

    Directory of Open Access Journals (Sweden)

    A. Stepanov

    2009-01-01

    Full Text Available The ways of increasing of exploitation reliability of dump trucks with the aim of increasing of effectiveness of exploitation of transportation systems of rock heaps at coal mines.

  6. Rock bed heat accumulators. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Riaz, M.

    1977-12-01

    The principal objectives of the research program on rock bed heat accumulators (or RBHA) are: (1) to investigate the technical and economic feasibility of storing large amounts of thermal energy (in the tens of MWt range) at high temperature (up to 500/sup 0/C) over extended periods of time (up to 6 months) using native earth or rock materials; (2) to conduct studies to establish the performance characteristics of large rock bed heat accumulators at various power and temperature levels compatible with thermal conversion systems; and (3) to assess the materials and environmental problems associated with the operation of such large heat accumulators. Results of the study indicate that rock bed heat accumulators for seasonal storage are both technically and economically feasible, and hence could be exploited in various applications in which storage plays an essential role such as solar power and total energy systems, district and cogeneration heating systems.

  7. Cretaceous rocks of the Western Interior basin

    International Nuclear Information System (INIS)

    Molenaar, C.M.; Rice, D.D.

    1988-01-01

    The Cretaceous rocks of the conterminous United States are discussed in this chapter. Depositional facies and lithology are reviewed along with economic resources. The economic resources include coal, hydrocarbons, and uranium

  8. Mechanical dispersion in fractured crystalline rock systems

    International Nuclear Information System (INIS)

    Lafleur, D.W.; Raven, K.G.

    1986-12-01

    This report compiles and evaluates the hydrogeologic parameters describing the flow of groundwater and transport of solutes in fractured crystalline rocks. This report describes the processes of mechanical dispersion in fractured crystalline rocks, and compiles and evaluates the dispersion parameters determined from both laboratory and field tracer experiments. The compiled data show that extrapolation of the reliable test results performed over intermediate scales (10's of m and 10's to 100's of hours) to larger spatial and temporal scales required for performance assessment of a nuclear waste repository in crystalline rock is not justified. The reliable measures of longitudinal dispersivity of fractured crystalline rock are found to range between 0.4 and 7.8 m

  9. Dating oxalate minerals in rock surface deposits

    International Nuclear Information System (INIS)

    Watchman, A.

    2001-01-01

    Oxalate minerals are found associated with rocks, mineral coatings, micro-organisms, plants and animals. They are important in archaeology because they have been found intimately associated with organic binders in prehistoric paints. Oxalate minerals also accumulate in the coatings on rock shelter walls and fallen ceiling slabs where they form the natural backing supports for painting and opaque laminates covering engravings. Though the relationship between anthropogenic activity in a rock shelter and oxalate formation is often uncertain, the radiocarbon age of the oxalate may provide the only means for determining the antiquity of a rock painting or engraving. This paper examines the history of dating oxalate minerals at archaeological sites and provides insights into achieving reliable age estimates. (author). 37 refs., 1 fig., 2 tabs

  10. ROCK GLACIERS IN THE KOLYMA HIGHLAND

    Directory of Open Access Journals (Sweden)

    A. A. Galanin

    2012-01-01

    Full Text Available Based on remote mapping and field studies inGrand Rapids, Tumansky,Hasynsky,Del-Urechen Ridges as well as Dukchinsky and Kilgansky Mountain Massifs there were identified about 1160 landforms which morphologically are similar to the rock glaciers or they develop in close association with them. Besides tongue-shaped cirque rock glaciers originated due to ablation, a large number of lobate-shaped slope-associated rock glaciers were recognized. Significant quantity of such forms are developing within the active neotectonic areas, in zones of seismic-tectonic badland and in association with active earthquakes-controlling faults. Multiplication of regional data on volcanic-ash-chronology, lichenometry, Schmidt Hammer Test, pollen spectra and single radiocarbon data, most of the active rock glaciers were preliminary attributed to the Late Holocene.

  11. Rock glaciers, Prealps, Vaud, Switzerland, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The investigated area forms part of the western lobe of the Prealps (Swiss Prealps). The 25 identified fossil rock glaciers are found mainly in the Prealpes medianes...

  12. Mechanical properties of rock at high temperatures

    International Nuclear Information System (INIS)

    Kinoshita, Naoto; Abe, Tohru; Wakabayashi, Naruki; Ishida, Tsuyoshi.

    1997-01-01

    The laboratory tests have been performed in order to investigate the effects of temperature up to 300degC and pressure up to 30 MPa on the mechanical properties of three types of rocks, Inada granite, Sanjoume andesite and Oya tuff. The experimental results indicated that the significant differences in temperature dependence of mechanical properties exist between the three rocks, because of the difference of the factors which determine the mechanical properties of the rocks. The effect of temperature on the mechanical properties for the rocks is lower than that of pressure and water content. Temperature dependence of the mechanical properties is reduced by increase in pressure in the range of pressure and temperature investigated in this paper. (author)

  13. Pore-scale analysis of electrical properties in thinly bedded rock using digital rock physics

    International Nuclear Information System (INIS)

    Sun, Jianmeng; Zhao, Jianpeng; Liu, Xuefeng; Chen, Hui; Jiang, LiMing; Zhang, JinYan

    2014-01-01

    We investigated the electrical properties of laminated rock consist of macro-porous layers and micro-porous layers based on digital rock technology. Due to the bedding effect and anisotropy, traditional Archie equations cannot well describe the electrical behavior of laminated rock. The RI-Sw curve of laminated rock shows a nonlinear relationship. The RI-Sw curve can be divided into two linear segments with different saturation exponent. Laminated sand-shale sequences and laminated sands of different porosity or grain size will yield macroscopic electrical anisotropy. Numerical simulation and theoretical analysis lead to the conclusion that electrical anisotropy coefficient of laminated rock is a strong function of water saturation. The function curve can be divided into three segments by the turning point. Therefore, the electrical behavior of laminated rock should be considered in oil exploration and development. (paper)

  14. Evaluation of dynamic characteristics of hard rock based on numerical simulations of in situ rock tests

    International Nuclear Information System (INIS)

    Yamagami, Yuya; Ikusada, Koji; Jiang, Yujing

    2009-01-01

    In situ rock tests of hard rock of conglomerate in which discontinuities in high angle are dominant were conducted. In this study, in order to confirm the validity of the test results and the test condition, and in order to elucidate the deformation behaviour and the mechanism of shear strength of the rock mass, the numerical simulations of the in situ rock tests by using distinct element method were performed. As a result, it was clarified that the behaviour of the rock mass strongly depends on both geometrical distribution of discontinuities and those mechanical properties. It is thought that a series of evaluation processes showed in this study contribute to improve the reliability of the dynamic characteristic evaluation of the rock mass. (author)

  15. ONKALO rock mechanics model (RMM). Version 2.3

    Energy Technology Data Exchange (ETDEWEB)

    Haekkinen, T.; Merjama, S.; Moenkkoenen, H. [WSP Finland, Helsinki (Finland)

    2014-07-15

    The Rock Mechanics Model of the ONKALO rock volume includes the most important rock mechanics features and parameters at the Olkiluoto site. The main objective of the model is to be a tool to predict rock properties, rock quality and hence provide an estimate for the rock stability of the potential repository at Olkiluoto. The model includes a database of rock mechanics raw data and a block model in which the rock mechanics parameters are estimated through block volumes based on spatial rock mechanics raw data. In this version 2.3, special emphasis was placed on refining the estimation of the block model. The model was divided into rock mechanics domains which were used as constraints during the block model estimation. During the modelling process, a display profile and toolbar were developed for the GEOVIA Surpac software to improve visualisation and access to the rock mechanics data for the Olkiluoto area. (orig.)

  16. Relating rock avalanche morphology to emplacement processes

    Science.gov (United States)

    Dufresne, Anja; Prager, Christoph; Bösmeier, Annette

    2015-04-01

    The morphology, structure and sedimentological characteristics of rock avalanche deposits reflect both internal emplacement processes and external influences, such as runout path characteristics. The latter is mainly predisposed by topography, substrate types, and hydrogeological conditions. Additionally, the geological setting at the source slope controls, e.g. the spatial distribution of accumulated lithologies and hence material property-related changes in morphology, or the maximum clast size and amount of fines of different lithological units. The Holocene Tschirgant rock avalanche (Tyrol, Austria) resulted from failure of an intensely deformed carbonate rock mass on the southeast face of a 2,370-m-high mountain ridge. The initially sliding rock mass rapidly fragmented as it moved towards the floor of the Inn River valley. Part of the 200-250 x 106 m3 (Patzelt 2012) rock avalanche debris collided with and moved around an opposing bedrock ridge and flowed into the Ötz valley, reaching up to 6.3 km from source. Where the Tschirgant rock avalanche spread freely it formed longitudinal ridges aligned along motion direction as well as smaller hummocks. Encountering high topography, it left runup ridges, fallback patterns (i.e. secondary collapse), and compressional morphology (successively elevated, transverse ridges). Further evidence for the mechanical landslide behaviour is given by large volumes of mobilized valley-fill sediments (polymict gravels and sands). These sediments indicate both shearing and compressional faulting within the rock avalanche mass (forming their own morphological units through, e.g. in situ bulldozing or as distinctly different hummocky terrain), but also indicate extension of the spreading landslide mass (i.e. intercalated/injected gravels encountered mainly in morphological depressions between hummocks). Further influences on its morphology are given by the different lithological units. E.g. the transition from massive dolomite

  17. Myosin light chain kinase phosphorylation in tracheal smooth muscle

    International Nuclear Information System (INIS)

    Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

    1990-01-01

    Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

  18. Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights

    DEFF Research Database (Denmark)

    Niefind, K; Raaf, J; Issinger, Olaf-Georg

    2009-01-01

    the critical region of CK2alpha recruitment is pre-formed in the unbound state. In CK2alpha the activation segment - a key element of protein kinase regulation - adapts invariably the typical conformation of the active enzymes. Recent structures of human CK2alpha revealed a surprising plasticity in the ATP......Within the last decade, 40 crystal structures corresponding to protein kinase CK2 (former name 'casein kinase 2'), to its catalytic subunit CK2alpha and to its regulatory subunit CK2beta were published. Together they provide a valuable, yet by far not complete basis to rationalize the biochemical...

  19. Remarks on some rock neutron parameters

    International Nuclear Information System (INIS)

    Czubek, J.A.

    1984-01-01

    A method to calculate the thermal neutron parameters of rocks is given in the paper. It is based on a proper energy averaging of cross-sections for all rock matrix and rock saturating liquid constituents. The diffusion lengths in different lithologies in function of the variable rock porosity have been calculated. An influence of the thermal neutron spectrum on the shape of the porosity calibration curves for the dual spacing neutron method is shown. Magmatic rocks as a possible source of geothermal energy are now becoming a target of neutron loggings for the porosity determination. Here the knowledge of the slowing-down lengths is of great importance in the problem of the estimation of the calibration curves. A semi-analytical approach to get this parameter is given in the paper. It was found, as far as concerns the slowing-down of fast neutrons, that all magmatic rocks behave as sandstone with, however, different content of bound water in the rock matrix and different rock matrix density. Some neutron methods are based on the detection of epithermal neutrons. For theoretical considerations it is important to know the physical meaning of the registered signal. From the discussion of experimental data reported in the literature it seems that it is the slowing-down density that is the physical quantity being measured. This conclusion has a very important practical implication - the porosity calibration curves depend upon the slowing-down length alone and are independent of the slowing-down cross-section for epithermal neutrons

  20. Digital Rock Studies of Tight Porous Media

    Energy Technology Data Exchange (ETDEWEB)

    Silin, Dmitriy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-08-07

    This technical report summarizes some recently developed approaches to studies of rock properties at a pore scale. Digital rock approach is complementary to laboratory and field studies. It can be especially helpful in situations where experimental data are uncertain, or are difficult or impossible to obtain. Digitized binary images of the pore geometries of natural rocks obtained by different imaging techniques are the input data. Computer-generated models of natural rocks can be used instead of images in a case where microtomography data are unavailable, or the resolution of the tools is insufficient to adequately characterize the features of interest. Simulations of creeping viscous flow in pores produce estimates of Darcy permeability. Maximal Inscribed Spheres calculations estimate two-phase fluid distribution in capillary equilibrium. A combination of both produce relative permeability curves. Computer-generated rock models were employed to study two-phase properties of fractured rocks, or tight sands with slit-like pores, too narrow to be characterized with micro-tomography. Various scenarios can simulate different fluid displacement mechanisms, from piston-like drainage to liquid dropout at the dew point. A finite differences discretization of Stokes equation is developed to simulate flow in the pore space of natural rocks. The numerical schemes are capable to handle both no-slip and slippage flows. An upscaling procedure estimates the permeability by subsampling a large data set. Capillary equilibrium and capillary pressure curves are efficiently estimated with the method of maximal inscribed spheres both an arbitrary contact angle. The algorithms can handle gigobytes of data on a desktop workstation. Customized QuickHull algorithms model natural rocks. Capillary pressure curves evaluated from computer-generated images mimic those obtained for microtomography data.

  1. Rock excavation by pulsed electron beams

    International Nuclear Information System (INIS)

    Avery, R.T.; Keefe, D.; Brekke, T.L.; Finnie, I.

    1976-03-01

    If an intense short pulse of megavolt electrons is deposited in a brittle solid, dynamic spalling can be made to occur with removal of material. Experiments were made on several types of hard rock; results are reproducible and well-described theoretically. An accelerator with a rapidly-pulsed scanning electron beam was designed that could tunnel in hard rock about ten times faster than conventional drill/blast methods

  2. Rock excavation by pulsed electron beams

    International Nuclear Information System (INIS)

    Avery, R.T.; Keefe, D.; Brekke, T.L.; Finnie, I.

    1976-01-01

    If an intense short pulse of megavolt electrons is deposited in a brittle solid, dynamic spalling can be made to occur with removal of material. Experiments have been made on several types of hard rock; results are reproducible and well-described theoretically. An accelerator with a rapid-pulsed scanning electron-beam has been designed that could tunnel in hard rock about ten times faster than conventional drill/blast methods. (author)

  3. The Dalradian rocks of Scotland: an introduction

    OpenAIRE

    Stephenson, David; Mendum, John R.; Fettes, Douglas J.; Leslie, A. Graham

    2013-01-01

    The Dalradian Supergroup and its basement rocks, together with younger plutons, underpin most of the Grampian Highlands and the islands of the Inner Hebrides between the Highland Boundary and Great Glen faults. The Dalradian is a mid-Neoproterozoic to early-Ordovician sequence of largely clastic metasedimentary rocks, with some volcanic units, which were deformed and metamorphosed to varying degrees during the Early Palaeozoic Caledonian Orogeny. Sedimentation of the lower parts of the Da...

  4. Developing a Virtual Rock Deformation Laboratory

    Science.gov (United States)

    Zhu, W.; Ougier-simonin, A.; Lisabeth, H. P.; Banker, J. S.

    2012-12-01

    Experimental rock physics plays an important role in advancing earthquake research. Despite its importance in geophysics, reservoir engineering, waste deposits and energy resources, most geology departments in U.S. universities don't have rock deformation facilities. A virtual deformation laboratory can serve as an efficient tool to help geology students naturally and internationally learn about rock deformation. Working with computer science engineers, we built a virtual deformation laboratory that aims at fostering user interaction to facilitate classroom and outreach teaching and learning. The virtual lab is built to center around a triaxial deformation apparatus in which laboratory measurements of mechanical and transport properties such as stress, axial and radial strains, acoustic emission activities, wave velocities, and permeability are demonstrated. A student user can create her avatar to enter the virtual lab. In the virtual lab, the avatar can browse and choose among various rock samples, determine the testing conditions (pressure, temperature, strain rate, loading paths), then operate the virtual deformation machine to observe how deformation changes physical properties of rocks. Actual experimental results on the mechanical, frictional, sonic, acoustic and transport properties of different rocks at different conditions are compiled. The data acquisition system in the virtual lab is linked to the complied experimental data. Structural and microstructural images of deformed rocks are up-loaded and linked to different deformation tests. The integration of the microstructural image and the deformation data allows the student to visualize how forces reshape the structure of the rock and change the physical properties. The virtual lab is built using the Game Engine. The geological background, outstanding questions related to the geological environment, and physical and mechanical concepts associated with the problem will be illustrated on the web portal. In

  5. Rock Moved by Mars Lander Arm

    Science.gov (United States)

    2008-01-01

    The robotic arm on NASA's Phoenix Mars Lander slid a rock out of the way during the mission's 117th Martian day (Sept. 22, 2008) to gain access to soil that had been underneath the rock.The lander's Surface Stereo Imager took the two images for this stereo view later the same day, showing the rock, called 'Headless,' after the arm pushed it about 40 centimeters (16 inches) from its previous location. 'The rock ended up exactly where we intended it to,' said Matt Robinson of NASA's Jet Propulsion Laboratory, robotic arm flight software lead for the Phoenix team. The arm had enlarged the trench near Headless two days earlier in preparation for sliding the rock into the trench. The trench was dug to about 3 centimeters (1.2 inches) deep. The ground surface between the rock's prior position and the lip of the trench had a slope of about 3 degrees downward toward the trench. Headless is about the size and shape of a VHS videotape. The Phoenix science team sought to move the rock in order to study the soil and the depth to subsurface ice underneath where the rock had been. This image was taken at about 12:30 p.m., local solar time on Mars. The view is to the north northeast of the lander. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by JPL, Pasadena, Calif. Spacecraft development was by Lockheed Martin Space Systems, Denver.

  6. Preliminary rock mechanics laboratory: Investigation plan

    International Nuclear Information System (INIS)

    Oschman, K.P.; Hummeldorf, R.G.; Hume, H.R.; Karakouzian, M.; Vakili, J.E.

    1987-01-01

    This document presents the rationale for rock mechanics laboratory testing (including the supporting analysis and numerical modeling) planned for the site characterization of a nuclear waste repository in salt. This plan first identifies what information is required for regulatory and design purposes, and then presents the rationale for the testing that satisfies the required information needs. A preliminary estimate of the minimum sampling requirements for rock laboratory testing during site characterization is also presented. Periodic revision of this document is planned

  7. Nuclear power in rock. Principal report

    International Nuclear Information System (INIS)

    1977-06-01

    In September 1975 the Swedish Government directed the Swedish State Power Board to study the question of rock-siting nuclear power plants. The study accounted for in this report aims at clarifying the advantages and disadvantages of siting a nuclear power plant in rock, compared to siting on ground level, considering reactor safety, war protection and sabotage. The need for nuclear power production during war situations and the closing down of nuclear power plants after terminated operation are also dealt with. (author)

  8. Underground large scale test facility for rocks

    International Nuclear Information System (INIS)

    Sundaram, P.N.

    1981-01-01

    This brief note discusses two advantages of locating the facility for testing rock specimens of large dimensions in an underground space. Such an environment can be made to contribute part of the enormous axial load and stiffness requirements needed to get complete stress-strain behavior. The high pressure vessel may also be located below the floor level since the lateral confinement afforded by the rock mass may help to reduce the thickness of the vessel

  9. Method of degassifying a massive of rock

    Energy Technology Data Exchange (ETDEWEB)

    Levin, M M; Krivosheev, V O; Preobrazhenskaia, E I; Talapkerov, A Sh; Taushkin, G T

    1979-05-30

    This invention concerns the mining industry, chiefly the coal industry, and can be used for the degasification of coal layers and interfering rock. The method of preliminary extraction of gas with underground development of burning minerals, including the pumping of gas through a collector, carried in the plane of the degasifying layer, discharged from rock pressure by means of extracting the lower lying layer, is known. However, the given method does not make it possible to degasify the interfering rock. Another method, consisting of the fact that from the mining development in the lateral rock, chambers are made, from which a group of wells are bored, and the latter are united with the gas removing system, is well known. This method has the inadequacy that the well of each chamber is connected to the gas removing system of the pipelines, and this leads to an increase in the price of the method. A new system is presented for the degasification of the massive of rock which is presented in an illustration...... The advantage of the suggested method consists of the fact that material outlays are reduced for the unification of each chamber with the gas removing pipeline, and besides this, the wells, connecting the chambers are drains for the surrounding rock, which increases the effectiveness of the degasification.

  10. The Rock that Hit New York

    Energy Technology Data Exchange (ETDEWEB)

    Meade, Roger Allen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Keksis, August Lawrence [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-03

    On January 12, 1975, a rock seemed to fall from the sky over New York State’s Schoharie County hitting the tractor of a local farmer, who was “preparing his fields for spring planting.” As the farmer later described the event to a reporter from the UFO INVESTIGATOR, the object glanced off the tractor, fell to the ground, and melted its way through a patch of ice that was two and one half inches thick. The farmer, Leonard Tillapaugh, called the county sheriff, Harvey Stoddard, who recovered the rock, noting that it “was still warm.” Why and how a sample of the rock came to Los Alamos is not known. However, it captivated a wide Laboratory audience, was subjected to rigorous testing and evaluation. Los Alamos used the scientific method in the manner promoted by Hynek. Did Los Alamos solve the mystery of the rock’s origin? Not definitively. Although the exact origin could not be determined, it was shown conclusively that the rock was not from outer space. With that said, the saga of Rock that hit New York came to an end. Nothing more was said or written about it. The principals involved have long since passed from the scene. The NICAP ceased operations in 1980. And, the rock, itself, has disappeared.

  11. Investigation of the porosity of rocks

    International Nuclear Information System (INIS)

    Hellmuth, K.H.; Siitari-Kauppi, M.

    1990-06-01

    Methods for characterizing the nature of rock porosity in conjunction with diffusion experiments, are amongst the primary tools used in repository-site selection investigations. At this time no experimental method, alone, is capable of giving an unambiguous picture of the narrow-aperture pore space in crystalline rock. Methods giving information on overall properties must be complemented by those having high spatial resolution; then the lateral distribution of porosity within the matrix and its association with particular mineral phases or features, such as microfissures, fissure fillings, weathered or altered mineral phases etc, and the identification of diffusion pathways in inhomogeneous rock matrices can be determined. Nonsorbing, nonelectrolytic tracers should be used when one wants to determine rock-typical properties of the internal porosity without interference of interactions with surfaces. Preliminary information on a new method fulfilling these criteria is given. Impregnating rock samples with methylmethacrylate labeled with carbon-14 which, after impregnation, was polymerized by gamma radiation, gave specimens that made preparation of sections suitable for quantification by autoradiographic methods easy. Diffusion experiments can be conducted so that labeled MMA diffuses out of rock specimens into inactive free, MMA. Additional information may be gained by leaching PMMA fractions of lower molecular weight from the matrix

  12. Rock burst prevention at steep seam mining

    Energy Technology Data Exchange (ETDEWEB)

    Efremov, G D

    1988-09-01

    At steep shield longwalls one method of preventing rock bursts is to avoid sharp angles during working. Stress in coal and rock body that appears when steep seams are worked where rock bursts occur at corners of set-up entries is discussed. The dynamic interaction between gas and rock pressure is assessed. Maintains that in order to avoid rock bursts at these places it is necessary to turn the protruding coal wall by 20-30 degrees towards the coal body to divert the action of shift forces. At the same time the face should also be inclined (by 10-15 degrees) to move the zones of increased stress away from the corner into the coal and rock body. Stress at workings with round cross-sections is 3-4 times lower than at square cross-sections. Recommendations are given that concern shearer loader operation (semi-spherical shape of the face), borehole drilling and water injection. Initial distance of 10-15 m between boreholes is suggested. 3 refs.

  13. Radionuclide migration in crystalline rock fractures

    International Nuclear Information System (INIS)

    Hoelttae, P.

    2002-01-01

    Crystalline rock has been considered as a host medium for the repository of high radioactive spent nuclear fuel in Finland. The geosphere will act as an ultimate barrier retarding the migration of radionuclides to the biosphere if they are released through the technical barriers. Radionuclide transport is assumed to take place along watercarrying fractures, and retardation will occur both in the fracture and within the rock matrix. To be able to predict the transport and retardation of radionuclides in rock fractures and rock matrices, it is essential to understand the different phenomena involved. Matrix diffusion has been indicated to be an important mechanism, which will retard the transport of radionuclides in rock fractures. Both dispersion and matrix diffusion are processes, which can have similar influences on solute breakthrough curves in fractured crystalline rock. In this work, the migration of radionuclides in crystalline rock fractures was studied by means of laboratory scale column methods. The purpose of the research was to gain a better understanding of various phenomena - particularly matrix diffusion - affecting the transport and retardation behaviour of radionuclides in fracture flow. Interaction between radionuclides and the rock matrix was measured in order to test the compatibility of experimental retardation parameters and transport models used in assessing the safety of underground repositories for spent nuclear fuel. Rock samples of mica gneiss and of unaltered, moderately altered and strongly altered tonalite represented different rock features and porosities offering the possibility to determine experimental boundary limit values for parameters describing both the transport and retardation of radionuclides and rock matrix properties. The dominant matrix diffusion behaviour was demonstrated in porous ceramic column and gas diffusion experiments. Demonstration of the effects of matrix diffusion in crystalline rock fracture succeeded for the

  14. Side-effects of protein kinase inhibitors on ion channels

    Indian Academy of Sciences (India)

    2013-11-06

    Nov 6, 2013 ... with aberrant kinase activity, including cancers, arthritis and cardiovascular disorders. Several strategies .... family, the β-adrenergic receptor kinase (βARK), the ribosomal S6 ..... urinary bladder smooth muscle cells. While no ...

  15. Creatine kinase activity is associated with blood pressure

    NARCIS (Netherlands)

    Brewster, Lizzy M.; Mairuhu, Gideon; Bindraban, Navin R.; Koopmans, Richard P.; Clark, Joseph F.; van Montfrans, Gert A.

    2006-01-01

    BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular

  16. Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine

    DEFF Research Database (Denmark)

    Knecht, Wolfgang; Mikkelsen, N.E.; Clausen, A.R.

    2009-01-01

    Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) can additionally sensitize human cancer cell lines towards the anti-cancer drug gemcitabine. We show that this property is based on the Dm-dNK ability to efficiently phosphorylate gemcitabine. The 2.2 angstrom resolution...

  17. Deoxyribonucleoside kinases in mitochondrial DNA depletion.

    Science.gov (United States)

    Saada-Reisch, Ann

    2004-10-01

    Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of mitochondrial disorders, manifested by a decreased mtDNA copy number and respiratory chain dysfunction. Primary MDS are inherited autosomally and may affect a single organ or multiple tissues. Mutated mitochondrial deoxyribonucleoside kinases; deoxyguanosine kinase (dGK) and thymidine kinase 2 (TK2), were associated with the hepatocerebral and myopathic forms of MDS respectively. dGK and TK2 are key enzymes in the mitochondrial nucleotide salvage pathway, providing the mitochondria with deoxyribonucleotides (dNP) essential for mtDNA synthesis. Although the mitochondrial dNP pool is physically separated from the cytosolic one, dNP's may still be imported through specific transport. Non-replicating tissues, where cytosolic dNP supply is down regulated, are thus particularly vulnerable to dGK and TK2 deficiency. The overlapping substrate specificity of deoxycytidine kinase (dCK) may explain the relative sparing of muscle in dGK deficiency, while low basal TK2 activity render this tissue susceptible to TK2 deficiency. The precise pathophysiological mechanisms of mtDNA depletion due to dGK and TK2 deficiencies remain to be determined, though recent findings confirm that it is attributed to imbalanced dNTP pools.

  18. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    current barriers of kinase inhibitors, including poor selectivity and emergence of drug resistance. In spite of the small number of identified allosteric inhibitors in comparison with that of inhibitors targeting the ATP pocket, encouraging results, such as the FDA-approval of the first small...

  19. Plant PA signaling via diacylglycerol kinase

    NARCIS (Netherlands)

    Arisz, S.A.; Testerink, C.; Munnik, T.

    2009-01-01

    Accumulating evidence suggests that phosphatidic acid (PA) plays a pivotal role in the plant's response to environmental signals. Besides phospholipase D (PLD) activity, PA can also be generated by diacylglycerol kinase (DGK). To establish which metabolic route is activated, a differential

  20. Nonorthologous gene displacement of phosphomevalonate kinase

    NARCIS (Netherlands)

    Houten, S. M.; Waterham, H. R.

    2001-01-01

    Phosphomevalonate kinase (PMK; EC 2.7.4.2) catalyzes the phosphorylation of 5-phosphomevalonate into 5-diphosphomevalonate, an essential step in isoprenoid biosynthesis via the mevalonate pathway. So far, two nonorthologous genes encoding PMK have been described, the Saccharomyces cerevisiae ERG8

  1. Casein kinase-2 structure-function relationship

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Pinna, L A

    1992-01-01

    Nine mutants of human casein kinase-2 beta subunit have been created and assayed for their ability to assemble with the catalytic alpha subunit to give, at a 1:1 molar ratio, a fully competent CK-2 holoenzyme as judged by the following criteria: 1) the generation of an active heterotetrameric form...

  2. Mitogen-activated protein kinases mediate Mycobacterium ...

    Indian Academy of Sciences (India)

    2012-01-19

    Jan 19, 2012 ... CD44, an adhesion molecule, has been reported to be a binding site for ... receptors in mediating mitogen-activated protein kinase activation. ... surface expression and tumour necrosis factor-alpha levels, ... Abbreviations used: Abs, antibodies; ANOVA, analysis of variance; AP-1, activator protein -1; BCG, ...

  3. Kinase-Centric Computational Drug Development

    NARCIS (Netherlands)

    Kooistra, Albert J.; Volkamer, Andrea

    2017-01-01

    Kinases are among the most studied drug targets in industry and academia, due to their involvement in a majority of cellular processes and, upon dysregulation, in a variety of diseases including cancer, inflammation, and autoimmune disorders. The high interest in this druggable protein family

  4. Kinases involved in Rec8 phosphorylation revealed

    Czech Academy of Sciences Publication Activity Database

    Anger, Martin

    2010-01-01

    Roč. 9, č. 14 (2010), s. 2708-2708 ISSN 1538-4101 Institutional research plan: CEZ:AV0Z50450515 Keywords : kinases * Rec8 * meisosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.999, year: 2010

  5. Gene regulation by MAP kinase cascades

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Petersen, Klaus; Petersen, Morten

    2009-01-01

    Mitogen-activated protein kinase (MAPK) cascades are signaling modules that transduce extracellular stimuli to a range of cellular responses. Research in yeast and metazoans has shown that MAPK-mediated phosphorylation directly or indirectly regulates the activity of transcription factors. Plant ...

  6. Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets.

    Science.gov (United States)

    Lai, Justine Y Q; Langston, Steven; Adams, Ruth; Beevers, Rebekah E; Boyce, Richard; Burckhardt, Svenja; Cobb, James; Ferguson, Yvonne; Figueroa, Eva; Grimster, Neil; Henry, Andrew H; Khan, Nawaz; Jenkins, Kerry; Jones, Mark W; Judkins, Robert; Major, Jeremy; Masood, Abid; Nally, James; Payne, Helen; Payne, Lloyd; Raphy, Gilles; Raynham, Tony; Reader, John; Reader, Valérie; Reid, Alison; Ruprah, Parminder; Shaw, Michael; Sore, Hannah; Stirling, Matthew; Talbot, Adam; Taylor, Jess; Thompson, Stephen; Wada, Hiroki; Walker, David

    2005-05-01

    This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection. Copyright (c) 2004 Wiley Periodicals, Inc.

  7. Kinase detection with gallium nitride based high electron mobility transistors.

    Science.gov (United States)

    Makowski, Matthew S; Bryan, Isaac; Sitar, Zlatko; Arellano, Consuelo; Xie, Jinqiao; Collazo, Ramon; Ivanisevic, Albena

    2013-07-01

    A label-free kinase detection system was fabricated by the adsorption of gold nanoparticles functionalized with kinase inhibitor onto AlGaN/GaN high electron mobility transistors (HEMTs). The HEMTs were operated near threshold voltage due to the greatest sensitivity in this operational region. The Au NP/HEMT biosensor system electrically detected 1 pM SRC kinase in ionic solutions. These results are pertinent to drug development applications associated with kinase sensing.

  8. Diversity, classification and function of the plant protein kinase superfamily

    OpenAIRE

    Lehti-Shiu, Melissa D.; Shiu, Shin-Han

    2012-01-01

    Eukaryotic protein kinases belong to a large superfamily with hundreds to thousands of copies and are components of essentially all cellular functions. The goals of this study are to classify protein kinases from 25 plant species and to assess their evolutionary history in conjunction with consideration of their molecular functions. The protein kinase superfamily has expanded in the flowering plant lineage, in part through recent duplications. As a result, the flowering plant protein kinase r...

  9. Marked dietary differences between sympatric feral rock doves and ...

    African Journals Online (AJOL)

    1993-06-24

    Jun 24, 1993 ... Although feral rock doves Columba Iivia and rock pigeons C. guinea fly daily in mixed flocks between roosting and nesting sites in Cape Town, South Africa, they feed separately in farmlands north of the city during the austral summer. Examination of the crop contents of 32 feral rock doves and 48 rock ...

  10. Marked dietary differences between sympatric feral rock doves and ...

    African Journals Online (AJOL)

    Although feral rock doves Columba livia and rock pigeons C. guineafly daily in mixed flocks between roosting and nesting sites in Cape Town, South Africa, they feed separately in farmlands north of the city during the austral summer. Examination of the crop contents of 32 feral rock doves and 48 rock pigeons revealed that ...

  11. p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Fu, Meng; Wang, Lifeng

    2013-01-01

    204) although phosphorylation of b-Raf (Ser445) and c-Raf (Ser 338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1 and Mek1, independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulate...... MEK activity in a kinase independent manner, probably by serving as a scaffold to facilitate interaction of c-Raf....

  12. Rock Physical Interpretation of the Relationship between Dynamic and Static Young's Moduli of Sedimentary Rocks

    Science.gov (United States)

    Takahashi, T.

    2017-12-01

    The static Young's modulus (deformability) of a rock is indispensable for designing and constructing tunnels, dams and underground caverns in civil engineering. Static Young's modulus which is an elastic modulus at large strain level is usually obtained with the laboratory tests of rock cores sampled in boreholes drilled in a rock mass. A deformability model of the entire rock mass is then built by extrapolating the measurements based on a rock mass classification obtained in geological site characterization. However, model-building using data obtained from a limited number of boreholes in the rock mass, especially a complex rock mass, may cause problems in the accuracy and reliability of the model. On the other hand, dynamic Young's modulus which is the modulus at small strain level can be obtained from seismic velocity. If dynamic Young's modulus can be rationally converted to static one, a seismic velocity model by the seismic method can be effectively used to build a deformability model of the rock mass. In this study, we have, therefore, developed a rock physics model (Mavko et al., 2009) to estimate static Young's modulus from dynamic one for sedimentary rocks. The rock physics model has been generally applied to seismic properties at small strain level. In the proposed model, however, the sandy shale model, one of rock physics models, is extended for modeling the static Young's modulus at large strain level by incorporating the mixture of frictional and frictionless grain contacts into the Hertz-Mindlin model. The proposed model is verified through its application to the dynamic Young's moduli derived from well log velocities and static Young's moduli measured in the tri-axial compression tests of rock cores sampled in the same borehole as the logs were acquired. This application proves that the proposed rock physics model can be possibly used to estimate static Young's modulus (deformability) which is required in many types of civil engineering applications

  13. The Roles of Protein Kinases in Learning and Memory

    Science.gov (United States)

    Giese, Karl Peter; Mizuno, Keiko

    2013-01-01

    In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate…

  14. Increased rho kinase activity in mononuclear cells of dialysis and stage 3-4 chronic kidney disease patients with left ventricular hypertrophy: Cardiovascular risk implications.

    Science.gov (United States)

    Calò, Lorenzo A; Vertolli, Ugo; Pagnin, Elisa; Ravarotto, Verdiana; Davis, Paul A; Lupia, Mario; Naso, Elena; Maiolino, Giuseppe; Naso, Agostino

    2016-03-01

    Cardiovascular disease (CVD) is the leading cause of excess mortality in chronic kidney disease (CKD) and dialysis patients (DP) who have higher prevalence of left ventricular hypertrophy (LVH), the strongest predictor of CV events. Rho kinase (ROCK) activation is linked in hypertensive patients to cardiac remodeling while ROCK inhibition suppresses cardiomyocyte hypertrophy and, in a human clinical condition opposite to hypertension, its downregulation associates with lack of CV remodeling. Information on ROCK activation-LVH link in CKD and DP is lacking. Mononuclear cells (PBMCs) MYPT-1 phosphorylation, a marker of ROCK activity, and the effect of fasudil, a ROCK inhibitor, on MYPT-1 phosphorylation were assessed in 23 DPs, 13 stage 3-4 CKD and 36 healthy subjects (HS) by Western blot. LV mass was assessed by M-mode echocardiography. DP and CKD had higher MYPT-1 phosphorylation compared to HS (p<0.001 and p=0.003). Fasudil (500 and 1000μM) dose dependently reduced MYPT-1 phosphorylation in DP (p<0.01). DP had higher LV mass than CKD (p<0.001). MYPT-1 phosphorylation was higher in patients with LVH (p=0.009) and correlated with LV mass both in DP and CKD with LVH (p<0.001 and p=0.006). In DP and CKD, ROCK activity tracks with LVH. This ROCK activation-LVH link provided in these CVD high-risk patients along with similar findings in hypertensive patients and added to opposite findings in a human model opposite to hypertension and in type 2 diabetic patients, identify ROCK activation as a potential LVH marker and provide further rationale for ROCK activation inhibition as target of therapy in CVD high-risk patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Dynamic elastic moduli of rocks under pressure

    Energy Technology Data Exchange (ETDEWEB)

    Schock, R N [Lawrence Radiation Laboratory, University of California, Livermore, CA (United States)

    1970-05-01

    Elastic moduli are determined as a function of confining pressure to 10 kb on rocks in which Plowshare shots are to be fired. Numerical simulation codes require accurate information on the mechanical response of the rock medium to various stress levels in order to predict cavity dimensions. The theoretical treatment of small strains in an elastic medium relates the propagation velocity of compressional and shear waves to the elastic moduli. Velocity measurements can provide, as unique code input data, the rigidity modulus, Poisson' ratio and the shear wave velocity, as well as providing checks on independent determinations of the other moduli. Velocities are determined using pulsed electro-mechanical transducers and measuring the time-of-flight in the rock specimen. A resonant frequency of 1 MHz is used to insure that the wavelength exceeds the average grain dimension and is subject to bulk rock properties. Data obtained on a variety of rock types are presented and analyzed. These data are discussed in terms of their relationship to moduli measured by static methods as well as the effect of anisotropy, porosity, and fractures. In general, fractured rocks with incipient cracks show large increases in velocity and moduli in the first 1 to 2 kb of compression as a result of the closing of these voids. After this, the velocities increase much more slowly. Dynamic moduli for these rocks are often 10% higher than corresponding static moduli at low pressure, but this difference decreases as the voids are closed until the moduli agree within experimental error. The discrepancy at low pressure is a result of the elastic energy in the wave pulse being propagated around cracks, with little effect on propagation velocity averaged over the entire specimen. (author)

  16. Compact rock material gas permeability properties

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huanling, E-mail: whl_hm@163.com [Key Laboratory of Coastal Disaster and Defence, Ministry of Education, Hohai University, Nanjing 210098 (China); LML, University of Lille, Cite Scientifique, 59655 Villeneuve d’Ascq (France); Xu, Weiya; Zuo, Jing [Institutes of Geotechnical Engineering, Hohai University, Nanjing 210098 (China)

    2014-09-15

    Natural compact rocks, such as sandstone, granite, and rock salt, are the main materials and geological environment for storing underground oil, gas, CO{sub 2,} shale gas, and radioactive waste because they have extremely low permeabilities and high mechanical strengths. Using the inert gas argon as the fluid medium, the stress-dependent permeability and porosity of monzonitic granite and granite gneiss from an underground oil storage depot were measured using a permeability and porosity measurement system. Based on the test results, models for describing the relationships among the permeability, porosity, and confining pressure of rock specimens were analyzed and are discussed. A power law is suggested to describe the relationship between the stress-dependent porosity and permeability; for the monzonitic granite and granite gneiss (for monzonitic granite (A-2), the initial porosity is approximately 4.05%, and the permeability is approximately 10{sup −19} m{sup 2}; for the granite gneiss (B-2), the initial porosity is approximately 7.09%, the permeability is approximately 10{sup −17} m{sup 2}; and the porosity-sensitivity exponents that link porosity and permeability are 0.98 and 3.11, respectively). Compared with moderate-porosity and high-porosity rocks, for which φ > 15%, low-porosity rock permeability has a relatively lower sensitivity to stress, but the porosity is more sensitive to stress, and different types of rocks show similar trends. From the test results, it can be inferred that the test rock specimens’ permeability evolution is related to the relative particle movements and microcrack closure.

  17. Measurement of diffusive properties of intact rock

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, K B

    1996-12-01

    In the Postclosure Assessment of a Reference System for the Disposal of Canada`s Nuclear Fuel Waste (Goodwin et al. 1994) the disposal vault is assumed to be surrounded by a zone of intact rock, referred to as the `exclusion zone.` A sensitivity analysis of the relative effectiveness of the several engineered and natural barriers that contribute to the safety of the reference disposal system has shown that this zone of intact rock is the most effective of these barriers to the movement of radionuclides through the reference system. Peer review of the geosphere model used in the case study for the EIS (Environmental Impact Statement) of the Canadian Nuclear Fuel Waste Management Program has identified the need to quantify the properties of the intact rock surrounding the disposal vault that would control the transport of radionuclides by diffusion. The Postclosure Assessment also identified the need for appropriate values of the free water diffusion coefficient (D{sub o}) for {sup 129}1 and {sup 14}C. The measurement of rock resistivity allows the calculation of the Formation Factor for a rock This review describes the Formation Factor, diffusivity, permeability, and porosity, and how these properties might be measured or inferred for insitu rock under the conditions that apply to the intact rock surrounding a potential disposal vault. The importance of measuring the intrinsic diffusion coefficient (D{sup i}) of diffusing species under solution salinities simulating those of groundwaters is emphasised, and a method of measurement is described that is independent of the diffusing medium, and which would be appropriate for measurements made in chemically complex media such as groundwaters. (author). 95 refs., 4 tabs., 39 figs.

  18. Dynamic elastic moduli of rocks under pressure

    International Nuclear Information System (INIS)

    Schock, R.N.

    1970-01-01

    Elastic moduli are determined as a function of confining pressure to 10 kb on rocks in which Plowshare shots are to be fired. Numerical simulation codes require accurate information on the mechanical response of the rock medium to various stress levels in order to predict cavity dimensions. The theoretical treatment of small strains in an elastic medium relates the propagation velocity of compressional and shear waves to the elastic moduli. Velocity measurements can provide, as unique code input data, the rigidity modulus, Poisson' ratio and the shear wave velocity, as well as providing checks on independent determinations of the other moduli. Velocities are determined using pulsed electro-mechanical transducers and measuring the time-of-flight in the rock specimen. A resonant frequency of 1 MHz is used to insure that the wavelength exceeds the average grain dimension and is subject to bulk rock properties. Data obtained on a variety of rock types are presented and analyzed. These data are discussed in terms of their relationship to moduli measured by static methods as well as the effect of anisotropy, porosity, and fractures. In general, fractured rocks with incipient cracks show large increases in velocity and moduli in the first 1 to 2 kb of compression as a result of the closing of these voids. After this, the velocities increase much more slowly. Dynamic moduli for these rocks are often 10% higher than corresponding static moduli at low pressure, but this difference decreases as the voids are closed until the moduli agree within experimental error. The discrepancy at low pressure is a result of the elastic energy in the wave pulse being propagated around cracks, with little effect on propagation velocity averaged over the entire specimen. (author)

  19. Measurement of diffusive properties of intact rock

    International Nuclear Information System (INIS)

    Harvey, K.B.

    1996-12-01

    In the Postclosure Assessment of a Reference System for the Disposal of Canada's Nuclear Fuel Waste (Goodwin et al. 1994) the disposal vault is assumed to be surrounded by a zone of intact rock, referred to as the 'exclusion zone.' A sensitivity analysis of the relative effectiveness of the several engineered and natural barriers that contribute to the safety of the reference disposal system has shown that this zone of intact rock is the most effective of these barriers to the movement of radionuclides through the reference system. Peer review of the geosphere model used in the case study for the EIS (Environmental Impact Statement) of the Canadian Nuclear Fuel Waste Management Program has identified the need to quantify the properties of the intact rock surrounding the disposal vault that would control the transport of radionuclides by diffusion. The Postclosure Assessment also identified the need for appropriate values of the free water diffusion coefficient (D o ) for 129 1 and 14 C. The measurement of rock resistivity allows the calculation of the Formation Factor for a rock This review describes the Formation Factor, diffusivity, permeability, and porosity, and how these properties might be measured or inferred for insitu rock under the conditions that apply to the intact rock surrounding a potential disposal vault. The importance of measuring the intrinsic diffusion coefficient (D i ) of diffusing species under solution salinities simulating those of groundwaters is emphasised, and a method of measurement is described that is independent of the diffusing medium, and which would be appropriate for measurements made in chemically complex media such as groundwaters. (author). 95 refs., 4 tabs., 39 figs

  20. Abraded Target on Rock 'Champagne' in Gusev Crater

    Science.gov (United States)

    2005-01-01

    NASA's Mars Exploration Rover Spirit took this microscopic image of a target called 'Bubbles' on a rock called 'Champagne' after using its rock abrasion tool to grind a hole through the rock's outer surface. The circular area where the rock's interior is exposed is about 5 centimeters (2 inches) across. This rock is different from rocks out on the plains of Gusev Crater but is similar to other rocks in this area of the 'Columbia Hills' in that it rich in phosphorus. Plagioclase, a mineral commonly found in igneous rocks, is also present in these rocks, according to analysis with Spirit's miniature thermal emission spectrometer. By using the rover's alpha particle X-ray spectrometer to collect data for multiple martian days, or sols, scientists are also beginning to get measurements of trace elements in the rocks. Spirit took the images that are combined into this mosaic on sol 358 (Jan. 3, 2005).

  1. Design of Aminobenzothiazole Inhibitors of Rho Kinases 1 and 2 by Using Protein Kinase A as a Structure Surrogate.

    Science.gov (United States)

    Judge, Russell A; Vasudevan, Anil; Scott, Victoria E; Simler, Gricelda H; Pratt, Steve D; Namovic, Marian T; Putman, C Brent; Aguirre, Ana; Stoll, Vincent S; Mamo, Mulugeta; Swann, Steven I; Cassar, Steven C; Faltynek, Connie R; Kage, Karen L; Boyce-Rustay, Janel M; Hobson, Adrian D

    2018-03-16

    We describe the design, synthesis, and structure-activity relationships (SARs) of a series of 2-aminobenzothiazole inhibitors of Rho kinases (ROCKs) 1 and 2, which were optimized to low nanomolar potencies by use of protein kinase A (PKA) as a structure surrogate to guide compound design. A subset of these molecules also showed robust activity in a cell-based myosin phosphatase assay and in a mechanical hyperalgesia in vivo pain model. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Kinase impact assessment in the landscape of fusion genes that retain kinase domains: a pan-cancer study

    Science.gov (United States)

    Kim, Pora; Jia, Peilin; Zhao, Zhongming

    2018-01-01

    Abstract Assessing the impact of kinase in gene fusion is essential for both identifying driver fusion genes (FGs) and developing molecular targeted therapies. Kinase domain retention is a crucial factor in kinase fusion genes (KFGs), but such a systematic investigation has not been done yet. To this end, we analyzed kinase domain retention (KDR) status in chimeric protein sequences of 914 KFGs covering 312 kinases across 13 major cancer types. Based on 171 kinase domain-retained KFGs including 101 kinases, we studied their recurrence, kinase groups, fusion partners, exon-based expression depth, short DNA motifs around the break points and networks. Our results, such as more KDR than 5′-kinase fusion genes, combinatorial effects between 3′-KDR kinases and their 5′-partners and a signal transduction-specific DNA sequence motif in the break point intronic sequences, supported positive selection on 3′-kinase fusion genes in cancer. We introduced a degree-of-frequency (DoF) score to measure the possible number of KFGs of a kinase. Interestingly, kinases with high DoF scores tended to undergo strong gene expression alteration at the break points. Furthermore, our KDR gene fusion network analysis revealed six of the seven kinases with the highest DoF scores (ALK, BRAF, MET, NTRK1, NTRK3 and RET) were all observed in thyroid carcinoma. Finally, we summarized common features of ‘effective’ (highly recurrent) kinases in gene fusions such as expression alteration at break point, redundant usage in multiple cancer types and 3′-location tendency. Collectively, our findings are useful for prioritizing driver kinases and FGs and provided insights into KFGs’ clinical implications. PMID:28013235

  3. Underground Research Laboratories for Crystalline Rock and Sedimentary Rock in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Shigeta, N.; Takeda, S.; Matsui, H.; Yamasaki, S.

    2003-02-27

    The Japan Nuclear Cycle Development Institute (JNC) has started two off-site (generic) underground research laboratory (URL) projects, one for crystalline rock as a fractured media and the other for sedimentary rock as a porous media. This paper introduces an overview and current status of these projects.

  4. Evaluation of the layering of rock strata and basement rock depth of ...

    African Journals Online (AJOL)

    The layering of rock strata and depth to the basement rocks of a Federal University Teaching Hospital premises in Northern Nigeria was investigated in this study with the aim of providing 2D geo-electrical resistivity images of the subsurface for geotechnical development using a modern and state-of-the-art field instrument, ...

  5. Cecal bacterial communities in wild Japanese rock ptarmigans and captive Svalbard rock ptarmigans.

    Science.gov (United States)

    Ushida, Kazunari; Segawa, Takahiro; Tsuchida, Sayaka; Murata, Koichi

    2016-02-01

    Preservation of indigenous gastrointestinal microbiota is deemed to be critical for successful captive breeding of endangered wild animals, yet its biology is poorly understood. Here, we investigated cecal bacterial communities in wild Japanese rock ptarmigans (Lagopus muta japonica) and compared them with those in Svalbard rock ptarmigans (L. m. hyperborea) in captivity. Ultra-deep sequencing of 16S rRNA gene indicated that the community structure of cecal microbiota in wild rock ptarmigans was remarkably different from that in captive Svalbard rock ptarmigans. Fundamental differences between bacterial communities in the two groups of birds were detected at the phylum level. Firmicutes, Actinobacteria, Bacteroidetes and Synergistetes were the major phyla detected in wild Japanese rock ptarmigans, whereas Firmicutes alone occupied more than 80% of abundance in captive Svalbard rock ptarmigans. Furthermore, unclassified genera of Coriobacteriaceae, Synergistaceae, Bacteroidaceae, Actinomycetaceae, Veillonellaceae and Clostridiales were the major taxa detected in wild individuals, whereas in zoo-reared birds, major genera were Ruminococcus, Blautia, Faecalibacterium and Akkermansia. Zoo-reared birds seemed to lack almost all rock ptarmigan-specific bacteria in their intestine, which may explain the relatively high rate of pathogenic infections affecting them. We show evidence that preservation and reconstitution of indigenous cecal microflora are critical for successful ex situ conservation and future re-introduction plan for the Japanese rock ptarmigan.

  6. THM-coupled modeling of selected processes in argillaceous rock relevant to rock mechanics

    International Nuclear Information System (INIS)

    Czaikowski, Oliver

    2012-01-01

    Scientific investigations in European countries other than Germany concentrate not only on granite formations (Switzerland, Sweden) but also on argillaceous rock formations (France, Switzerland, Belgium) to assess their suitability as host and barrier rock for the final storage of radioactive waste. In Germany, rock salt has been under thorough study as a host rock over the past few decades. According to a study by the German Federal Institute for Geosciences and Natural Resources, however, not only salt deposits but also argillaceous rock deposits are available at relevant depths and of extensions in space which make final storage of high-level radioactive waste basically possible in Germany. Equally qualified findings about the suitability/unsuitability of non-saline rock formations require fundamental studies to be conducted nationally because of the comparatively low level of knowledge. The article presents basic analyses of coupled mechanical and hydraulic properties of argillaceous rock formations as host rock for a repository. The interaction of various processes is explained on the basis of knowledge derived from laboratory studies, and open problems are deduced. For modeling coupled processes, a simplified analytical computation method is proposed and compared with the results of numerical simulations, and the limits to its application are outlined. (orig.)

  7. Strength Assessment of Broken Rock Postgrouting Reinforcement Based on Initial Broken Rock Quality and Grouting Quality

    Directory of Open Access Journals (Sweden)

    Hongfa Xu

    2017-01-01

    Full Text Available To estimate postgrouting rock mass strength growth is important for engineering design. In this paper, using self-developed indoor pressure-grouting devices, 19 groups of test cubic blocks were made of the different water cement ratio grouting into the broken rock of three kinds of particle sizes. The shear strength parameters of each group under different conditions were tested. Then this paper presents a quantitative calculation method for predicting the strength growth of grouted broken rock. Relational equations were developed to investigate the relationship between the growth rates of uniaxial compressive strength (UCS, absolute value of uniaxial tensile strength (AUTS, internal friction angle, and cohesion for post- to pregrouting broken rock based on Mohr-Coulomb strength criterion. From previous test data, the empirical equation between the growth rate of UCS and the ratio of the initial rock mass UCS to the grout concretion UCS has been determined. The equations of the growth rates of the internal friction coefficient and UCS for grouting broken rock with rock mass rating (RMR and its increment have been established. The calculated results are consistent with the experimental results. These observations are important for engineered design of grouting reinforcement for broken rock mass.

  8. Inhibitory effect of rhynchophylline on contraction of cerebral arterioles to endothelin 1: role of rho kinase.

    Science.gov (United States)

    Hao, Hui-Feng; Liu, Li-Mei; Liu, Yu-Ying; Liu, Juan; Yan, Li; Pan, Chun-Shui; Wang, Ming-Xia; Wang, Chuan-She; Fan, Jing-Yu; Gao, Yuan-Sheng; Han, Jing-Yan

    2014-08-08

    Rhynchophylline (Rhy) is a major ingredient of Uncaria rhynchophylla (UR) used to reduce blood pressure and ameliorate brain ailments. This study was to examine the role of Rho kinase (ROCK) in the inhibition of Rhy on contraction of cerebral arterioles caused by endothelin 1 (ET-1). Cerebral arterioles of male Wistar rats were constricted with ET-1 for 10 min followed by perfusion of Rhy for 20 min. Changes in the diameters of the arterioles were recorded. The effects of Rhy on contraction of middle cerebral arteries (MCAs) were determined by a Multi-Myograph. Western blotting and immunofluorescent staining were used to examine the effects of Rhy on RhoA translocation and myosin phosphatase target subunit 1 (MYPT1) phosphorylation. In vivo, Rhy (30-300 µM) relaxed cerebral arterioles constricted with ET-1 dose-dependently. In vitro, Rhy at lower concentrations (1-100 µM) caused relaxation of rat MCAs constricted with KCl and Bay-K8644 (an agonist of L-type voltage-dependent calcium channels (L-VDCCs)). Rhy at higher concentrations (>100 µM) caused relaxation of rat MCAs constricted with ET-1, which was inhibited by Y27632, a ROCK׳s inhibitor. Western blotting of rat aortas showed that Rhy inhibited RhoA translocation and MYPT1 phosphorylation. Immunofluorescent staining of MCAs confirmed that phosphorylation of MYPT1 caused by ET-1 was inhibited by Rhy. These results demonstrate that Rhy is a potent inhibitor of contraction of cerebral arteries caused by ET-1 in vivo and in vitro. The effect of Rhy was in part mediated by inhibiting RhoA-ROCK signaling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Nitrogen in rock: Occurrences and biogeochemical implications

    Science.gov (United States)

    Holloway, J.M.; Dahlgren, R.A.

    2002-01-01

    There is a growing interest in the role of bedrock in global nitrogen cycling and potential for increased ecosystem sensitivity to human impacts in terrains with elevated background nitrogen concentrations. Nitrogen-bearing rocks are globally distributed and comprise a potentially large pool of nitrogen in nutrient cycling that is frequently neglected because of a lack of routine analytical methods for quantification. Nitrogen in rock originates as organically bound nitrogen associated with sediment, or in thermal waters representing a mixture of sedimentary, mantle, and meteoric sources of nitrogen. Rock nitrogen concentrations range from trace levels (>200 mg N kg -1) in granites to ecologically significant concentrations exceeding 1000 mg N kg -1 in some sedimentary and metasedimentary rocks. Nitrate deposits accumulated in arid and semi-arid regions are also a large potential pool. Nitrogen in rock has a potentially significant impact on localized nitrogen cycles. Elevated nitrogen concentrations in water and soil have been attributed to weathering of bedrock nitrogen. In some environments, nitrogen released from bedrock may contribute to nitrogen saturation of terrestrial ecosystems (more nitrogen available than required by biota). Nitrogen saturation results in leaching of nitrate to surface and groundwaters, and, where soils are formed from ammonium-rich bedrock, the oxidation of ammonium to nitrate may result in soil acidification, inhibiting revegetation in certain ecosystems. Collectively, studies presented in this article reveal that geologic nitrogen may be a large and reactive pool with potential for amplification of human impacts on nitrogen cycling in terrestrial and aquatic ecosystems.

  10. Rock Directed Breaking Under the Impulse Load

    Science.gov (United States)

    Khomeriki, Sergo; Mataradze, Edgar; Chikhradze, Nikoloz; Losaberidze, Marine; Khomeriki, Davit; Shatberashvili, Grigol

    2016-10-01

    In the work the problem of directed chipping of facing stone material by means of managing of explosion process is considered. The technology of the mining of decorative stone by the use of explosion energy means the very rapid transfer of potential energy of elastic deformations to kinetic energy. As a result, the explosion impulse, in the expanse of the inertia of rock massive, does not cause the increase of existing cracks. In the course of explosion, the shock wave is propagated by ultrasonic velocity and in this case the medium parameters (pressure, density, temperature, velocity) increase in spurts. In spite of this fact the all three conservation laws of mechanics remain valid on basis of three laws the equations are derived by which the parameters of shock wave may be defined by means of the rock physical-mechanical properties. The load on the body volume at breaking under explosion acts over very small period of the time. Therefore, stressed-deformed state of the rock was studied when the impulse load acts on the boundary. It was considered that the mining of the blocks of facing stone is performed from the hard rocks. This means that the breaking proceeds in the zone of elastic deformation. In the conditions of mentioned assumptions, the expression of the stress tensor and displacement of vector components initiated by stressed-deformed state in the rock are written.

  11. Phosphate rock costs, prices and resources interaction.

    Science.gov (United States)

    Mew, M C

    2016-01-15

    This article gives the author's views and opinions as someone who has spent his working life analyzing the international phosphate sector as an independent consultant. His career spanned two price hike events in the mid-1970's and in 2008, both of which sparked considerable popular and academic interest concerning adequacy of phosphate rock resources, the impact of rising mining costs and the ability of mankind to feed future populations. An analysis of phosphate rock production costs derived from two major industry studies performed in 1983 and 2013 shows that in nominal terms, global average cash production costs increased by 27% to $38 per tonne fob mine in the 30 year period. In real terms, the global average cost of production has fallen. Despite the lack of upward pressure from increasing costs, phosphate rock market prices have shown two major spikes in the 30 years to 2013, with periods of less volatility in between. These price spike events can be seen to be related to the escalating investment cost required by new mine capacity, and as such can be expected to be repeated in future. As such, phosphate rock price volatility is likely to have more impact on food prices than rising phosphate rock production costs. However, as mining costs rise, recycling of P will also become increasingly driven by economics rather than legislation. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Transient evoked otoacoustic emissions in rock musicians.

    Science.gov (United States)

    Høydal, Erik Harry; Lein Størmer, Carl Christian; Laukli, Einar; Stenklev, Niels Christian

    2017-09-01

    Our focus in this study was the assessment of transient evoked otoacoustic emissions (TEOAEs) in a large group of rock musicians. A further objective was to analyse tinnitus among rock musicians as related to TEOAEs. The study was a cross-sectional survey of rock musicians selected at random. A control group was included at random for comparison. We recruited 111 musicians and a control group of 40 non-musicians. Testing was conducted by using clinical examination, pure tone audiometry, TEOAEs and a questionnaire. TEOAE SNR in the half-octave frequency band centred on 4 kHz was significantly lower bilaterally in musicians than controls. This effect was strongly predicted by age and pure-tone hearing threshold levels in the 3-6 kHz range. Bilateral hearing thresholds were significantly higher at 6 kHz in musicians. Twenty percent of the musicians had permanent tinnitus. There was no association between the TEOAE parameters and permanent tinnitus. Our results suggest an incipient hearing loss at 6 kHz in rock musicians. Loss of TEOAE SNR in the 4 kHz half-octave frequency band was observed, but it was related to higher mean 3-6 kHz hearing thresholds and age. A large proportion of rock musicians have permanent tinnitus.

  13. Footwear in rock climbing: Current practice.

    Science.gov (United States)

    McHenry, R D; Arnold, G P; Wang, W; Abboud, R J

    2015-09-01

    Many rock climbers wear ill-fitting and excessively tight footwear during activity. However, there is insufficient evidence of the extent or harms of this practice. To investigate footwear use in rock climbers with a focus on issues surrounding fit. A cross-sectional study with active rock climbers of over one year of experience completing a survey on their activity and footwear. Additionally, the authors quantified foot and shoe lengths and sizes alongside demographic data. Ill-fitting and excessively tight footwear was found in 55 out of 56 rock climbers. Foot pain during activity was also commonplace in 91% of the climbers. A mean size reduction of almost 4 UK shoe sizes was found between the climbers' street shoe size and that of their climbing footwear using a calibrated foot/shoe ruler. There is an unfortunate association of climbers of higher abilities seeking a tighter shoe fit (pfootwear use amongst rock climbers, further investigation may aim to quantify its impact and seek a solution balancing climbing performance while mitigating foot injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Transport of suspended matter through rock formations

    International Nuclear Information System (INIS)

    Wahlig, B.G.

    1980-01-01

    It may be hypothesized that significant quantities of some waste nuclides could be adsorbed on the surfaces of particles suspended in the flowing groundwater and thereby migrate farther or faster than they would in dissolved form. This thesis deals with one aspect of this proposed migration mechanism, the transport of suspended matter through rock formations. A theoretical examination of the forces effecting suspended particles in flowing groundwater indicates that only two interaction energies are likely to be significant compared to the particles' thermal energies. The responsible interactions are van der Waals attraction between the particles and the rock, and electrolytic double-layer repulsion between the atmospheres of ions near the surfaces of the particles and the rock. This theoretical understanding was tested in column flow adsorption experiments using fine kaolin particles as the suspended matter and crushed basalt as the rock medium. The effects of several parameters on kaolin mobility were explored, including the influences of the following: solution ion concentration, solution cation valence, degree of solution oxygen saturation, solution flow velocity, and degree of rock surface ageing. The experimental results indicate that the migration of suspended matter over kilometer distances in the lithosphere is very unlikely unless the average pore size of the conducting mediumis fairly large (> 1mm), or the flow occurs in large fractures

  15. Rock stress measurements in the Grimsel Underground Rock Laboratory and their geological interpretation

    International Nuclear Information System (INIS)

    Braeuer, V.; Heusermann, S.; Pahl, A.

    1989-01-01

    Rock stress is being studied as part of the Swiss-German cooperation between the National Cooperative for the Storage of Radioactive Waste (NAGRA), the Research Centre for Environmental Sciences (GSF), and the Federal Institute for Geosciences and Natural Resources (BGR) in the Grimsel Rock Laboratory in Switzerland. Several methods and various equipment for measuring rock stress have been developed and tested in an approximately 200-m borehole drilled from a gallery at a depth of 450 m. The measurements were made continually during overcoring; the data were recorded and processed in a computer located downhole or outside the borehole. The results of the overcoring tests and of frac tests indicate a principle horizontal stress of 25-40 MPa, directed mainly NW-SE. Detailed geological mapping shows relationships between stress and rock structure. A zone of nearly unfractured rock exhibits an increase in stress and a change in stress direction. (orig.)

  16. The analysis of creep characteristics of the surrounding rock of the carbonaceous rock tunnel based on Singh-Mitchell model

    Science.gov (United States)

    Luo, Junhui; Mi, Decai; Ye, Qiongyao; Deng, Shengqiang; Zeng, Fuquan; Zeng, Yongjun

    2018-01-01

    Carbonaceous rock has the characteristics of easy disintegration, softening, swelling and environmental sensitivity, which belongs to soft surrounding rock, and the deformation during excavation and long-term stability of the surrounding rock of carbonaceous rock tunnel are common problems in the construction of carbonaceous rock tunnel. According to the above, the Monitor and measure the displacement, temperature and osmotic pressure of the surrounding carbonaceous rock of the tunnel of Guangxi Hebai highway. Then it based on the obtaining data to study the creep mechanism of surrounding rock using Singh-Mitchell model and predict the deformation of surrounding rock before the tunnel is operation. The results show that the Singh-Mitchell creep model can effectively analyse and predict the deformation development law of surrounding rock of tunnel without considering temperature and osmotic pressure, it can provide reference for the construction of carbonaceous rock tunnel and the measures to prevent and reinforce it..

  17. Roles of Apicomplexan protein kinases at each life cycle stage.

    Science.gov (United States)

    Kato, Kentaro; Sugi, Tatsuki; Iwanaga, Tatsuya

    2012-06-01

    Inhibitors of cellular protein kinases have been reported to inhibit the development of Apicomplexan parasites, suggesting that the functions of protozoan protein kinases are critical for their life cycle. However, the specific roles of these protein kinases cannot be determined using only these inhibitors without molecular analysis, including gene disruption. In this report, we describe the functions of Apicomplexan protein kinases in each parasite life stage and the potential of pre-existing protein kinase inhibitors as Apicomplexan drugs against, mainly, Plasmodium and Toxoplasma. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling.

    Science.gov (United States)

    Nyati, Shyam; Schinske-Sebolt, Katrina; Pitchiaya, Sethuramasundaram; Chekhovskiy, Katerina; Chator, Areeb; Chaudhry, Nauman; Dosch, Joseph; Van Dort, Marcian E; Varambally, Sooryanarayana; Kumar-Sinha, Chandan; Nyati, Mukesh Kumar; Ray, Dipankar; Walter, Nils G; Yu, Hongtao; Ross, Brian Dale; Rehemtulla, Alnawaz

    2015-01-06

    Transforming growth factor-β (TGF-β) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-β, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF-β signaling. BUB1 interacted with TGFBRI in the presence of TGF-β and promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1 interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD-dependent transcription, and TGF-β-mediated changes in cellular phenotype including epithelial-mesenchymal transition (EMT), migration, and invasion. Knockdown of BUB1 also impaired noncanonical TGF-β signaling mediated by the kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1 to promote TGF-β signaling depended on the kinase activity of BUB1. A small-molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase-deficient mutant of BUB1 suppressed TGF-β signaling and formation of the ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase in the TGF-β pathway in a role beyond its established function in cell cycle regulation and chromosome cohesion. Copyright © 2015, American Association for the Advancement of Science.

  19. Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase*S⃞

    Science.gov (United States)

    Kang, Nam Joo; Lee, Ki Won; Lee, Dong Eun; Rogozin, Evgeny A.; Bode, Ann M.; Lee, Hyong Joo; Dong, Zigang

    2008-01-01

    Cocoa was shown to inhibit chemically induced carcinogenesis in animals and exert antioxidant activity in humans. However, the molecular mechanisms of the chemopreventive potential of cocoa and its active ingredient(s) remain unknown. Here we report that cocoa procyanidins inhibit neoplastic cell transformation by suppressing the kinase activity of mitogen-activated protein kinase kinase (MEK). A cocoa procyanidin fraction (CPF) and procyanidin B2 at 5 μg/ml and 40 μm, respectively, inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ mouse epidermal (JB6 P+) cells by 47 and 93%, respectively. The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-κB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2. In vitro and ex vivo kinase assay data demonstrated that CPF or procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation. In contrast, theobromine (up to 80 μm) had no effect on TPA-induced transformation, cyclooxygenase-2 expression, the transactivation of activator protein-1 or nuclear factor-κB, or MEK. Notably, procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity and neoplastic cell transformation. PMID:18519570

  20. Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

    Science.gov (United States)

    Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

    2011-02-10

    Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.

  1. Fractal Analysis of Rock Joint Profiles

    Science.gov (United States)

    Audy, Ondřej; Ficker, Tomáš

    2017-10-01

    Surface reliefs of rock joints are analyzed in geotechnics when shear strength of rocky slopes is estimated. The rock joint profiles actually are self-affine fractal curves and computations of their fractal dimensions require special methods. Many papers devoted to the fractal properties of these profiles were published in the past but only a few of those papers employed a convenient computational method that would have guaranteed a sound value of that dimension. As a consequence, anomalously low dimensions were presented. This contribution deals with two computational modifications that lead to sound fractal dimensions of the self-affine rock joint profiles. These are the modified box-counting method and the modified yard-stick method sometimes called the compass method. Both these methods are frequently applied to self-similar fractal curves but the self-affine profile curves due to their self-affine nature require modified computational procedures implemented in computer programs.

  2. Do Bare Rocks Exist on the Moon?

    Science.gov (United States)

    Allen, Carlton; Bandfield, Joshua; Greenhagen, Benjamin; Hayne, Paul; Leader, Frank; Paige, David

    2017-01-01

    Astronaut surface observations and close-up images at the Apollo and Chang'e 1 landing sites confirm that at least some lunar rocks have no discernable dust cover. However, ALSEP (Apollo Lunar Surface Experiments Package) measurements as well as astronaut and LADEE (Lunar Atmosphere and Dust Environment Explorer) orbital observations and laboratory experiments possibly suggest that a fine fraction of dust is levitated and moves across and above the lunar surface. Over millions of years such dust might be expected to coat all exposed rock surfaces. This study uses thermal modeling, combined with Diviner (a Lunar Reconnaissance Orbiter experiment) orbital lunar eclipse temperature data, to further document the existence of bare rocks on the lunar surface.

  3. Aespoe Hard Rock Laboratory. Annual Report 1993

    International Nuclear Information System (INIS)

    1994-06-01

    The Aespoe Hard Rock Laboratory is being constructed in preparation for the deep geological repository of spent fuel in Sweden. This Annual Report 1993 for the Aespoe Hard Rock Laboratory contains an overview of the work conducted. Present work is focused on verification of pre-investigation methods and development of the detailed investigation methodology. Construction of the facility and investigation of the bedrock are carried out in parallel. As of December 1993, 2760 m of the tunnel had been excavated to a depth of 370 m below the surface. An important and integral part of the work is further refinement of conceptual and numerical models for groundwater flow and radionuclide migration. Detailed plans have been prepared for several experiments to be conducted after the end of the construction work. Eight organizations from seven countries are now participating in the work at the Aespoe Hard Rock Laboratory and are contributing in different ways to the results being achieved

  4. Structure analysis - chiromancy of the rock

    International Nuclear Information System (INIS)

    Huber, A.; Huber, M.

    1989-01-01

    The reader may initially be surprised by a comparison between structure analysis and palmistry which is, in effect, a comparison between a scientific research method on the one hand and art which is equated with magical powers on the other. In the figurative sense, however, these two fields have some points in common which should help us to obtain a first impression of the nature of geological structure analysis. Chiromancy uses the lines and the form of the hand to predict the character and the future of the person in question. In the same way, geologists use rocks and rock forms to obtain information on structure and behaviour of different formations. Structure analysis is a specialised field of geological investigation in which traces of deformation are interpreted as expressions of rockforming forces. This article discusses how and why the character of a rock formation as well as its past, present and even future behaviour can be determined using structure analysis. (author) 11 figs

  5. Continuous distillation of oil-bearing rocks

    Energy Technology Data Exchange (ETDEWEB)

    1923-11-14

    A continuous process of distilling petroleum-bearing, asphaltic, or bituminous rocks to free bitumen is characterized by vaporizing hydrocarbons solid, pasty, or liquid from petroleum-containing asphaltic or bituminous rocks to free bitumen without ever reaching the temperatures at which they can produce decomposition, the necessary heat being furnished by combustion of part of the hydrocarbons of the treated rocks. A furnace for carrying out the process of claim 1 is characterized by consisting of a cavity lined inside with reflector, of variable section and with a throat at the upper part for charging the material to be treated and means for blowing the lower part of the furnace with the air necessary for combustion and inert gas for regulating the combustion and removal of the hydrocarbons.

  6. Effects of atmospheric moisture on rock resistivity.

    Science.gov (United States)

    Alvarez, R.

    1973-01-01

    This study examines the changes in resistivity of rock samples as induced by atmospheric moisture. Experiments were performed on samples of hematitic sandstone, pyrite, and galena. The sandstone underwent a change in resistivity of four orders of magnitude when it was measured in a vacuum of 500 ntorr and in air of 37% relative humidity. Pyrite and galena showed no variations in resistivity when they were measured under the same conditions. These results, plus others obtained elsewhere, indicate that rocks of the resistive type are affected in their electrical properties by atmospheric moisture, whereas rocks of the conductive type are not. The experimental evidence obtained is difficult to reconcile with a model of aqueous electrolytic conduction on the sample surface. It is instead suggested that adsorbed water molecules alter the surface resistivity in a manner similar to that observed in semiconductors and insulators.

  7. Rock-brine chemical interactions. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1982-02-01

    The results of experimental interaction of powdered volcanic rock with aqueous solutions are presented at temperatures from 200 to 400/sup 0/C, 500 to 1000 bars fluid pressure, with reaction durations of approximately 30 days under controlled laboratory conditions. The aim of this research is to develop data on the kinetics and equilibria of rock solution interactions that will provide insight into the complex geochemical processes attending geothermal reservoir development, stimulation, and reinjection. The research was done in the Stanford Hydrothermal Lab using gold cell equipment of the Dickson design. This equipment inverts the solution rock mixture several times a minute to ensure thorough mixing. Solution samples were periodically withdrawn without interruption of the experimental conditions. The data from these experiments suggests a path dependent series of reactions by which geothermal fluids might evolve from meteoric or magmatic sources.

  8. A Global Protein Kinase and Phosphatase Interaction Network in Yeast

    Science.gov (United States)

    Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

    2011-01-01

    The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

  9. Airborne particulate matter in vitro exposure induces cytoskeleton remodeling through activation of the ROCK-MYPT1-MLC pathway in A549 epithelial lung cells.

    Science.gov (United States)

    Chirino, Yolanda I; García-Cuellar, Claudia María; García-García, Carlos; Soto-Reyes, Ernesto; Osornio-Vargas, Álvaro Román; Herrera, Luis A; López-Saavedra, Alejandro; Miranda, Javier; Quintana-Belmares, Raúl; Pérez, Irma Rosas; Sánchez-Pérez, Yesennia

    2017-04-15

    Airborne particulate matter with an aerodynamic diameter ≤10μm (PM 10 ) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM 10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM 10 exposure in A549 lung epithelial cells. Results showed that 10μg/cm 2 of PM 10 had no influence on cell viability but increased actin stress fibers, cytoplasmic ROCK expression, and phosphorylation of myosin phosphatase-targeting 1 (MYPT1) and myosin light chain (MLC) proteins, which are targeted by ROCK. The inhibition of ROCK prevented actin stress fiber formation and the phosphorylation of MYPT1 and MLC, suggesting that PM 10 activated the ROCK-MYPT1-MLC pathway in lung epithelial cells. The activation of ROCK1 has been involved in the acquisition of malignant phenotypes, and its induction by PM 10 exposure could contribute to the understanding of PM 10 as a risk factor for cancer development through the mechanisms associated with invasive phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Protein phosphatases active on acetyl-CoA carboxylase phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Witters, L.A.; Bacon, G.W.

    1985-01-01

    The protein phosphatases in rat liver cytosol, active on rat liver acetyl-CoA carboxylase (ACC) phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase, have been partially purified by anion-exchange and gel filtration chromatography. The major phosphatase activities against all three substrates copurify through fractionation and appear to be identical to protein phosphatases 2A1 and 2A2. No unique protein phosphatase active on 32 P-ACC phosphorylated by the casein kinases was identified

  11. Musical Structure as Narrative in Rock

    Directory of Open Access Journals (Sweden)

    John Fernando Encarnacao

    2011-09-01

    Full Text Available In an attempt to take a fresh look at the analysis of form in rock music, this paper uses Susan McClary’s (2000 idea of ‘quest narrative’ in Western art music as a starting point. While much pop and rock adheres to the basic structure of the establishment of a home territory, episodes or adventures away, and then a return, my study suggests three categories of rock music form that provide alternatives to common combinations of verses, choruses and bridges through which the quest narrative is delivered. Labyrinth forms present more than the usual number of sections to confound our sense of ‘home’, and consequently of ‘quest’. Single-cell forms use repetition to suggest either a kind of stasis or to disrupt our expectations of beginning, middle and end. Immersive forms blur sectional divisions and invite more sensual and participatory responses to the recorded text. With regard to all of these alternative approaches to structure, Judy Lochhead’s (1992 concept of ‘forming’ is called upon to underline rock music forms that unfold as process, rather than map received formal constructs. Central to the argument are a couple of crucial definitions. Following Theodore Gracyk (1996, it is not songs, as such, but particular recordings that constitute rock music texts. Additionally, narrative is understood not in (direct relation to the lyrics of a song, nor in terms of artists’ biographies or the trajectories of musical styles, but considered in terms of musical structure. It is hoped that this outline of non-narrative musical structures in rock may have applications not only to other types of music, but to other time-based art forms.

  12. Geomechanical rock properties of a basaltic volcano

    Directory of Open Access Journals (Sweden)

    Lauren N Schaefer

    2015-06-01

    Full Text Available In volcanic regions, reliable estimates of mechanical properties for specific volcanic events such as cyclic inflation-deflation cycles by magmatic intrusions, thermal stressing, and high temperatures are crucial for building accurate models of volcanic phenomena. This study focuses on the challenge of characterizing volcanic materials for the numerical analyses of such events. To do this, we evaluated the physical (porosity, permeability and mechanical (strength properties of basaltic rocks at Pacaya Volcano (Guatemala through a variety of laboratory experiments, including: room temperature, high temperature (935 °C, and cyclically-loaded uniaxial compressive strength tests on as-collected and thermally-treated rock samples. Knowledge of the material response to such varied stressing conditions is necessary to analyze potential hazards at Pacaya, whose persistent activity has led to 13 evacuations of towns near the volcano since 1987. The rocks show a non-linear relationship between permeability and porosity, which relates to the importance of the crack network connecting the vesicles in these rocks. Here we show that strength not only decreases with porosity and permeability, but also with prolonged stressing (i.e., at lower strain rates and upon cooling. Complimentary tests in which cyclic episodes of thermal or load stressing showed no systematic weakening of the material on the scale of our experiments. Most importantly, we show the extremely heterogeneous nature of volcanic edifices that arise from differences in porosity and permeability of the local lithologies, the limited lateral extent of lava flows, and the scars of previous collapse events. Input of these process-specific rock behaviors into slope stability and deformation models can change the resultant hazard analysis. We anticipate that an increased parameterization of rock properties will improve mitigation power.

  13. Ionization and Corona Discharges from Stressed Rocks

    Science.gov (United States)

    Winnick, M. J.; Kulahci, I.; Cyr, G.; Tregloan-Reed, J.; Freund, F. T.

    2008-12-01

    Pre-earthquake signals have long been observed and documented, though they have not been adequately explained scientifically. These signals include air ionization, occasional flashes of light from the ground, radio frequency emissions, and effects on the ionosphere that occur hours or even days before large earthquakes. The theory that rocks function as p-type semiconductors when deviatoric stresses are applied offers a mechanism for this group of earthquake precursors. When an igneous or high-grade metamorphic rock is subjected to deviatoric stresses, peroxy bonds that exist in the rock's minerals as point defects dissociate, releasing positive hole charge carriers. The positive holes travel by phonon-assisted electron hopping from the stressed into and through the unstressed rock volume and build up a positive surface charge. At sufficiently large electric fields, especially along edges and sharp points of the rock, air molecules become field-ionized, loosing an electron to the rock surface and turning into airborne positive ions. This in turn can lead to corona discharges, which manifest themselves by flashes of light and radio frequency emissions. We applied concentrated stresses to one end of a block of gabbro, 30 x 15 x 10 cm3, inside a shielded Faraday cage and observed positive ion currents through an air gap about 25 cm from the place where the stresses were applied, punctuated by short bursts, accompanied by flashes of light and radio frequency emissions characteristic of a corona discharge. These observations may serve to explain a range of pre-earthquake signals, in particular changes in air conductivity, luminous phenomena, radio frequency noise, and ionospheric perturbations.

  14. Anisotropy effect on strengths of metamorphic rocks

    Directory of Open Access Journals (Sweden)

    Ahmet Özbek

    2018-02-01

    Full Text Available This paper aims to study the effect of anisotropy on strengths of several metamorphic rocks of southern (Çine submassif of Menderes metamorphic massif in southwest Turkey. Four different metamorphic rocks including foliated phyllite, schist, gneiss and marble (calcschist were selected and examined. Discontinuity surveys were made along lines for each rock and evaluated with DIPS program. L-type Schmidt hammer was applied in the directions parallel and perpendicular to foliation during the field study. Several hand samples and rock blocks were collected during the field study for measurements of dry and saturated densities, dry and saturated unit weights and porosity, and for petrographic analysis and strength determination in laboratory. L- and N-type Schmidt hammers were applied in the directions perpendicular (anisotropy angle of 0° and parallel (anisotropy angle of 90° to the foliation on selected blocks of phyllite, schist, gneiss and marble (calcschist. The phyllite and schist have higher porosity and lower density values than the other rocks. However, coarse crystalline gneiss and marble (calcschist have higher rebound values and strengths, and they are classified as strong–very strong rocks. Generally, the rebound values in the direction perpendicular to the foliation are slightly higher than that in the direction parallel to foliation. Rebound values of N-type Schmidt hammer are higher than the L-type values except for phyllite. Sometimes, the rebound values of laboratory and field applications gave different results. This may result from variable local conditions such as minerals differentiation, discontinuities, water content, weathering degree and thickness of foliated structure.

  15. Src family kinases in chronic kidney disease.

    Science.gov (United States)

    Wang, Jun; Zhuang, Shougang

    2017-09-01

    Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved. Copyright © 2017 the American Physiological Society.

  16. Tyrosine kinase signalling in breast cancer

    International Nuclear Information System (INIS)

    Hynes, Nancy E

    2000-01-01

    Cells are continuously exposed to diverse stimuli ranging from soluble endocrine and paracrine factors to signalling molecules on neighbouring cells. Receptors of the tyrosine kinase family play an important role in the integration and interpretation of these external stimuli, allowing a cell to respond appropriately to its environment. The activation of receptor tyrosine kinases (RTKs) is tightly controlled, allowing a normal cell to correctly integrate its external environment with internal signal transduction pathways. In contrast, due to numerous molecular alterations arising during the course of malignancy, a tumour is characterized by an abnormal response to its environment, which allows cancer cells to evade the normal mechanisms controlling cellular proliferation. Alterations in the expression of various RTKs, in their activation, and in the signalling molecules lying downstream of the receptors play important roles in the development of cancer. This topic is the major focus of the thematic review section of this issue of Breast Cancer Research

  17. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    International Nuclear Information System (INIS)

    Boura, Evzen; Nencka, Radim

    2015-01-01

    The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine

  18. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Boura, Evzen, E-mail: boura@uochb.cas.cz; Nencka, Radim, E-mail: nencka@uochb.cas.cz

    2015-10-01

    The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine.

  19. Ror receptor tyrosine kinases: orphans no more.

    Science.gov (United States)

    Green, Jennifer L; Kuntz, Steven G; Sternberg, Paul W

    2008-11-01

    Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either activate or repress transcription of Wnt target genes and can modulate Wnt signaling by sequestering Wnt ligands. New evidence implicates Ror proteins in planar cell polarity, an alternative Wnt pathway. Here, we review the progress made in understanding these mysterious proteins and, in particular, we focus on their function as Wnt receptors.

  20. Aespoe Hard Rock Laboratory Annual Report 1999

    International Nuclear Information System (INIS)

    2000-08-01

    The Aespoe Hard Rock Laboratory has been constructed as part of the preparations for the deep geological repository for spent nuclear fuel in Sweden. The Tracer Retention Understanding Experiments are made to gain a better understanding of radionuclide retention in the rock and create confidence in the radionuclide transport models that are intended to be used in the licensing of a deep repository for spent fuel. The TRUE -1 experiment including tests with sorbing radioactive tracers in a single fracture over a distance of about 5 m has been completed. Diffusion and sorption in the rock matrix is the dominant retention mechanism over the time scales of the experiments. The main objective of the TRUE Block Scale Experiment is to increase understanding and our ability to predict tracer transport in a fracture network over spatial scales of 10 to 50 m. In total six boreholes have been drilled into the experimental volume located at the 450 m level. The Long-Term Diffusion Experiment is intended as a complement to the dynamic in-situ experiments and the laboratory experiments performed in the TRUE Programme. Diffusion from a fracture into the rock matrix will be studied in situ. The REX project focuses on the reduction of oxygen in a repository after closure due to reactions with rock minerals and microbial activity. Results show that oxygen is consumed within a few days both for the field and laboratory experiments. A new site for the CHEMLAB experiments was selected and prepared during 1999. All future experiment will be conducted in the J niche at 450 m depth. The Prototype Repository Test is focused on testing and demonstrating repository system function. A full-scale prototype including six deposition holes with canisters with electric heaters surrounded by highly compacted bentonite will be built and instrumented. Characterisation of the rock mass in the area of the Prototype repository is completed and the six deposition holes have been drilled. The Backfill and

  1. "All Yugoslavia Is Dancing Rock and Roll"

    DEFF Research Database (Denmark)

    Jovanovic, Zlatko

    with the arrival of New Wave into the country in the late 1970s. The study is carried through micro-historical analyses of the local rock scenes in the country’s four principal rock centres: Belgrade, Zagreb, Sarajevo and Ljubljana. The scenes are used as empirical platforms for discussing broader issues...... assumption of intertextuality, stressing that a text can only communicate its meaning when situated in relation to other texts, as the meaning always “arises” between texts. The thesis demonstrates that although Socialist Yugoslavia did not advocate creation of a supranational Yugoslav identity, but indeed...

  2. Energy Expenditure in Rock/Pop Drumming

    OpenAIRE

    De La Rue, S; Draper, Stephen B; Potter, Christopher R; Smith, M.

    2013-01-01

    Despite the vigorous nature of rock/pop drumming, there are no precise data on the energy expenditure of this activity. The aim of this study was to quantify the energy cost of rock/pop drumming. Fourteen male drummers (mean +/- SD; age 27 +/- 8 yrs.) completed an incremental drumming test to establish the relationship between energy expenditure and heart rate for this activity and a ramped cycle ergometer test to exhaustion as a criterion measure for peak values (oxygen uptake and heart rate...

  3. Migration of radionuclides in fissured rock

    International Nuclear Information System (INIS)

    Neretnieks, I.

    1982-01-01

    Some computed results of radionuclide migration in fissured rock are presented. The computations are based on a model which describes flow as occurring in a multitude of independent fissures (stratified flow). This gives rise to strong dispersion of channeling. The radionuclide migration in the individual fissures is modelled by the advection equation on a parallel walled channel with porous walls. The nuclides may diffuse into the pores and sorb reversibly on the pore surfaces. The effluent rates of 23 important nuclides are presented as functions of distance and time for various of important parameters such as rock permeability, diffusion coefficients, release rates, time of first release, fissure spacing and fissure width distribution. (Author)

  4. Aespoe Hard Rock Laboratory Annual Report 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-08-01

    The Aespoe Hard Rock Laboratory has been constructed as part of the preparations for the deep geological repository for spent nuclear fuel in Sweden. The Tracer Retention Understanding Experiments are made to gain a better understanding of radionuclide retention in the rock and create confidence in the radionuclide transport models that are intended to be used in the licensing of a deep repository for spent fuel. The TRUE -1 experiment including tests with sorbing radioactive tracers in a single fracture over a distance of about 5 m has been completed. Diffusion and sorption in the rock matrix is the dominant retention mechanism over the time scales of the experiments. The main objective of the TRUE Block Scale Experiment is to increase understanding and our ability to predict tracer transport in a fracture network over spatial scales of 10 to 50 m. In total six boreholes have been drilled into the experimental volume located at the 450 m level. The Long-Term Diffusion Experiment is intended as a complement to the dynamic in-situ experiments and the laboratory experiments performed in the TRUE Programme. Diffusion from a fracture into the rock matrix will be studied in situ. The REX project focuses on the reduction of oxygen in a repository after closure due to reactions with rock minerals and microbial activity. Results show that oxygen is consumed within a few days both for the field and laboratory experiments. A new site for the CHEMLAB experiments was selected and prepared during 1999. All future experiment will be conducted in the J niche at 450 m depth. The Prototype Repository Test is focused on testing and demonstrating repository system function. A full-scale prototype including six deposition holes with canisters with electric heaters surrounded by highly compacted bentonite will be built and instrumented. Characterisation of the rock mass in the area of the Prototype repository is completed and the six deposition holes have been drilled. The Backfill and

  5. Petrological studies of plutonic rocks of Ecuador

    International Nuclear Information System (INIS)

    Aly, S.

    1980-01-01

    The feldspars of many tonalitic plutonic rocks in the coastal regions and West Andean regions are zoned. This leads to the conclusion that they are relatively flat intrusions and to some extent transition rocks in the subvulcanite direction. This is in accordance with the genetic and chronological relationship between plutonites and the surrounding vulcanites of the Basic Igreous Complex (BIC). The composition of representative minerals, e.g. alkali feldspar, plagioclase feldspar, biotite, chlorite, and amphibole has been determined as well as the age of plutonite samples by the K/Ar dating method. (DG) [de

  6. Optically stimulated luminescence dating of rock surfaces

    DEFF Research Database (Denmark)

    Sohbati, Reza

    There are many examples of rock surfaces, rock art and stone structures whose ages are of great importance to the understanding of various phenomena in geology, climatology and archaeology. Optically stimulated luminescence (OSL) dating is a well-established chronological tool that has successfully...... to include the effects of the environmental dose rate. By fitting the model to the dose-depth variation from a single clast, four events (two light exposures of different durations each followed by a burial period) in the history of a single cobble are identified and quantified. However, the use of model...

  7. Rock support for nuclear waste repositories

    International Nuclear Information System (INIS)

    Abramson, L.W.; Schmidt, B.

    1984-01-01

    The design of rock support for underground nuclear waste repositories requires consideration of special construction and operation requirements, and of the adverse environmental conditions in which some of the support is placed. While repository layouts resemble mines, design, construction and operation are subject to quality assurance and public scrutiny similar to what is experienced for nuclear power plants. Exploration, design, construction and operation go through phases of review and licensing by government agencies as repositories evolve. This paper discusses (1) the various stages of repository development; (2) the environment that supports must be designed for; (3) the environmental effects on support materials; and (4) alternative types of repository rock support

  8. Aurora kinase inhibitors: Progress towards the clinic

    Czech Academy of Sciences Publication Activity Database

    Kollareddy, M.; Zheleva, D.; Dzubak, P.; Brahmkshatriya, Pathik; Lepšík, Martin; Hajduch, M.

    2012-01-01

    Roč. 30, č. 6 (2012), s. 2411-2432 ISSN 0167-6997 Grant - others:GA ČR(CZ) GA301/08/1649; GA ČR(CZ) GD303/09/H048 Program:GA; GD Institutional research plan: CEZ:AV0Z40550506 Keywords : Aurora kinases * cancer * inhibitors Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.498, year: 2012

  9. MAP kinases in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Olsen, Jørgen; Seidelin, Jakob Benedict

    2011-01-01

    The mammalian family of mitogen-activated protein kinases (MAPKs) is activated by diverse extracellular and intracellular stimuli, and thereby they play an essential role in connecting cell-surface receptors to changes in transcriptional programs. The MAPK signaling pathways regulate a wide range...... these signaling pathways have been exploited for the development of therapeutics and discuss the current knowledge of potential MAPK inhibitors and their anti-inflammatory effects in clinical trials related to IBD....

  10. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    Czech Academy of Sciences Publication Activity Database

    Bouřa, Evžen; Nencka, Radim

    2015-01-01

    Roč. 337, č. 2 (2015), s. 136-145 ISSN 0014-4827 R&D Projects: GA ČR GJ15-21030Y; GA MŠk LO1302; GA ČR GA15-09310S EU Projects: European Commission(XE) 333916 - STARPI4K Institutional support: RVO:61388963 Keywords : phosphatidylinositol 4-kinase * inhibitor * crystal structure * virus Subject RIV: CC - Organic Chemistry Impact factor: 3.378, year: 2015

  11. Molecular Imaging of the ATM Kinase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Terence M. [Department of Radiation Oncology, Ohio State University, Columbus, Ohio (United States); Nyati, Shyam [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Ross, Brian D. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Rehemtulla, Alnawaz, E-mail: alnawaz@umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2013-08-01

    Purpose: Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including from DNA double-strand breaks. ATM activation results in the initiation of a complex cascade of events including DNA damage repair, cell cycle checkpoint control, and survival. We sought to create a bioluminescent reporter that dynamically and noninvasively measures ATM kinase activity in living cells and subjects. Methods and Materials: Using the split luciferase technology, we constructed a hybrid cDNA, ATM-reporter (ATMR), coding for a protein that quantitatively reports on changes in ATM kinase activity through changes in bioluminescence. Results: Treatment of ATMR-expressing cells with ATM inhibitors resulted in a dose-dependent increase in bioluminescence activity. In contrast, induction of ATM kinase activity upon irradiation resulted in a decrease in reporter activity that correlated with ATM and Chk2 activation by immunoblotting in a time-dependent fashion. Nuclear targeting improved ATMR sensitivity to both ATM inhibitors and radiation, whereas a mutant ATMR (lacking the target phosphorylation site) displayed a muted response. Treatment with ATM inhibitors and small interfering (si)RNA-targeted knockdown of ATM confirm the specificity of the reporter. Using reporter expressing xenografted tumors demonstrated the ability of ATMR to report in ATM activity in mouse models that correlated in a time-dependent fashion with changes in Chk2 activity. Conclusions: We describe the development and validation of a novel, specific, noninvasive bioluminescent reporter that enables monitoring of ATM activity in real time, in vitro and in vivo. Potential applications of this reporter include the identification and development of novel ATM inhibitors or ATM-interacting partners through high-throughput screens and in vivo pharmacokinetic/pharmacodynamic studies of ATM inhibitors in preclinical models.

  12. Integration of rock typing methods for carbonate reservoir characterization

    International Nuclear Information System (INIS)

    Aliakbardoust, E; Rahimpour-Bonab, H

    2013-01-01

    Reservoir rock typing is the most important part of all reservoir modelling. For integrated reservoir rock typing, static and dynamic properties need to be combined, but sometimes these two are incompatible. The failure is due to the misunderstanding of the crucial parameters that control the dynamic behaviour of the reservoir rock and thus selecting inappropriate methods for defining static rock types. In this study, rock types were defined by combining the SCAL data with the rock properties, particularly rock fabric and pore types. First, air-displacing-water capillary pressure curues were classified because they are representative of fluid saturation and behaviour under capillary forces. Next the most important rock properties which control the fluid flow and saturation behaviour (rock fabric and pore types) were combined with defined classes. Corresponding petrophysical properties were also attributed to reservoir rock types and eventually, defined rock types were compared with relative permeability curves. This study focused on representing the importance of the pore system, specifically pore types in fluid saturation and entrapment in the reservoir rock. The most common tests in static rock typing, such as electrofacies analysis and porosity–permeability correlation, were carried out and the results indicate that these are not appropriate approaches for reservoir rock typing in carbonate reservoirs with a complicated pore system. (paper)

  13. Abnormal Activation of RhoA/ROCK-I Signaling in Junctional Zone Smooth Muscle Cells of Patients With Adenomyosis.

    Science.gov (United States)

    Wang, S; Duan, H; Zhang, Y; Sun, F Q

    2016-03-01

    Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. The RhoA/Rho-kinase (ROCK) signaling pathway is involved in various cellular functions, including migration, proliferation, and smooth muscle contraction. Here we examined the potential role of this pathway in junctional zone (JZ) contraction in women with and without ADS. We demonstrated that in the normal JZ, RhoA and ROCK-I messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. Expression of RhoA and ROCK-I in the JZ from women with ADS was significantly higher than in the control women and showed no significant differences across the menstrual cycle. Treatment of JZ smooth muscle cells (JZSMCs) with estrogen at 0, 1, 10, or 100 nmol/L for 24 hours resulted in increased expression of RhoA, ROCK-I, and myosin light-chain (MLC) phosphorylation (p-MLC) in a dose-dependent manner. In parallel to its effects on p-MLC, estrogen-mediated, dose-dependent contraction responses in JZSMCs. Estrogen-mediated contraction in the ADS group was significantly higher than in the controls and also showed no significant differences across the menstrual cycle. These effects were suppressed in the presence of ICI 182780 or Y27632, supporting an estrogen receptor-dependent and RhoA activation-dependent mechanism. Our results indicate that the level of RhoA and ROCK-I increases in patients with ADS and the cyclic change is lost. Estrogen may affect uterine JZ contraction of ADS by enhancing RhoA/ ROCK-I signaling. © The Author(s) 2015.

  14. Water-rock interaction in a high-FeO olivine rock in nature

    International Nuclear Information System (INIS)

    Hellmuth, K.H.; Lindberg, A.; Tullborg, E.L.

    1992-12-01

    The long-term behaviour in nature of high-FeO olivine rock in contact with surface water has been studied at the Lovasjaervi instrusion, SE-Finland. The rock has been proposed as a high-capasity, higly reactive redox-buffer backfill in a repository for spent fuel. Favourable groundwater chemistry is a major parameter relevant to safety of such a repository. Reducing conditions favour the retardation of long-lived, redox-sensitive radionuclides. Weathering influences have been studied at the natural outcrop of the rock mass. The interaction of oxidizing surface waters with rock at greater depths has been studied by using fissure filling minerals. Investigation of weathered rock from the outcrop indicates that the olivine rock is highly reactive on a geological time scale and its redox capasity is available although the instrusion as a whole is surprisingly well preserved. The fissure fillings studied allow the conclusion that oxygen seems to be efficiently removed from intruding surface water. Oxidation seem to have caused visible effects only along very conducting fractures and near the contact zones of the surrounding granitic rock. Stable isotope data of fissure filling calcites indicate that the influence of surface waters can be traced clearly down to a depth of about 50 m, but also at greater depths re-equilibration has occurred. Groundwater data from the site were not available. (orig.)

  15. Interim rock mass properties and conditions for analyses of a repository in crystalline rock

    International Nuclear Information System (INIS)

    Tammemagi, H.Y.; Chieslar, J.D.

    1985-03-01

    A summary of rock properties for generic crystalline rock is compiled from literature sources to provide the input data for analyses of a conceptual repository in crystalline rock. Frequency histograms, mean values and ranges of physical, mechanical, thermal, and thermomechanical properties, and the dependence of these properties on temperature are described. A description of the hydrogeologic properties of a crystalline rock mass and their dependence on depth is provided. In addition, the temperature gradients, mean annual surface temperature, and in situ stress conditions are summarized for the three regions of the United States currently under consideration to host a crystalline repository; i.e., the North Central, Northeastern, and Southeastern. Brief descriptions of the regional geology are also presented. Large-scale underground experiments in crystalline rock at Stripa, Sweden, and in Climax Stock in Nevada, are reviewed to assess whether the rock properties presented in this report are representative of in situ conditions. The suitability of each rock property and the sufficiency of its data base are described. 110 refs., 27 figs., 4 tabs

  16. Bioremediation in Fractured Rock: 2. Mobilization of Chloroethene Compounds from the Rock Matrix.

    Science.gov (United States)

    Shapiro, Allen M; Tiedeman, Claire R; Imbrigiotta, Thomas E; Goode, Daniel J; Hsieh, Paul A; Lacombe, Pierre J; DeFlaun, Mary F; Drew, Scott R; Curtis, Gary P

    2018-03-01

    A mass balance is formulated to evaluate the mobilization of chlorinated ethene compounds (CE) from the rock matrix of a fractured mudstone aquifer under pre- and postbioremediation conditions. The analysis relies on a sparse number of monitoring locations and is constrained by a detailed description of the groundwater flow regime. Groundwater flow modeling developed under the site characterization identified groundwater fluxes to formulate the CE mass balance in the rock volume exposed to the injected remediation amendments. Differences in the CE fluxes into and out of the rock volume identify the total CE mobilized from diffusion, desorption, and nonaqueous phase liquid dissolution under pre- and postinjection conditions. The initial CE mass in the rock matrix prior to remediation is estimated using analyses of CE in rock core. The CE mass mobilized per year under preinjection conditions is small relative to the total CE mass in the rock, indicating that current pump-and-treat and natural attenuation conditions are likely to require hundreds of years to achieve groundwater concentrations that meet regulatory guidelines. The postinjection CE mobilization rate increased by approximately an order of magnitude over the 5 years of monitoring after the amendment injection. This rate is likely to decrease and additional remediation applications over several decades would still be needed to reduce CE mass in the rock matrix to levels where groundwater concentrations in fractures achieve regulatory standards. © 2017, National Ground Water Association.

  17. Bioremediation in fractured rock: 2. Mobilization of chloroethene compounds from the rock matrix

    Science.gov (United States)

    Shapiro, Allen M.; Tiedeman, Claire; Imbrigiotta, Thomas; Goode, Daniel J.; Hsieh, Paul A.; Lacombe, Pierre; DeFlaun, Mary F.; Drew, Scott R.; Curtis, Gary P.

    2018-01-01

    A mass balance is formulated to evaluate the mobilization of chlorinated ethene compounds (CE) from the rock matrix of a fractured mudstone aquifer under pre- and postbioremediation conditions. The analysis relies on a sparse number of monitoring locations and is constrained by a detailed description of the groundwater flow regime. Groundwater flow modeling developed under the site characterization identified groundwater fluxes to formulate the CE mass balance in the rock volume exposed to the injected remediation amendments. Differences in the CE fluxes into and out of the rock volume identify the total CE mobilized from diffusion, desorption, and nonaqueous phase liquid dissolution under pre- and postinjection conditions. The initial CE mass in the rock matrix prior to remediation is estimated using analyses of CE in rock core. The CE mass mobilized per year under preinjection conditions is small relative to the total CE mass in the rock, indicating that current pump-and-treat and natural attenuation conditions are likely to require hundreds of years to achieve groundwater concentrations that meet regulatory guidelines. The postinjection CE mobilization rate increased by approximately an order of magnitude over the 5 years of monitoring after the amendment injection. This rate is likely to decrease and additional remediation applications over several decades would still be needed to reduce CE mass in the rock matrix to levels where groundwater concentrations in fractures achieve regulatory standards.

  18. Pea DNA topoisomerase I is phosphorylated and stimulated by casein kinase 2 and protein kinase C.

    Science.gov (United States)

    Tuteja, Narendra; Reddy, Malireddy Kodandarami; Mudgil, Yashwanti; Yadav, Badam Singh; Chandok, Meena Rani; Sopory, Sudhir Kumar

    2003-08-01

    DNA topoisomerase I catalyzes the relaxation of superhelical DNA tension and is vital for DNA metabolism; therefore, it is essential for growth and development of plants. Here, we have studied the phosphorylation-dependent regulation of topoisomerase I from pea (Pisum sativum). The purified enzyme did not show autophosphorylation but was phosphorylated in an Mg(2+)-dependent manner by endogenous protein kinases present in pea nuclear extracts. This phosphorylation was abolished with calf intestinal alkaline phosphatase and lambda phosphatase. It was also phosphorylated by exogenous casein kinase 2 (CK2), protein kinase C (PKC; from animal sources), and an endogenous pea protein, which was purified using a novel phorbol myristate acetate affinity chromatography method. All of these phosphorylations were inhibited by heparin (inhibitor of CK2) and calphostin (inhibitor of PKC), suggesting that pea topoisomerase I is a bona fide substrate for these kinases. Spermine and spermidine had no effect on the CK2-mediated phosphorylation, suggesting that it is polyamine independent. Phospho-amino acid analysis showed that only serine residues were phosphorylated, which was further confirmed using antiphosphoserine antibody. The topoisomerase I activity increased after phosphorylation with exogenous CK2 and PKC. This study shows that these kinases may contribute to the physiological regulation of DNA topoisomerase I activity and overall DNA metabolism in plants.

  19. CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.

    Science.gov (United States)

    Leonardi, A; Chariot, A; Claudio, E; Cunningham, K; Siebenlist, U

    2000-09-12

    Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKgamma in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.

  20. CIKS, a connection to IκB kinase and stress-activated protein kinase

    Science.gov (United States)

    Leonardi, Antonio; Chariot, Alain; Claudio, Estefania; Cunningham, Kirk; Siebenlist, Ulrich

    2000-01-01

    Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-κB and AP-1/ATF families. Activation of NF-κB factors is thought to be mediated primarily via IκB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKα and IKKβ are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-κB essential modulator)/IKKγ. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKγ in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-κB-dependent reporter. Activation of NF-κB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins. PMID:10962033