Cyclic Stretch Alters Vascular Reactivity of Mouse Aortic Segments

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Arthur Leloup

2017-10-01

Full Text Available Large, elastic arteries buffer the pressure wave originating in the left ventricle and are constantly exposed to higher amplitudes of cyclic stretch (10% than muscular arteries (2%. As a crucial factor for endothelial and smooth muscle cell function, cyclic stretch has, however, never been studied in ex vivo aortic segments of mice. To investigate the effects of cyclic stretch on vaso-reactivity of mouse aortic segments, we used the Rodent Oscillatory Tension Set-up to study Arterial Compliance (ROTSAC. The aortic segments were clamped at frequencies of 6–600 bpm between two variable preloads, thereby mimicking dilation as upon left ventricular systole and recoiling as during diastole. The preloads corresponding to different transmural pressures were chosen to correspond to a low, normal or high amplitude of cyclic stretch. At different time intervals, cyclic stretch was interrupted, the segments were afterloaded and isometric contractions by α1-adrenergic stimulation with 2 μM phenylephrine in the absence and presence of 300 μM L-NAME (eNOS inhibitor and/or 35 μM diltiazem (blocker of voltage-gated Ca2+ channels were measured. As compared with static or cyclic stretch at low amplitude (<10 mN or low frequency (0.1 Hz, cyclic stretch at physiological amplitude (>10 mN and frequency (1–10 Hz caused better ex vivo conservation of basal NO release with time after mounting. The relaxation of PE-precontracted segments by addition of ACh to stimulate NO release was unaffected by cyclic stretch. In the absence of basal NO release (hence, presence of L-NAME, physiological in comparison with aberrant cyclic stretch decreased the baseline tension, attenuated the phasic contraction by phenylephrine in the absence of extracellular Ca2+ and shifted the smaller tonic contraction more from a voltage-gated Ca2+ channel-mediated to a non-selective cation channel-mediated. Data highlight the need of sufficient mechanical activation of endothelial and

Cyclic AMP in rat pancreatic islets

International Nuclear Information System (INIS)

Grill, V.; Borglund, E.; Cerasi, E.; Uppsala Univ.

1977-01-01

The incorporation of [ 3 H]adenine into cyclic AMP was studied in rat pancreatic islets under varying conditions of labeling. Prolonging the exposure to [ 3 H]adenine progressively augmented the islet cyclic [ 3 H]AMP level. Islets labeled for different periods of time and subsequently incubated (without adenine) in the presence of D-glucose or cholera toxin showed stimulations of intra-islet cyclic [ 3 H]AMP that were proportionate to the levels of radioactive nucleotide present under non-stimulatory conditions. Labeling the islets in a high glucose concentration (27.7 mM) did not modify the nucleotide responses to glucose or cholera toxin. The specific activity of cyclic [ 3 H]AMP, determined by simultaneous assay of cyclic [ 3 H]AMP and total cyclic AMP, was not influenced by glucose or cholera toxin. Glucose had no effect on the specific activity of labeled ATP

Enhancing heavy oil recovery using foam injection in applications to cyclic steam stimulation

Energy Technology Data Exchange (ETDEWEB)

Isaacs, E. [Alberta Energy Research Inst., Edmonton, AB (Canada); Yuan, J.Y. [Canadian Natural Resources Ltd., Calgary, AB (Canada)

2008-07-01

Cyclic steam stimulation (CSS) is a widely used heavy oil production technology. However, steam-based processes that are not stabilized can develop conformance as the steam can over-ride and channel past oil-bearing zones. This presentation discussed a refined CSS steam foaming process designed to improve recovery in marginal cycles. Laboratory studies were initially conducted to examine surfactant properties and flow behaviour in porous media. The results of numerical simulations were then applied to the steam-foaming portion of the CSS process. Results of the study showed that during the foam co-injection with steam stage, the steam injection rate did not alter. Improvement to the CSS process varied, indicating that earlier foam forming surfactant co-injection was preferable when steam-foam performance was constant in all cycles. It was concluded that the steam foaming process may improve bitumen production without requiring additional steam. 13 refs., 5 figs.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

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Ivana Škrnjug

Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

Science.gov (United States)

Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

2014-01-01

The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

The influence of cyclic loading on gentamicin release from acrylic bone cements

NARCIS (Netherlands)

Hendriks, JGE; Neut, D; Hazenberg, JG; Verkerke, GJ; van Horn, [No Value; van der Mei, HC; Busscher, HJ

Antibiotic-loaded acrylic bone cement is widely used in total joint replacement to reduce infections. Walking results in cyclic loading, which has been suggested to stimulate antibiotic release. The goal of this study is to compare antibiotic release from cyclically loaded bone cement with the

Insulin: its binding to specific receptors and its stimulation of DNA synthesis and 2',3'-cyclic nucleotide phosphohydrolase in embryonic mouse brain cell cultures

International Nuclear Information System (INIS)

Shanker, G.; Pieringer, R.A.

1986-01-01

Previously, the authors demonstrated that ornithine decarboxylase was stimulated by insulin in cultures of embryonic mouse brain cells. In the present work, they have investigated the presence and specificity of insulin receptors in these cultures. A time study showed that maximum binding of 125 [I] labelled insulin was around 75 min. Other studies measured the influence of concentration and age on insulin binding. A displacement study using increasing concentrations of cold insulin, glucagon or growth hormone demonstrated that the specificity of the receptors for insulin was rather high. It was also found that insulin displayed a clear dose-dependent stimulation of thymidine incorporation into the brain cells. Insulin also stimulated the glial enzyme 2':3'-cyclic nucleotide phosphohydrolase (CNP-ase). The results suggest a dual role for insulin; it regulates both cell proliferation as well as differentiation

Cyclic AMP-dependent protein kinase interferes with GTP γS stimulated IP3 formation in differentiated HL-60 cell membranes

International Nuclear Information System (INIS)

Misaki, Naoyuki; Imaizumi, Taro; Watanabe, Yashuiro

1989-01-01

The effects of addition of activated cyclic AMP-dependent protein kinase (PKA) on the function of islet-activating protein (IAP)-sensitive GTP-binding (G) protein were studied in the plasma membranes of 3 H-inositol-labeled differentiated human leukemic (HL-60) cells. Pretreatment of the membranes with activated PKA in the presence of MgATP for 15 min. at 37 degree C decreased GTP γS-stimulated inositol trisphosphate (IP 3 ) formation by about 30%, but had no influence on Ca 2+ -stimulated IP 3 formation. And autoradiography in the phosphorylation experiments of solubilized HL-60 cell membranes by PKA showed some 32 P incorporated bands, and among them one of the major bands showed the migration at 40 kDa supporting that the G protein coupling with PI response was phosphorylated by PKA. These results showed that pretreatment with activated PKA inhibited the mediating function of the G protein between the fMLP receptor and phospholipase C by its phosphorylation

Synthesis of interleukin 6 (interferon-β2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

International Nuclear Information System (INIS)

Zhange, Y.; Lin, J.X.; Vilcek, J.

1988-01-01

Interleukin 6 (IL-6; also referred to as interferon-β 2 , 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1

Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: functional and biochemical study.

Science.gov (United States)

Cortijo, J; Naline, E; Ortiz, J L; Berto, L; Girard, V; Malbezin, M; Advenier, C; Morcillo, E J

1998-01-02

We have investigated the role of human bronchial cyclic nucleotide phosphodiesterases in the effects of fenspiride, a drug endowed with bronchodilator and anti-inflammatory properties. Functional studies on human isolated bronchi showed that fenspiride (10(-6)-3 x 10(-3) M, 30 min) induced a shift to the left of the concentration-response curves for isoprenaline and sodium nitroprusside with -logEC50 values of 4.1+/-0.1 (n = 7) and 3.5+/-0.2 (n = 8), respectively. Biochemical studies were carried out on three human bronchi in which separation of cyclic nucleotide phosphodiesterase isoenzymes was performed by ion exchange chromatography followed by determination of phosphodiesterase activity with a radioisotopic method. Phosphodiesterase 4 (cyclic AMP-specific) and phosphodiesterase 5 (cyclic GMP-specific) were the major phosphodiesterase isoforms present in the human bronchial tissue. The presence of phosphodiesterase 1 (Ca2+/calmodulin-stimulated), phosphodiesterase 2 (cyclic GMP-stimulated) and, in two cases, phosphodiesterase 3 (cyclic GMP-inhibited) was also identified. Fenspiride inhibited phosphodiesterase 4 and phosphodiesterase 3 activities with -logIC50 values of 4.16+/-0.09 and 3.44+/-0.12, respectively. Phosphodiesterase 5 activity was also inhibited with a -logIC50 value of approximately 3.8. Fenspiride (fenspiride is an effective inhibitor of both cyclic AMP and cyclic GMP hydrolytic activity in human bronchial tissues and this action may contribute to its airway effects.

Regulation of Maltodextrin Phosphorylase Synthesis in Escherichia coli by Cyclic Adenosine 3′, 5′-Monophosphate and Glucose1

Science.gov (United States)

Chao, Julie; Weathersbee, Carolyn J.

1974-01-01

Cyclic adenosine 3′, 5′-monophosphate (AMP) stimulates maltodextrin phosphorylase synthesis in Escherichia coli cells induced with maltose. A maximal effect occurs at 2 to 3 mM cyclic AMP. The action of cyclic AMP is specific, inasmuch as adenosine triphosphate, 3′-AMP, 5′-AMP, adenosine, and dibutyryl cyclic AMP are inactive. Glucose, α-methyl glucoside, 2-deoxyglucose, and pyridoxal 5′-phosphate repress maltodextrin phosphorylase synthesis. This repression is reversed by cyclic AMP. The action of cyclic AMP appears to be at the transcriptional level, since cyclic AMP fails to stimulate phosphorylase production in induced cells in which messenger ribonucleic acid synthesis has been arrested by rifampin or by inducer removal. The two other enzymes involved in the metabolism of maltose, amylomaltase and maltose permease, are also induced in this strain of E. coli and affected by glucose and cyclic AMP in a manner similar to phosphorylase. PMID:4358043

Effect of cyclic electron irradiation on mechanical properties of austenite steel

International Nuclear Information System (INIS)

Tsepelev, A.B.; Sadykhov, S.I.O.; Chernov, A.I.; Sevost'yanov, M.A.

2006-01-01

To check the supposition on the possibility of radiation-stimulated process enhancement under cyclic irradiation conditions an experimental investigation is carried out to elucidate the effect of the mode of irradiation (continuous or cyclic) on mechanical properties of chromium-manganese austenitic stainless steel type 10Kh12G20V. The effect of some radiation hardening is observed under cyclic irradiation, however, the data obtained cannot be considered as good evidence for the validity of proposed model of dynamic preference if the scatter in experimental data is taken into account [ru

Cyclic GMP-AMP Displays Mucosal Adjuvant Activity in Mice

OpenAIRE

Škrnjug, Ivana; Guzmán, Carlos Alberto; Ruecker, Christine

2014-01-01

The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice....

Cyclic AMP system in muscle tissue during prolonged hypokinesia

Science.gov (United States)

Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

1980-01-01

Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

Candida albicans ethanol stimulates Pseudomonas aeruginosa WspR-controlled biofilm formation as part of a cyclic relationship involving phenazines.

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Annie I Chen

2014-10-01

Full Text Available In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic-di-GMP (c-di-GMP, and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol stimulation of c-di-GMP. Multiple lines of evidence indicate that ethanol stimulates WspR signaling through its cognate sensor WspA, and promotes WspR-dependent activation of Pel exopolysaccharide production, which contributes to biofilm maturation. We also found that ethanol stimulation of WspR promoted P. aeruginosa colonization of CF airway epithelial cells. P. aeruginosa production of phenazines occurs both in the CF lung and in culture, and phenazines enhance ethanol production by C. albicans. Using a C. albicans adh1/adh1 mutant with decreased ethanol production, we found that fungal ethanol strongly altered the spectrum of P. aeruginosa phenazines in favor of those that are most effective against fungi. Thus, a feedback cycle comprised of ethanol and phenazines drives this polymicrobial interaction, and these relationships may provide insight into why co-infection with both P. aeruginosa and C. albicans has been associated with worse outcomes in cystic fibrosis.

Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data

Science.gov (United States)

2016-01-01

The neurotransmitter dopamine is heavily implicated in intracranial self-stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS. PMID:27548680

Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

Science.gov (United States)

Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

2018-02-21

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

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.

Proliferation-stimulating effect of colony stimulating factor 2 on porcine trophectoderm cells is mediated by activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase.

Directory of Open Access Journals (Sweden)

Wooyoung Jeong

Full Text Available Colony-stimulating factor 2 (CSF2, also known as granulocyte macrophage colony-stimulating factor, facilitates mammalian embryonic development and implantation. However, biological functions and regulatory mechanisms of action of porcine endometrial CSF2 in peri-implantation events have not been elucidated. The aim of present study was to determine changes in cellular activities induced by CSFs and to access CSF2-induced intracellular signaling in porcine primary trophectoderm (pTr cells. Differences in expression of CSF2 mRNA in endometrium from cyclic and pregnant gilts were evaluated. Endometrial CSF2 mRNA expression increases during the peri-implantation period, Days 10 to 14 of pregnancy, as compared to the estrous cycle. pTr cells obtained in Day 12 of pregnancy were cultured in the presence or absence of CSF2 (20 ng/ml and LY294002 (20 µM, U0126 (20 µM, rapamycin (20 nM, and SB203580 (20 µM. CSF2 in pTr cell culture medium at 20 ng/ml significantly induced phosphorylation of AKT1, ERK1/2, MTOR, p70RSK and RPS6 protein, but not STAT3 protein. Also, the PI3K specific inhibitor (LY294002 abolished CSF2-induced increases in p-ERK1/2 and p-MTOR proteins, as well as CSF2-induced phosphorylation of AKT1. Changes in proliferation and migration of pTr cells in response to CSF2 were examined in dose- and time-response experiments. CSF2 significantly stimulated pTr cell proliferation and, U0126, rapamycin and LY294002 blocked this CSF2-induced proliferation of pTr cells. Collectively, during the peri-implantation phase of pregnancy in pigs, endometrial CSF2 stimulates proliferation of trophectoderm cells by activation of the PI3K-and ERK1/2 MAPK-dependent MTOR signal transduction cascades.

The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia

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Mousumi Ghosh

2015-01-01

Full Text Available Cyclic AMP is an important intracellular regulator of microglial cell homeostasis and its negative perturbation through proinflammatory signaling results in microglial cell activation. Though cytokines, TNF-α and IL-1β, decrease intracellular cyclic AMP, the mechanism by which this occurs is poorly understood. The current study examined which signaling pathways are responsible for decreasing cyclic AMP in microglia following TNF-α stimulation and sought to identify the role cyclic AMP plays in regulating these pathways. In EOC2 microglia, TNF-α produced a dramatic reduction in cyclic AMP and increased cyclic AMP-dependent PDE activity that could be antagonized by Rolipram, myristoylated-PKI, PD98059, or JSH-23, implicating a role for PDE4, PKA, MEK, and NF-κB in this regulation. Following TNF-α there were significant increases in iNOS and COX-2 immunoreactivity, phosphorylated ERK1/2 and NF-κB-p65, IκB degradation, and NF-κB p65 nuclear translocation, which were reduced in the presence of high levels of cyclic AMP, indicating that reductions in cyclic AMP during cytokine stimulation are important for removing its inhibitory action on NF-κB activation and subsequent proinflammatory gene expression. Further elucidation of the signaling crosstalk involved in decreasing cyclic AMP in response to inflammatory signals may provide novel therapeutic targets for modulating microglial cell activation during neurological injury and disease.

Integrated wireless fast-scan cyclic voltammetry recording and electrical stimulation for reward-predictive learning in awake, freely moving rats

Science.gov (United States)

Li, Yu-Ting; Wickens, Jeffery R.; Huang, Yi-Ling; Pan, Wynn H. T.; Chen, Fu-Yu Beverly; Chen, Jia-Jin Jason

2013-08-01

Objective. Fast-scan cyclic voltammetry (FSCV) is commonly used to monitor phasic dopamine release, which is usually performed using tethered recording and for limited types of animal behavior. It is necessary to design a wireless dopamine sensing system for animal behavior experiments. Approach. This study integrates a wireless FSCV system for monitoring the dopamine signal in the ventral striatum with an electrical stimulator that induces biphasic current to excite dopaminergic neurons in awake freely moving rats. The measured dopamine signals are unidirectionally transmitted from the wireless FSCV module to the host unit. To reduce electrical artifacts, an optocoupler and a separate power are applied to isolate the FSCV system and electrical stimulator, which can be activated by an infrared controller. Main results. In the validation test, the wireless backpack system has similar performance in comparison with a conventional wired system and it does not significantly affect the locomotor activity of the rat. In the cocaine administration test, the maximum electrically elicited dopamine signals increased to around 230% of the initial value 20 min after the injection of 10 mg kg-1 cocaine. In a classical conditioning test, the dopamine signal in response to a cue increased to around 60 nM over 50 successive trials while the electrically evoked dopamine concentration decreased from about 90 to 50 nM in the maintenance phase. In contrast, the cue-evoked dopamine concentration progressively decreased and the electrically evoked dopamine was eliminated during the extinction phase. In the histological evaluation, there was little damage to brain tissue after five months chronic implantation of the stimulating electrode. Significance. We have developed an integrated wireless voltammetry system for measuring dopamine concentration and providing electrical stimulation. The developed wireless FSCV system is proven to be a useful experimental tool for the continuous

Differential regulation of human 3β-hydroxysteroid dehydrogenase type 2 for steroid hormone biosynthesis by starvation and cyclic AMP stimulation: studies in the human adrenal NCI-H295R cell model.

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Sameer Udhane

Full Text Available Human steroid biosynthesis depends on a specifically regulated cascade of enzymes including 3β-hydroxysteroid dehydrogenases (HSD3Bs. Type 2 HSD3B catalyzes the conversion of pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone to progesterone, 17α-hydroxyprogesterone and androstenedione in the human adrenal cortex and the gonads but the exact regulation of this enzyme is unknown. Therefore, specific downregulation of HSD3B2 at adrenarche around age 6-8 years and characteristic upregulation of HSD3B2 in the ovaries of women suffering from the polycystic ovary syndrome remain unexplained prompting us to study the regulation of HSD3B2 in adrenal NCI-H295R cells. Our studies confirm that the HSD3B2 promoter is regulated by transcription factors GATA, Nur77 and SF1/LRH1 in concert and that the NBRE/Nur77 site is crucial for hormonal stimulation with cAMP. In fact, these three transcription factors together were able to transactivate the HSD3B2 promoter in placental JEG3 cells which normally do not express HSD3B2. By contrast, epigenetic mechanisms such as methylation and acetylation seem not involved in controlling HSD3B2 expression. Cyclic AMP was found to exert differential effects on HSD3B2 when comparing short (acute versus long-term (chronic stimulation. Short cAMP stimulation inhibited HSD3B2 activity directly possibly due to regulation at co-factor or substrate level or posttranslational modification of the protein. Long cAMP stimulation attenuated HSD3B2 inhibition and increased HSD3B2 expression through transcriptional regulation. Although PKA and MAPK pathways are obvious candidates for possibly transmitting the cAMP signal to HSD3B2, our studies using PKA and MEK1/2 inhibitors revealed no such downstream signaling of cAMP. However, both signaling pathways were clearly regulating HSD3B2 expression.

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.

Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.

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Alicia Jiménez-Fernández

Full Text Available Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels.

Viral evasion of DNA-stimulated innate immune responses.

Science.gov (United States)

Christensen, Maria H; Paludan, Søren R

2017-01-01

Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.

Colony-stimulating factor (CSF) radioimmunoassay: detection of a CSF subclass stimulating macrophage production

International Nuclear Information System (INIS)

Stanley, E.R.

1979-01-01

Colony-stimulating factors (CSFs) stimulate the differentiation of immature precursor cells to mature granulocytes and macrophages. Purified 125 I-labeled murine L cell CSF has been used to develop a radioimmunoassay (RIA) that detects a subclass of CSFs that stimulates macrophage production. Murine CSF preparations that contain this subclass of CSF compete for all of the CSF binding sites on anti-L cell CSF antibody. With the exception of mouse serum, which can contain inhibitors of the bioassay, there is complete correspondence between activities determined by RIA and those determined by bioassay. The RIA is slightly more sensitive than the bioassay, detecting approximately 0.3 fmol of purified L cell CSF. It can also detect this subclass of CSF in chickens, rats, and humans. In the mouse, the subclass is distinguished from other CSFs by a murine cell bioassay dose-response curve in which 90% of the response occurs over a 10-fold (rather than a 100-fold) increase in concentration, by stimulating the formations of colonies contaning a high proportion of mononuclear (rather than granulocytic) cells, and by certain physical characteristics

Kinetics of activation of the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein.

Science.gov (United States)

Hoggett, J G; Brierley, I

1992-11-01

The activation of transcription initiation from the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein (CRP) has been investigated using a fluorescence abortive initiation assay. The effect of the cyclic-AMP/CRP complex on the linear P4 promoter was to increase the initial binding (KB) of RNA polymerase to the promoter by about a factor of 10, but the rate of isomerization of closed to open complex (kf) was unaffected. One molecule of CRP per promoter was required for activation, and the concentration of cyclic AMP producing half-maximal stimulation was about 7-8 microM. Supercoiling caused a 2-3-fold increase in the rate of isomerization of the CRP-activated promoter, but weakened the initial binding of polymerase by about one order of magnitude. The unactivated supercoiled promoter was too weak to allow reliable assessment of kinetic parameters against the high background rate originating from the rest of the plasmid.

Activation of the adenylyl cyclase/cyclic AMP/protein kinase A pathway in endothelial cells exposed to cyclic strain

Science.gov (United States)

Cohen, C. R.; Mills, I.; Du, W.; Kamal, K.; Sumpio, B. E.

1997-01-01

The aim of this study was to assess the involvement of the adenylyl cyclase/cyclic AMP/protein kinase A pathway (AC) in endothelial cells (EC) exposed to different levels of mechanical strain. Bovine aortic EC were seeded to confluence on flexible membrane-bottom wells. The membranes were deformed with either 150 mm Hg (average 10% strain) or 37.5 mm Hg (average 6% strain) vacuum at 60 cycles per minute (0.5 s strain; 0.5 s relaxation) for 0-60 min. The results demonstrate that at 10% average strain (but not 6% average strain) there was a 1.5- to 2.2-fold increase in AC, cAMP, and PKA activity by 15 min when compared to unstretched controls. Further studies revealed an increase in cAMP response element binding protein in EC subjected to the 10% average strain (but not 6% average strain). These data support the hypothesis that cyclic strain activates the AC/cAMP/PKA signal transduction pathway in EC which may occur by exceeding a strain threshold and suggest that cyclic strain may stimulate the expression of genes containing cAMP-responsive promoter elements.

Effects of oxytocin and methacholine on cyclic nucleotide levels of rabbit myometrium.

Science.gov (United States)

Schlageter, N; Janis, R A; Gualtieri, R T; Hechter, O

1980-03-01

The effects of oxytocin and methacholine on cyclic nucleotide levels in estrogen-primed rabbit myometrium were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor. In the absence of MIX, methacholine increased guanosine 3',5'-cyclic monophosphate (cGMP) levels at a time when contraction was decreasing, but had no influence on adenosine 3',5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin did not elevate cGMP, but rapidly decreased cAMP levels. MIX (1 mM) increased both cAMP and cGMP levels. Oxytocin or methacholine further increased cGMP, indicating activation of guanylate cyclase. Oxytocin- but not methacholine-induced stimulation of guanylate cyclase was abolished in Ca2+-free solution. Oxytocin increased cAMP over the levels produced by MIX alone, whereas methacholine decreased cAMP below the MIX control values; these effects were insensitive to indomethacin. Tissue levels of cGMP and cAMP did not directly correlate with isometric tension. The results also indicate that both oxytocin and methacholine stimulate guanylate cyclase but have opposing effects on adenylate cyclase of rabbit myometrium.

SYNERGISTIC EFFECTS of CYCLIC TENSION and TRANSFORMING GROWTH FACTOR-β1 on the AORTIC VALVE MYOFIBROBLAST

Science.gov (United States)

Merryman, W. David; Lukoff, Howard D.; Long, Rebecca A.; Engelmayr, George C.; Hopkins, Richard A.; Sacks, Michael S.

2007-01-01

Background Phenotypically, the aortic valve interstitial cell (AVIC) is a dynamic myofibroblast, appearing contractile and activated in times of development, disease, and remodeling. The precise mechanism of phenotypic modulation is unclear, but it is speculated that both biomechanical and biochemical factors are influential. Therefore, we hypothesized that isolated and combined treatments of cyclic tension and TGF-β1 would alter the phenotype and subsequent collagen biosynthesis of AVICs in situ. Methods and Results Porcine aortic valve leaflets received 7 and 14 day treatments of 15% cyclic stretch (Tension), 0.5 ng/ml TGF-β1 (TGF), 15% cyclic stretch and 0.5 ng/ml TGF-β1 (Tension+TGF), or neither mechanical nor cytokine stimuli (Null). Tissues were homogenized and assayed for AVIC phenotype (smooth muscle α-actin (SMA)) and collagen biosynthesis (via heat shock protein 47 (Hsp47) which was further verified with type I collagen C-terminal propeptide (CICP)). At both 7 and 14 days, SMA, Hsp47, and CICP quantities were significantly greater (p<0.001) in the Tension+TGF group compared to all other groups. Additionally, Tension alone appeared to maintain SMA and Hsp47 levels that were measured at day 0, while TGF alone elicited an increase in SMA and Hsp47 compared to day 0 levels. Null treatment revealed diminished proteins at both time points. Conclusions Elevated TGF-β1 levels, in the presence of cyclic mechanical tension, resulted in synergistic increases in the contractile and biosynthetic proteins in AVICs. Since cyclic mechanical stimuli can never be relieved in vivo, the presence of TGF-β1 (possibly from infiltrating macrophages) may result in overly biosynthetic AVICs, leading to altered ECM architecture, compromised valve function, and ultimately degenerative valvular disease. PMID:17868877

Cyclic creep-rupture behavior of three high-temperature alloys.

Science.gov (United States)

Halford, G. R.

1972-01-01

Study of some important characteristics of the cyclic creep-rupture curves for the titanium alloy 6Al-2Sn-4Zr-2Mo at 900 and 1100 F (755 and 865 K), the cobalt-base alloy L-605 at 1180 F (910 K), and for two hardness levels of 316 stainless steel at 1300 F (980 K). The cyclic creep-rupture curve relates tensile stress and tensile time-to-rupture for strain-limited cyclic loading and has been found to be independent of the total strain range and the level of compressive stress employed in the cyclic creep-rupture tests. The cyclic creep-rupture curve was always found to be above and to the right of the conventional (constant load) monotonic creep-rupture curve by factors ranging from 2 to 10 in time-to-rupture. This factor tends to be greatest when the creep ductility is large. Cyclic creep acceleration was observed in every cyclic creep-rupture test conducted. The phenomenon was most pronounced at the highest stress levels and when the tensile and compressive stresses were completely reversed. In general, creep rates were found to be lower in compression than in tension for equal true stresses. The differences, however, were strongly material-dependent.

Studies on the production of endogenous pyrogen by rabbit monocytes: the role of calcium and cyclic nucleotides.

Science.gov (United States)

Sigal, S L; Duff, G W; Atkins, E

1985-01-01

Rabbit monocytes stimulated with endotoxin produced endogenous pyrogen, even under conditions of high or low extracellular calcium concentrations. Maximal production occurred when the concentration was in the near-physiological range. Prolonged incubation of cells with a calcium chelator prevented subsequent activation with endotoxin, an effect which was rapidly reversible by re-addition of calcium but not other cations. Addition of small amounts of lanthanum, which acts as a calcium channel blocker, prevented the restoration of pyrogen production, indicating that entry of the added calcium into the monocyte was required. Incorporation of a calcium ionophore into the cell membrane did not stimulate pyrogen production, and no measurable influx or efflux of calcium occurred during stimulation with endotoxin. These observations suggest that a slowly exchangeable calcium pool is necessary for the production of endogenous pyrogen, but that a rise in intracellular calcium is not by itself a necessary or sufficient stimulus. This stands in contrast to other biological systems in which Ca2+ directly couples stimulus and hormone secretion. Incubation of cells with agents shown to increase cyclic 3',5' AMP or cyclic 3',5' GMP levels in monocytes similarly did not stimulate pyrogen production or modulate its production by endotoxin stimulation. Thus, cyclic nucleotides also did not play a detectable role as intracellular messengers in this system. Future work is required to define more clearly the mechanism for the production of endogenous pyrogen, given its marked effects on the immune system through lymphocyte activation and temperature regulation.

Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

Science.gov (United States)

Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

1999-04-01

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

Viral evasion of DNA-stimulated innate immune responses

Science.gov (United States)

Christensen, Maria H; Paludan, Søren R

2017-01-01

Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP–AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway. PMID:26972769

Determination of the usage factor of components after cyclic loading by means of high-resolution microstructural examination

International Nuclear Information System (INIS)

Seibold, A.; Scheibe, A.; Assmann, H.D.

1991-01-01

Materials subjected to cyclic loading experience a change in the microstructure which may affect the service life. Quantification of the microstructural changes and allocation of the microstructural condition to the corresponding point on the fatigue curve for the component material allows the usage factor to be derived. Taking the low-alloy, fine-grained structural steel 20MnMoNi55 (quenched and tempered structure) as an example, the relationship between microstructure and number of load cycles can be represented in the form of a reference curve. High-resolution examination allows the usage factor to be determined up to η=N/N f ≅0.5 under the given cyclic loading. Only a small specimen volume is required for examination using a transmission electron microscope. It can be taken from the component without affecting the required minimum wall thickness. The location of the specimen must, however, be stipulated, e.g. the location of highest loading according to calculations. When removing the specimen, care must be taken to ensure that the micro-structure is not affected. If these requirements are observed, high-resolution microstructural examination provides a method for checking the usage factor of a component. (orig.)

Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

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Hou Ssu-Yu

2010-06-01

Full Text Available Abstract Background 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors (statins have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. Methods The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. Results Simvastatin (20-50 μM exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin. Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2 formation, and phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP phosphorylation, and endothelial nitric oxide synthase (eNOS expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCγ2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. Conclusion The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP-eNOS/NO-cyclic

The Potential Role of Recombinant Hematopoietic Colony-Stimulating Factors in Preventing Infections in the Immunocompromised Host

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James Rusthoven

1991-01-01

Full Text Available Hematopoietic colony-stimulating factors coordinate the proliferation and maturation of bone marrow and peripheral blood cells during normal hematopoiesis. Most of these factors are now available as recombinant human colony-stimulating factors, and preclinical and clinical testing is proceeding rapidly. Granulocyte and granulocyte/macrophage colony-stimulating factors have been the most extensively studied to date. In human clinical trials, granulocyte colony-stimulating factor improves neutrophil counts and function, reduces episodes of febrile neutropenia, improves neutrophil recovery after disease- or treatment-induced myelosuppression, and reduces the number of serious infections in several neutropenic disease states. Granulocyte/macrophage colony-stimulating factor has similar biological properties but may also improve eosinophil proliferation and function, and platelet cell recovery after myelotoxic bone marrow injury, Interleukin-1 boosts the effects of granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor, but also may promote the resolution of established infections in conjunction with antibiotics. The therapeutic realities and future therapeutic implications of these agents for the therapy of infections, cancer and hemopoietic disorders are discussed.

The Cyclicality of New Product Introductions

OpenAIRE

Kostas Axarloglou

2003-01-01

This study analyzes empirically the cyclical nature of the timing of new product introductions in U.S. manufacturing. New product introductions vary more in nonseasonal frequencies than in seasonal frequencies. However, the seasons alone account for only a small part of their total variability with demand factors being much more important. Demand fluctuations account for 35%80% and 17%43%, respectively, of the seasonal and cyclical variability of new product introductions in various industrie...

Factors influencing parental decision making about stimulant treatment for attention-deficit/hyperactivity disorder.

Science.gov (United States)

Ahmed, Rana; McCaffery, Kirsten J; Aslani, Parisa

2013-04-01

Attention-deficit/hyperactivity disorder (ADHD) is a pediatric psychological condition commonly treated with stimulant medications. Negative media reports and stigmatizing societal attitudes surrounding the use of these medications make it difficult for parents of affected children to accept stimulant treatment, despite it being first line therapy. The purpose of this study was to identify factors that influence parental decision making regarding stimulant treatment for ADHD. A systematic review of the literature was conducted to identify studies: 1) that employed qualitative methodology, 2) that highlighted treatment decision(s) about stimulant medication, 3) in which the decision(s) were made by the parent of a child with an official ADHD diagnosis, and 4) that examined the factors affecting the decision(s) made. Individual factors influencing parental treatment decision making, and the major themes encompassing these factors, were identified and followed by a thematic analysis. Eleven studies reporting on the experiences of 335 parents of children with ADHD were included. Four major themes encompassing influences on parents' decisions were derived from the thematic analysis performed: confronting the diagnosis, external influences, apprehension regarding therapy, and experience with the healthcare system. The findings of this systematic review reveal that there are multiple factors that influence parents' decisions about stimulant therapy. This information can assist clinicians in enhancing information delivery to parents of children with ADHD, and help reduce parental ambivalence surrounding stimulant medication use. Future work needs to address parental concerns about stimulants, and increase their involvement in shared decision making with clinicians to empower them to make the most appropriate treatment decision for their child.

Factors influencing breeding success, ovarian cyclicity, and cub survival in zoo-managed tigers (Panthera tigris).

Science.gov (United States)

Saunders, Sarah P; Harris, Tara; Traylor-Holzer, Kathy; Beck, Karen Goodrowe

2014-01-10

Understanding factors that influence reproduction and offspring survival in zoo populations is critical for management of threatened and endangered species. Examination of long-term data (1989-2011) compiled from the Association of Zoos and Aquarium's zoo-managed tiger breeding program provides the basis for a more thorough understanding of reproduction and scientifically based decisions for effective population management in this endangered felid. Biological and management-related factors that could influence tiger breeding success and cub survival were evaluated using logistic mixed models. Breeding success improved with female age until approximately age five, then declined thereafter. Experienced female breeders had greater breeding success than inexperienced females. Litter size was most predictive of cub survival, with average-sized litters (3-4 cubs) experiencing the highest proportional survival. Management-related factors, such as whether the breeding institution had a recent tiger litter and whether both animals were already located at the same institution, also influenced breeding success and cub survival. These results highlight the importance of institutional husbandry experience and the need to retain knowledge through staff turnovers to achieve optimal reproductive success. Using fecal estrogen data, frequency of ovarian cyclicity and mean cycle length did not differ by female age or parity; thus, lack of cyclicity and/or increased cycle duration are not likely explanations for declining breeding success with age. These results provide valuable reproductive information that should improve scientific management of zoo-based tiger populations. Copyright © 2013 Elsevier B.V. All rights reserved.

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

International Nuclear Information System (INIS)

Brady, Robert T.; O'Brien, Fergal J.; Hoey, David A.

2015-01-01

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Energy Technology Data Exchange (ETDEWEB)

Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

2015-03-27

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Colony stimulating factors and their clinical implication

International Nuclear Information System (INIS)

Asano, Shigetaka

1989-01-01

Granulocytes and macrophage are dependent for their production and/or functional activation in vitro on the presence of a family of glycoproteins. They are generally called colony-stimulating factors (CSFs) because of their capacity to stimulate colony formation in semi-solid cultures, and are currently classified into four distinct subtypes, that is, Multi-CSF, GM-CSF, G-CSF and M-CSF, according to the cell type of colonies formed under their stimulation or their target cell specificity. All of the murine and human CSF subtypes and the genes for them have become available in a purified form and in a large scale, and now allow us to investigate their interactions, the mechanisms for their actions, the cell-cell interactions leading to their production and secretion, and their actions in vivo. Furthermore, the preclinical and/or clinical studies which were carried out using the purified CSFs strongly indicate that human CSFs will be effective strategies for preventing and treating opportunistic bacterial and fungal infection as a major cause of death in granulocytopenic patients. (author)

Thapsigargin defines the roles of cellular calcium in secretagogue-stimulated enzyme secretion from pancreatic acini.

Science.gov (United States)

Metz, D C; Patto, R J; Mrozinski, J E; Jensen, R T; Turner, R J; Gardner, J D

1992-10-15

In the present study we used thapsigargin (TG), an inhibitor of microsomal calcium ATPase, to evaluate the roles of free cytoplasmic calcium and intracellular stored calcium in secretagogue-stimulated enzyme secretion from rat pancreatic acini. Using microspectrofluorimetry of fura-2-loaded pancreatic acini, we found that TG caused a sustained increase in free cytoplasmic calcium by mobilizing calcium from inositol 1,4,5-trisphosphate-sensitive intracellular stores and by increasing influx of extracellular calcium. TG also caused a small increase in basal amylase secretion, inhibited the stimulation of amylase secretion caused by secretagogues that increase inositol 1,4,5-trisphosphate, and potentiated the stimulation of amylase secretion caused by 12-O-tetradecanoylphorbol-13-acetate or secretagogues that increase cyclic adenosine 3',5'-monophosphate. Bombesin, which like TG increased free cytoplasmic calcium, also potentiated the stimulation of amylase secretion caused by secretagogues that increase cyclic adenosine 3',5'-monophosphate, but did not inhibit the stimulation of amylase secretion caused by secretagogues that increase inositol 1,4,5-trisphosphate. Finally, TG inhibited the sustained phase of cholecystokinin-stimulated amylase secretion and potentiated the time course of vasoactive intestinal peptide-stimulated amylase secretion. The present findings indicate that stimulation of amylase secretion by secretagogues that increase inositol 1,4,5-trisphosphate does not depend on increased free cytoplasmic calcium per se. In contrast, TG-induced potentiation of the stimulation of secretagogues that increase cellular cyclic adenosine 3',5'-monophosphate appears to result from increased free cytoplasmic calcium per se.

INNOVATIONn#8211; AN INFLUENCE FACTOR OF CYCLICAL FLUCTUATIONS. STUDY CASE FOR ROMANIA, BETWEEN 1995 AND 2009

Directory of Open Access Journals (Sweden)

Cismaº Laura Mariana

2012-07-01

Full Text Available The study of influence factors of cyclical fluctuations is of major importance for a countryn#8217;s economy. In the present context, of the new economy, where the emphasis is on new technologies, and information is the main product and resource of the economy, innovation is one of the most important factors among the ones which influence the economic activity fluctuations. As part of a larger paper, this study is set to emphasize and explain the influence of innovation on the cyclical fluctuations in Romania between 1995 and 2009. The following analysis indicators were used: the n#8216;innovationn#8217; factor is represented by Research n Development expenses and by the number of people with internet access, whereas the economic activity fluctuations are represented by the fluctuations in the real GDP. The research starts with the conceptual boundaries regarding innovation, with an emphasis on Joseph Schumpetern#8217;s theory, then, the influence of innovation on economic activity fluctuations is underlined through a quantitative analysis of the three indicators mentioned above and through an econometric model. The results of the research underline Romanian#8217;s economic status, the scale on which new technologies have entered the Romanian market and the way in which the fluctuations of the economic activity are closely linked to innovation.

Chenodeoxycholic acid stimulated fibroblast growth factor 19 response

DEFF Research Database (Denmark)

Borup, C; Wildt, S; Rumessen, J J

2017-01-01

BACKGROUND: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. AIM: To explore if an impaired FGF19 response identifies primary bile acid...

Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes

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Carbone Maria

2006-09-01

Full Text Available Abstract Background Mammalian sperm-oocyte interaction at fertilization involves several combined interactions between integrins on the oocyte and integrin ligands (disintegrins on the sperm. Recent research has indicated the ability of peptides containing the RGD sequence that characterized several sperm disintegrins, to induce intracellular Ca2+ transients and to initiate parthenogenetic development in amphibian and bovine oocytes. In the present study, we investigate the hypothesis that an integrin-associated signalling may participate in oocyte activation signalling by determining the ability of a cyclic RGD-containing peptide to stimulate the activation of protein kinase C (PKC and the exocytosis of cortical granules in mouse oocytes. Methods An In-Vitro-Fertilization assay (IVF was carried in order to test the condition under which a peptide containing the RGD sequence, cyclo(Arg-Gly-Asp-D-Phe-Val, was able to inhibit sperm fusion with zona-free mouse oocytes at metaphase II stage. PKC activity was determined by means of an assay based on the ability of cell lysates to phosphorylate MARKS peptide, a specific PKC substrate. Loss of cortical granules was evaluated by measuring density in the oocyte cortex of cortical granules stained with LCA-biotin/Texas red-streptavidin. In all the experiments, effects of a control peptide containing a non RGD sequence, cyclo(Arg-Ala-Asp-D-Phe-Val, were evaluated. Results The IVF assay revealed that the fusion rate declined significantly when insemination was carried out in the presence of cyclic RGD peptide at concentrations > or = 250 microM (P Conclusion The presents results provide evidence that a cyclic RGD peptide highly effective in inhibiting sperm-oocyte interaction stimulates in mouse oocytes the activation of PKC and the exocytosis of cortical granules. These data support the view that RGD-binding receptors may function as signalling receptors giving rise integrated signalling not sufficient for

Evidence for a Messenger Function of Cyclic GMP During Phosphodiesterase Induction in Dictyostelium discoideum

NARCIS (Netherlands)

Haastert, Peter J.M. van; Pasveer, Frank J.; Meer, Rob C. van der; Heijden, Paul R. van der; Walsum, Hans van; Konijn, Theo M.

1982-01-01

Chemotactic stimulation of vegetative or aggregative Dictyostelium discoideum cells induced a transient elevation of cyclic GMP levels. The addition of chemoattractants to postvegetative cells by pulsing induced phosphodiesterase activity. The following lines of evidence suggest a messenger function

Gc protein-derived macrophage-activating factor (GcMAF) stimulates cAMP formation in human mononuclear cells and inhibits angiogenesis in chick embryo chorionallantoic membrane assay.

Science.gov (United States)

Pacini, Stefania; Morucci, Gabriele; Punzi, Tiziana; Gulisano, Massimo; Ruggiero, Marco

2011-04-01

The effects of Gc protein-derived macrophage-activating factor (GcMAF) have been studied in cancer and other conditions where angiogenesis is deregulated. In this study, we demonstrate for the first time that the mitogenic response of human peripheral blood mononuclear cells (PBMCs) to GcMAF was associated with 3'-5'-cyclic adenosine monophosphate (cAMP) formation. The effect was dose dependent, and maximal stimulation was achieved using 0.1 ng/ml. Heparin inhibited the stimulatory effect of GcMAF on PBMCs. In addition, we demonstrate that GcMAF (1 ng/ml) inhibited prostaglandin E(1)- and human breast cancer cell-stimulated angiogenesis in chick embryo chorionallantoic membrane (CAM) assay. Finally, we tested different GcMAF preparations on CAM, and the assay proved to be a reliable, reproducible and inexpensive method to determine the relative potencies of different preparations and their stability; we observed that storage at room temperature for 15 days decreased GcMAF potency by about 50%. These data could prove useful for upcoming clinical trials on GcMAF.

Specificity of the Cyclic GMP-Binding Activity and of a Cyclic GMP-Dependent Cyclic GMP Phosphodiesterase in Dictyostelium discoideum

NARCIS (Netherlands)

Haastert, Peter J.M. van; Walsum, Hans van; Meer, Rob C. van der; Bulgakov, Roman; Konijn, Theo M.

1982-01-01

The nucleotide specificity of the cyclic GMP-binding activity in a homogenate of Dictyostelium discoideum was determined by competition of cyclic GMP derivatives with [8-3H] cyclic GMP for the binding sites. The results indicate that cyclic GMP is bound to the binding proteins by hydrogen bonds at

Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor

OpenAIRE

Hata, Yasuaki; Clermont, Allen Charles; Yamauchi, Teruaki; Pierce, Eric Adam; Suzuma, Izumi; Kagokawa, Hiroyuki; Yoshikawa, Hiroshi; Robinson, Gregory S.; Ishibashi, Tatsuro; Hashimoto, Toshihiko; Umeda, Fumio; Bursell, Sven E.; Aiello, Lloyd Paul

2000-01-01

Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have examined the expression, regulation, and hemodynamic bioactivity of PSF both in whole retina and in cultured cells derived from this tissue. PSF was expressed in all retinal cell types examined in vitro, but immunohistochemical analysis revealed PSF mainly associated with retinal vessels. PSF expression was constitutive in retinal pericy...

Cafestol Inhibits Cyclic-Strain-Induced Interleukin-8, Intercellular Adhesion Molecule-1, and Monocyte Chemoattractant Protein-1 Production in Vascular Endothelial Cells

Science.gov (United States)

Hao, Wen-Rui; Sung, Li-Chin; Chen, Chun-Chao; Chen, Jin-Jer

2018-01-01

Moderate coffee consumption is inversely associated with cardiovascular disease mortality; however, mechanisms underlying this causal effect remain unclear. Cafestol, a diterpene found in coffee, has various properties, including an anti-inflammatory property. This study investigated the effect of cafestol on cyclic-strain-induced inflammatory molecule secretion in vascular endothelial cells. Cells were cultured under static or cyclic strain conditions, and the secretion of inflammatory molecules was determined using enzyme-linked immunosorbent assay. The effects of cafestol on mitogen-activated protein kinases (MAPK), heme oxygenase-1 (HO-1), and sirtuin 1 (Sirt1) signaling pathways were examined using Western blotting and specific inhibitors. Cafestol attenuated cyclic-strain-stimulated intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein- (MCP-) 1, and interleukin- (IL-) 8 secretion. Cafestol inhibited the cyclic-strain-induced phosphorylation of extracellular signal-regulated kinase and p38 MAPK. By contrast, cafestol upregulated cyclic-strain-induced HO-1 and Sirt1 expression. The addition of zinc protoporphyrin IX, sirtinol, or Sirt1 silencing (transfected with Sirt1 siRNA) significantly attenuated cafestol-mediated modulatory effects on cyclic-strain-stimulated ICAM-1, MCP-1, and IL-8 secretion. This is the first study to report that cafestol inhibited cyclic-strain-induced inflammatory molecule secretion, possibly through the activation of HO-1 and Sirt1 in endothelial cells. The results provide valuable insights into molecular pathways that may contribute to the effects of cafestol. PMID:29854096

Mapping reservoir volume changes during cyclic steam stimulation using tiltmeter-based surface deformation measurements

Energy Technology Data Exchange (ETDEWEB)

Du, J.; Davis, E.J.; Roadarmel, W.H.; Wolhart, S.L.; Marsic, S.; Gusek, R.; Wright, C.A. [Society of Petroleum Engineers, Richardson, TX (United States)]|[Pinnacle Technologies Inc., Houston, TX (United States); Brissenden, S.J.; McGillivray, P. [Shell Canada Ltd., Calgary, AB (Canada). Calgary Research Centre; Bourne, S.; Hofstra, P. [Shell International E and P, Calgary, AB (Canada)

2005-11-01

Surface deformation measurements have been effectively used to monitor production, waterflooding, waste injection and steam flooding in oil fields, and in cyclic steam stimulation (CSS) applications. It was shown that further information can be obtained from this technique by inverting the surface deformation for the volumetric deformation at the reservoir level, so that the aerial distribution of volumetric distribution can be identified. A poroelastic model calculated deformation resulting from volumetric changes in the reservoir. A linear geophysical model was then formulated to invert the reservoir volumetric deformation from the measured surface deformation. Constraints were applied to resolve the inversion problem. Theoretical surface deformation was calculated after each inversion from the inverted volumetric deformation distribution which best fit the measured information data, or tilt, at the surface. The technique was then applied to real data from a CSS injection project at Shell Canada's Peace River development in northern Alberta, where several pads of horizontal wells have been developed. A total of 50 tiltmeters were used to monitor half of Pad A and 70 tiltmeters were used to monitor Pad B. Monitoring was used to identify and characterize any hydraulic fracturing that was contributing to injection mechanisms in the reservoir. It was noted that inverting the measured surface tilt for the volumetric change at reservoir levels improved the ability to interpret reservoir processes. It was observed that volumetric changes can be non-uniform with some pad areas deforming more than others. It was concluded that deformation-based, reservoir-level monitoring has proven helpful in ongoing efforts to optimize such variables as the length of well laterals, injection rates, lateral spacing and cycle times. 10 refs., 32 figs.

Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cyclic rats after low-dose endotoxin infusion

NARCIS (Netherlands)

Faas, MM; Bakker, WW; Valkhof, N; Baller, JFW; Schuiling, GA

Plasma endothelin-1 and tumor necrosis factor-alpha were determined in pregnant and cyclic rats after infusion of either endotoxin (1.0 mu g/kg of body weight) or saline solution. After endotoxin, but not after saline solution, administration there was a transient endothelin-1 response in pregnant

Fatigue crack growth behavior under cyclic thermal transient stress

International Nuclear Information System (INIS)

Ueda, Masahiro; Kano, Takashi; Yoshitoshi, Atsushi.

1986-01-01

Thermal fatigue tests were performed using straight pipe specimens subjected to cyclic thermal shocks of liquid sodium, and crack growth behaviors were estimated using striation patterns observed clearly on any crack surface. Crack growth rate under cyclic thermal strain reaches the maximum at one depth, and after that it decreases gradually with crack depth. The peak location of crack growth rate becomes deeper by superposition of constant primary stress. Parallel cracks co-existing in the neighborhood move the peak to shallower location and decrease the maximum crack growth rate. The equivalent stress intensity factor range calculated by Walker's formula is successfully applied to the case of negative stress ratio. Fatigue crack growth rate under cyclic thermal strain agreed well with that under the constant temperature equal to the maximum value in the thermal cycle. Simplified methods for calculating the stress intensity factor and the crack interference factor have been developed. Crack growth behavior under thermal fatigue could be well predicted using numerical analysis results. (author)

Fatigue crack growth behavior under cyclic transient thermal stress

International Nuclear Information System (INIS)

Ueda, Masahiro; Kano, Takashi; Yoshitoshi, Atsushi.

1987-01-01

Thermal fatigue tests were performed using straight pipe specimens subjected to cyclic thermal shocks of liquid sodium, and crack growth behaviors were estimated using striation patterns observed clearly on any crack surface. Crack growth rate under cyclic thermal strain reaches the maximum at one depth, and after that it decreases gradually with crack depth. The peak location of crack growth rate becomes deeper by superposition of constant primary stress. Parallel cracks co-existing in the neighborhood move the peak to shallower location and decrease the maximum crack growth rate. The equivalent stress intensity factor range calculated by Walker's formula is successfully applied to the case of negative stress ratio. Fatigue crack growth rate under cyclic thermal strain agreed well with that under the constant temperature equal to the maximum value in the thermal cycle. Simplified methods for calculating the stress intensity factor and the crack interference factor have been developed. Crack growth behavior under thermal fatigue could be well predicted using numerical analysis results. (author)

Factors influencing the effects of repetitive transcranial magnetic stimulation in Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Na Ye; Tao Feng

2016-01-01

Barker first used transcranial magnetic stimulation in 1985 in human brain function research. Since then, it has gradually been developed into a secure and non-invasive treatment method for neurological diseases. In 1994, Pascual Leone first used it for the treatment of Parkinson's disease (PD) and observed an improvement in the motor symptoms of most of the patients. Recent studies have confirmed that both motor and non-motor symptoms of patients with PD could be improved through biochemical, electrophysiological, and functional magnetic resonance imaging analysis. Different therapeutic applications can be achieved by adjusting the stimulation parameters. Physical factors affecting the therapeutic effect include the shape and size of the coil, array orientation, materials and intensity, frequency of stimulus, etc.; the biological factors include stimulating targets, baseline, circadian rhythms, cerebral cortex thickness, and so on. This paper will review these factors and provide a reference for future research.

Stimulation of cyclic GMP efflux in human melanocytes by hypergravity generated by centrifugal acceleration

NARCIS (Netherlands)

Ivanova, Krassimira; Zadeh, Nahid Hamidi; Block, Ingrid; Das, Pranab K.; Gerzer, Rupert

2004-01-01

Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic

The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP

DEFF Research Database (Denmark)

Almblad, Henrik; Harrison, Joe J; Rybtke, Morten

2015-01-01

infection give rise to rugose small colony variants (RSCVs), which are hyper-biofilm-forming mutants that commonly possess mutations that increase production of the biofilm-promoting secondary messenger cyclic di-GMP (c-di-GMP). We show that RSCVs display a decreased production of acute virulence factors...... as a direct result of elevated c-di-GMP content. Overproduction of c-di-GMP causes a decrease in the transcription of virulence factor genes that are regulated by the global virulence regulator Vfr. The low level of Vfr-dependent transcription is caused by a low level of its coactivator, cyclic AMP (c......AMP), which is decreased in response to a high level of c-di-GMP. Mutations that cause reversion of the RSCV phenotype concomitantly reactivate Vfr-cAMP signaling. Attempts to uncover the mechanism underlying the observed c-di-GMP-mediated lowering of cAMP content provided evidence that it is not caused...

Creep crack growth by grain boundary cavitation under monotonic and cyclic loading

Science.gov (United States)

Wen, Jian-Feng; Srivastava, Ankit; Benzerga, Amine; Tu, Shan-Tung; Needleman, Alan

2017-11-01

Plane strain finite deformation finite element calculations of mode I crack growth under small scale creep conditions are carried out. Attention is confined to isothermal conditions and two time histories of the applied stress intensity factor: (i) a monononic increase to a plateau value subsequently held fixed; and (ii) a cyclic time variation. The crack growth calculations are based on a micromechanics constitutive relation that couples creep deformation and damage due to grain boundary cavitation. Grain boundary cavitation, with cavity growth due to both creep and diffusion, is taken as the sole failure mechanism contributing to crack growth. The influence on the crack growth rate of loading history parameters, such as the magnitude of the applied stress intensity factor, the ratio of the applied minimum to maximum stress intensity factors, the loading rate, the hold time and the cyclic loading frequency, are explored. The crack growth rate under cyclic loading conditions is found to be greater than under monotonic creep loading with the plateau applied stress intensity factor equal to its maximum value under cyclic loading conditions. Several features of the crack growth behavior observed in creep-fatigue tests naturally emerge, for example, a Paris law type relation is obtained for cyclic loading.

Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

Science.gov (United States)

Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

2015-02-01

Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alternative splicing and expression of the insulin-like growth factor (IGF-1) gene in osteoblasts under mechanical stretch

Institute of Scientific and Technical Information of China (English)

XIAN Chengyu; WANG Yuanliang; ZHANG Bingbing; TANG Liling; PAN Jun; LUO Yanfeng; JIANG Peng; LI Dajun

2006-01-01

Insulin-like growth factor 1 (IGF-1) promotes osteoblasts differentiation and bone formation,and its expression is induced by mechanical stretch,thus IGF-1 has been considered an effector molecule that links mechanical stimulation and local tissue responses. In this study, a mechanical stretching device was designed to apply physiological level static or cyclic stretching stimulation to osteoblasts.Different isoforms of IGF-1 mRNA were amplified by RT-PCR from the cells using respective primers and these amplified products were sequenced. An isoform of IGF-1 splicing product was found to be selectively produced by osteoblasts under stretching stimulation. This IGF-1 isoform had identical sequence with the mechano growth factor (MGF) which was originally identified in muscle cells. Regulations of the expression of the liver-type IGF (L.IGF-1) and MGF in osteoblasts under stretch stimulation were further studied using semi-quantitative RT-PCR.Stretch stimulation was found to promot the expression of IGF-1 (L.IGF-1 and MGF), and for both isoforms expression was more effectively stimulated by cyclic stretch than static stretch. MGF was detected only in osteoblasts subjected to mechanical stretch,suggesting MGF was a stretch sensitive growth factor.Expression of MGF peaked earlier than that of L.IGF-1, which was similar to their regulation in muscie and suggested similar roles of MGF and L.IGF-1in bone as in muscle cells. The functions of MGF and L.IGF-1 in osteoblasts shall be established by further experimental studies.

Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

International Nuclear Information System (INIS)

Jones, S.B.; Halenda, S.P.; Bylund, D.B.

1991-01-01

The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism

Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

Energy Technology Data Exchange (ETDEWEB)

Jones, S.B.; Halenda, S.P.; Bylund, D.B. (Univ. of Missouri-Columbia (USA))

1991-02-01

The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism.

Cyclic multiverses

Science.gov (United States)

Marosek, Konrad; Dąbrowski, Mariusz P.; Balcerzak, Adam

2016-09-01

Using the idea of regularization of singularities due to the variability of the fundamental constants in cosmology we study the cyclic universe models. We find two models of oscillating and non-singular mass density and pressure (`non-singular' bounce) regularized by varying gravitational constant G despite the scale factor evolution is oscillating and having sharp turning points (`singular' bounce). Both violating (big-bang) and non-violating (phantom) null energy condition models appear. Then, we extend this idea on to the multiverse containing cyclic individual universes with either growing or decreasing entropy though leaving the net entropy constant. In order to get an insight into the key idea, we consider the doubleverse with the same geometrical evolution of the two `parallel' universes with their physical evolution [physical coupling constants c(t) and G(t)] being different. An interesting point is that there is a possibility to exchange the universes at the point of maximum expansion - the fact which was already noticed in quantum cosmology. Similar scenario is also possible within the framework of Brans-Dicke theory where varying G(t) is replaced by the dynamical Brans-Dicke field φ(t) though these theories are slightly different.

Granulocyte colony-stimulating factor induces in vitro lymphangiogenesis

International Nuclear Information System (INIS)

Lee, Ae Sin; Kim, Dal; Wagle, Susbin Raj; Lee, Jung Eun; Jung, Yu Jin; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

2013-01-01

Highlights: •G-CSF induces tube formation, migration and proliferation of lymphatic cells. •G-CSF increases phosphorylation of MAPK and Akt in lymphatic endothelial cells. •MAPK and Akt pathways are linked to G-CSF-induced in vitro lymphangiogenesis. •G-CSF increases sprouting of a lymphatic ring. •G-CSF produces peritoneal lymphangiogenesis. -- Abstract: Granulocyte-colony stimulating factor (G-CSF) is reported to induce differentiation in cells of the monocyte lineage and angiogenesis in vascular endothelial cells, but its effects on lymphangiogenesis is uncertain. Here we examined the effects and the mechanisms of G-CSF-induced lymphangiogenesis using human lymphatic endothelial cells (hLECs). Our results showed that G-CSF induced capillary-like tube formation, migration and proliferation of hLECs in a dose- and time-dependent manner and enhanced sprouting of thoracic duct. G-CSF increased phosphorylation of Akt and ERK1/2 in hLECs. Supporting the observations, specific inhibitors of phosphatidylinositol 3′-kinase and MAPK suppressed the G-CSF-induced in vitro lymphangiogenesis and sprouting. Intraperitoneal administration of G-CSF to mice also stimulated peritoneal lymphangiogenesis. These findings suggest that G-CSF is a lymphangiogenic factor

Cyclic tensile strain enhances human mesenchymal stem cell Smad 2/3 activation and tenogenic differentiation in anisotropic collagen-glycosaminoglycan scaffolds

Directory of Open Access Journals (Sweden)

WK Grier

2017-03-01

Full Text Available Orthopaedic injuries, particularly those involving ligaments and tendons, are some of the most commonly treated ailments in the United States and are associated with both high costs and poor outcomes. Regenerative medicine strategies for tendon injuries could be enhanced by three-dimensional biomaterials that can promote cell alignment and pro-tenogenic differentiation of patient-derived MSCs. We have previously described a collagen-glycosaminoglycan (CG scaffold possessing aligned structural features able to promote bone marrow MSC differentiation towards a tenogenic lineage, in the absence of growth factor supplementation. We aimed to employ a bioreactor to enhance MSC tenogenic differentiation within the aligned CG scaffold via cyclic tensile strain (CTS, and further to evaluate the relative effects of strain cycle duration and extended application of repeated cycles of CTS on MSC response. Human MSCs were cultured in CG scaffolds for up to 6 d under static (unloaded or cyclic tensile strain (1 Hz for 10 min every 6 h. Time-dependent activation of ERK 1/2 and p38 mechanotransduction pathways was observed within each 6 h strain cycle. MSCs remained viable throughout the experiment and application of CTS robustly upregulated the expression of tendon-specific extracellular matrix proteins and phenotypic markers. Simultaneously, CTS promoted increased phosphorylation of Smad 2/3, suggesting a link between tensile stimulation and TGF-β family growth factor production. Together, we demonstrated the design, fabrication and validation of a high-throughput tensile stimulation bioreactor to increase MSC tenogenic differentiation in porous CG scaffolds.

Explanation of application standards of hematopoietic stimulating factors in the treatment of acute radiation sickness

International Nuclear Information System (INIS)

Xing Zhiwei; Jiang Enhai; Wang Guilin; Luo Qingliang

2012-01-01

Occupational standard of the Ministry of health-Application Standards of Hematopoietic Stimulating Factors in the Treatment of Acute Radiation Sickness has been completed as a draft standard. Based on the wide study and analysis of related animal experimental literature about hematopoietic stimulating factor in the treatment of acute radiation sickness and domestic and foreign clinical reports about application of hematopoietic stimulating factor in radiation accidents in the past decade, the standard was enacted according to the suggestions of International Atomic Energy Agency and the United States Strategic National Stockpile Radiation Working Group and European countries about the application of hematopoietic stimulating factor. It is mainly used for nuclear accident emergency and the treatment of the bone marrow form of acute radiation sickness caused by radiation accidents. It also applies to other hematopoietic failure diseases. In order to implement this standard correctly, the relevant contents of the standard were interpreted in this article. (authors)

Performance study of Ke factors in simplified elastic plastic fatigue analyses with emphasis on thermal cyclic loading

International Nuclear Information System (INIS)

Lang, Hermann; Rudolph, Juergen; Ziegler, Rainer

2011-01-01

As code-based fully elastic plastic code conforming fatigue analyses are still time consuming, simplified elastic plastic analysis is often applied. This procedure is known to be overly conservative for some conditions due to the applied plastification (penalty) factor K e . As a consequence, less conservative fully elastic plastic fatigue analyses based on non-linear finite element analyses (FEA) or simplified elastic plastic analysis based on more realistic K e factors have to be used for fatigue design. The demand for more realistic K e factors is covered as a requirement of practical fatigue analysis. Different code-based K e procedures are reviewed in this paper with special regard to performance under thermal cyclic loading conditions. Other approximation formulae such as those by Neuber, Seeger/Beste or Kuehnapfel are not evaluated in this context because of their applicability to mechanical loading excluding thermal cyclic loading conditions typical for power plant operation. Besides the current code-based K e corrections, the ASME Code Case N-779 (e.g. Adam's proposal) and its modification in ASME Section VIII is considered. Comparison of elastic plastic results and results from the Rules for Nuclear Facility Components and Rules for Pressure Vessels reveals a considerable overestimation of usage factor in the case of ASME III and KTA 3201.2 for the examined examples. Usage factors according to RCC-M, Adams (ASME Code Case N-779), ASME VIII (alternative) and EN 13445-3 are essentially comparable and less conservative for these examples. The K v correction as well as the applied yield criterion (Tresca or von Mises) essentially influence the quality of the more advanced plasticity corrections (e.g. ASME Code Case N-779 and RCC-M). Hence, new proposals are based on a refined K v correction.

Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.

Science.gov (United States)

Hwang, Ji-Sun; Jung, Eun-Hye; Kwon, Mi-Youn; Han, Inn-Oc

2016-09-15

We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment. Copyright © 2016. Published by Elsevier B.V.

Factors influencing the effects of repetitive transcranial magnetic stimulation in Parkinson’s disease

Institute of Scientific and Technical Information of China (English)

Na Ye; Tao Feng

2016-01-01

Barker first used transcranial magnetic stimulation in 1985 in human brain function research. Since then, it has gradually been developed into a secure and non-invasive treatment method for neurological diseases. In 1994, Pascual Leone first used it for the treatment of Parkinson’s disease(PD) and observed an improvement in the motor symptoms of most of the patients. Recent studies have confirmed that both motor and non-motor symptoms of patients with PD could be improved through biochemical, electrophysiological, and functional magnetic resonance imaging analysis. Different therapeutic applications can be achieved by adjusting the stimulation parameters.Physical factors affecting the therapeutic effect include the shape and size of the coil, array orientation, materials and intensity, frequency of stimulus, etc.; the biological factors include stimulating targets, baseline, circadian rhythms, cerebral cortex thickness, and so on. This paper will review these factors and provide a reference for future research.

Cyclic olefin copolymer-silica nanocomposites foams

Czech Academy of Sciences Publication Activity Database

Pegoretti, A.; Dorigato, A.; Biani, A.; Šlouf, Miroslav

2016-01-01

Roč. 51, č. 8 (2016), s. 3907-3916 ISSN 0022-2461 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : cyclic olefin copolymer * nanocomposites * silica Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.599, year: 2016

The role of anti-cyclic citrullinated peptide antibodies in predicting rheumatoid arthritis.

Science.gov (United States)

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Tafaj, Argjend; Izairi, Remzi; Rexhepi, Blerta

2011-01-01

The study presents the results of predicting role of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis, compared to rheumatoid factor. 32 patients with rheumatoid arthritis were identified from a retrospective chart review. The results of our study show that presence of the rheumatoid factor has less diagnostic and prognostic significance than the anti-cyclic citrullinated peptide, and suggests its superiority in predicting an erosive disease course.

Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

International Nuclear Information System (INIS)

Hu, Jiang-Tian; Li, Yan; Yu, Bing; Gao, Guo-Jie; Zhou, Ting; Li, Song

2015-01-01

To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces

Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

Energy Technology Data Exchange (ETDEWEB)

Hu, Jiang-Tian; Li, Yan; Yu, Bing; Gao, Guo-Jie; Zhou, Ting; Li, Song, E-mail: song_li59@126.com

2015-08-21

To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces.

DNA-Mediated Cyclic GMP-AMP Synthase-Dependent and -Independent Regulation of Innate Immune Responses.

Science.gov (United States)

Motani, Kou; Ito, Shinji; Nagata, Shigekazu

2015-05-15

Cytoplasmic DNA activates cyclic GMP-AMP synthase (cGAS) to produce cyclic 2'-5'3'-5'GMP-AMP dinucleotide (2'5 'cGAMP). The binding of 2'5'cGAMP to an adaptor protein, stimulator of IFN genes (STING), activates a transcription factor, IFN regulatory factor 3, leading to the induction of IFN and chemokine gene expression. In this study, we found that the 2'5'cGAMP-dependent STING activation induced highly upregulated CXCL10 gene expression. Formation of a distinct STING dimer, which was detected by native PAGE, was induced by 2'5'cGAMP, but not 3'-5'3'-5'cGAMP. Analysis of DNase II(-/-) mice, which constitutively produce IFN-β and CXCL10, showed the accumulation of 2'5'cGAMP in their fetal livers and spleens, suggesting that the undigested DNA accumulating in DNase II(-/-) cells may have leaked from the lysosomes into the cytoplasm. The DNase II(-/-) mouse embryonic fibroblasts produced 2'5'cGAMP in a cGAS-dependent manner during apoptotic cell engulfment. However, cGAS deficiency did not impair the STING-dependent upregulation of CXCL10 in DNase II(-/-) mouse embryonic fibroblasts that was induced by apoptotic cell engulfment or DNA lipofection. These results suggest the involvement of a cGAS-independent additional DNA sensor(s) that induces the STING-dependent activation of innate immunity. Copyright © 2015 by The American Association of Immunologists, Inc.

Comparative assessment of cyclic J-R curve determination by different methods in a pressure vessel steel

Energy Technology Data Exchange (ETDEWEB)

Chowdhury, Tamshuk, E-mail: tamshuk@gmail.com [Deep Sea Technologies, National Institute of Ocean Technology, Chennai, 600100 (India); Sivaprasad, S.; Bar, H.N.; Tarafder, S. [Fatigue & Fracture Group, Materials Science and Technology Division, CSIR-National Metallurgical Laboratory, Jamshedpur, 831007 (India); Bandyopadhyay, N.R. [School of Materials Science and Engineering, Indian Institute of Engineering, Science and Technology, Shibpur, Howrah, 711103 (India)

2016-04-15

Cyclic J-R behaviour of a reactor pressure vessel steel using different methods available in literature has been examined to identify the best suitable method for cyclic fracture problems. Crack opening point was determined by moving average method. The η factor was experimentally determined for cyclic loading conditions and found to be similar to that of ASTM value. Analyses showed that adopting a procedure analogous to the ASTM standard for monotonic fracture is reasonable for cyclic fracture problems, and makes the comparison to monotonic fracture results straightforward. - Highlights: • Different methods of cyclic J-R evaluation compared. • A moving average method for closure point proposed. • η factor for cyclic J experimentally validated. • Method 1 is easier, provides a lower bound and direct comparison to monotonic fracture.

Uniaxial cyclic strain enhances adipose-derived stem cell fusion with skeletal myocytes

Energy Technology Data Exchange (ETDEWEB)

Andersen, Jens Isak; Juhl, Morten; Nielsen, Thøger; Emmersen, Jeppe; Fink, Trine; Zachar, Vladimir; Pennisi, Cristian Pablo, E-mail: cpennisi@hst.aau.dk

2014-07-25

Highlights: • Uniaxial cyclic tensile strain (CTS) applied to ASCs alone or in coculture with myogenic precursors. • CTS promoted the formation of a highly ordered array of parallel ASCs. • Without biochemical supplements, CTS did not support advanced myogenic differentiation of ASCs. • Mechanical stimulation of cocultures boosted fusion of ASCs with skeletal myoblasts. - Abstract: Although adult muscle tissue possesses an exceptional capacity for regeneration, in the case of large defects, the restoration to original state is not possible. A well-known source for the de novo regeneration is the adipose-derived stem cells (ASCs), which can be readily isolated and have been shown to have a broad differentiation and regenerative potential. In this work, we employed uniaxial cyclic tensile strain (CTS), to mechanically stimulate human ASCs to participate in the formation skeletal myotubes in an in vitro model of myogenesis. The application of CTS for 48 h resulted in the formation of a highly ordered array of parallel ASCs, but failed to support skeletal muscle terminal differentiation. When the same stimulation paradigm was applied to cocultures with mouse skeletal muscle myoblasts, the percentage of ASCs contributing to the formation of myotubes significantly exceeded the levels reported in the literature hitherto. In perspective, the mechanical strain may be used to increase the efficiency of incorporation of ASCs in the skeletal muscles, which could be found useful in diverse traumatic or pathologic scenarios.

On the equivalence of cyclic and quasi-cyclic codes over finite fields

Directory of Open Access Journals (Sweden)

Kenza Guenda

2017-07-01

Full Text Available This paper studies the equivalence problem for cyclic codes of length $p^r$ and quasi-cyclic codes of length $p^rl$. In particular, we generalize the results of Huffman, Job, and Pless (J. Combin. Theory. A, 62, 183--215, 1993, who considered the special case $p^2$. This is achieved by explicitly giving the permutations by which two cyclic codes of prime power length are equivalent. This allows us to obtain an algorithm which solves the problem of equivalency for cyclic codes of length $p^r$ in polynomial time. Further, we characterize the set by which two quasi-cyclic codes of length $p^rl$ can be equivalent, and prove that the affine group is one of its subsets.

Culicoides antigen extract stimulates equine blood mononuclear (BMN) cell proliferation and the release of eosinophil adherence-inducing factor(s).

Science.gov (United States)

Mckelvie, J; Foster, A P; Hamblin, A S; Cunningham, F M

2001-04-01

Intradermal injection of a Culicoides antigen extract (CAgX) induces T lymphocyte and eosinophil accumulation in the skin of horses with sweet itch. Blood mononuclear (BMN) cells from normal ponies proliferate when stimulated by mitogen (phytohaemagglutinin, PHA) or antigen (tetanus toxoid, TT) and, as shown here, release soluble factor(s) that induce eosinophil adherence. CAgX also caused concentration dependent proliferation of BMN cells from sweet itch and normal ponies [stimulation index: 29 (13) and 17 (7) for BMN cells from sweet itch and normal ponies, respectively during the active phase of disease; 4 microg protein ml(-1)CAgX; 168 h]. A heat labile factor(s) which caused eosinophil adherence was also released [sweet itch ponies: 6.0 (1.6) per cent adherence versus 1.3 (0.4) per cent; normal ponies: 6.6 (0.5) per cent adherence versus 0.9 (0.1) per cent for supernatants from CAgX (4 microg protein ml(-1); 48 hours) stimulated versus unstimulated BMN cells, respectively]. These results suggest that soluble proteins released from T lymphocytes could affect eosinophil function in the lesional skin of sweet itch horses. Copyright 2001 Harcourt Publishers Ltd.

Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.

Science.gov (United States)

Doyle, Michael L; Tian, Shin-Shay; Miller, Stephen G; Kessler, Linda; Baker, Audrey E; Brigham-Burke, Michael R; Dillon, Susan B; Duffy, Kevin J; Keenan, Richard M; Lehr, Ruth; Rosen, Jon; Schneeweis, Lumelle A; Trill, John; Young, Peter R; Luengo, Juan I; Lamb, Peter

2003-03-14

Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte colony-stimulating factor receptor, expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte colony-stimulating factor are used clinically to treat neutropenias. As part of an effort to develop granulocyte colony-stimulating factor mimics with the potential for oral bioavailability, we previously identified a nonpeptidyl small molecule (SB-247464) that selectively activates murine granulocyte colony-stimulating factor signal transduction pathways and promotes neutrophil formation in vivo. To elucidate the mechanism of action of SB-247464, a series of cell-based and biochemical assays were performed. The activity of SB-247464 is strictly dependent on the presence of zinc ions. Titration microcalorimetry experiments using a soluble murine granulocyte colony-stimulating factor receptor construct show that SB-247464 binds to the extracellular domain of the receptor in a zinc ion-dependent manner. Analytical ultracentrifugation studies demonstrate that SB-247464 induces self-association of the N-terminal three-domain fragment in a manner that is consistent with dimerization. SB-247464 induces internalization of granulocyte colony-stimulating factor receptor on intact cells, consistent with a mechanism involving receptor oligomerization. These data show that small nonpeptidyl compounds are capable of selectively binding and inducing productive oligomerization of cytokine receptors.

Fluorine-18 fluorodeoxyglucose splenic uptake from extramedullary hematopoiesis after granulocyte colony-stimulating factor stimulation.

Science.gov (United States)

Abdel-Dayem, H M; Rosen, G; El-Zeftawy, H; Naddaf, S; Kumar, M; Atay, S; Cacavio, A

1999-05-01

Two patients with sarcoma, one with recurrent osteosarcoma of the spine and the other with metastatic synovial cell sarcoma, were treated with high-dose chemotherapy that produced severe leukopenia. The patients received granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow (480 mg given subcutaneously twice daily for 5 to 7 days); their responses were seen as a marked increase in peripheral leukocyte count with no change in the erythrocyte or platelet counts. The patients had fluorine-18 fluorodeoxyglucose (F-18 FDG) imaging 24 hours after the end of G-CSF treatment. Diffusely increased uptake of F-18 FDG was seen in the bone marrow in both patients. In addition, markedly increased uptake in the spleen was noted in both, indicating that the spleen was the site of extramedullary hematopoiesis. The patients had no evidence of splenic metastases. The first patient had a history of irradiation to the dorsal spine, which was less responsive to G-CSF administration than was the nonirradiated lumbar spine.

Phenotype overlap in Xylella fastidiosa is controlled by the cyclic di-GMP phosphodiesterase Eal in response to antibiotic exposure and diffusible signal factor-mediated cell-cell signaling.

Science.gov (United States)

de Souza, Alessandra A; Ionescu, Michael; Baccari, Clelia; da Silva, Aline M; Lindow, Steven E

2013-06-01

Eal is an EAL domain protein in Xylella fastidiosa homologous to one involved in resistance to tobramycin in Pseudomonas aeruginosa. EAL and HD-GYP domain proteins are implicated in the hydrolysis of the secondary messenger bis-(3'-5')-cyclic dimeric GMP (cyclic di-GMP). Cell density-dependent communication mediated by a Diffusible Signal Factor (DSF) also modulates cyclic di-GMP levels in X. fastidiosa, thereby controlling the expression of virulence genes and genes involved in insect transmission. The possible linkage of Eal to both extrinsic factors such as antibiotics and intrinsic factors such as quorum sensing, and whether both affect virulence, was thus addressed. Expression of eal was induced by subinhibitory concentrations of tobramycin, and an eal deletion mutant was more susceptible to this antibiotic than the wild-type strain and exhibited phenotypes similar to those of an rpfF deletion mutant blocked in DSF production, such as hypermotility, reduced biofilm formation, and hypervirulence to grape. Consistent with that, the rpfF mutant was more susceptible than the wild-type strain to tobramycin. Therefore, we propose that cell-cell communication and antibiotic stress can apparently lead to similar modulations of cyclic di-GMP in X. fastidiosa, resulting in similar phenotypes. However, the effect of cell density is dominant compared to that of antibiotic stress, since eal is suppressed by RpfF, which may prevent inappropriate behavioral changes in response to antibiotic stress when DSF accumulates.

Macrophage colony-stimulating factor, CSF-1, and its proto-oncogene-encoded receptor

International Nuclear Information System (INIS)

Sherr, C.J.; Rettenmier, C.W.; Roussel, M.F.

1988-01-01

The macrophage colony-stimulating factor, CSF-1, or M-CSF, is one of a family of hematopoietic growth factors that stimulates the proliferation of monocytes, macrophages, and their committed bone marrow progenitors. Unlike pluripotent hemopoietins such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3 or multi-CSF), which affect the growth of myeloid cells of several different hematopoietic lineages, CSF-1 acts only on cells of the mononuclear phagocyte series to stimulate their growth and enhance their survival. Retroviral transduction of the feline c-fms gene in the Susan McDonough and Hardy Zuckerman-5 (HZ-5) strains of feline sarcoma virus (FeSV) led to genetic alterations that endowed the recombined viral oncogene (v-fms) with the ability to transform cells in culture morphologically and to induce firbrosarcomas and hematopoietic neoplasms in susceptible animals. The v-fms oncogene product differs from the normal CSF-1 receptor in certain of its cardinal biochemical properties, most notably in exhibiting constitutively high basal levels of tyrosine kinase activity in the absence of its ligand. Comparative studies of the c-fms and v-fms genes coupled with analyses of engineered mutants and receptor chimeras have begun to pinpoint pertinent genetic alterations in the normal receptor gene that unmask its latent oncogenic potential. In addition, the availability of biologically active c-fms, v-fms, and CSF-1 cDNAs has allowed these genes to be mobilized and expressed in naive cells, thereby facilitating assays for receptor coupling with downstream components of the mitogenic pathway in diverse cell types

Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

Directory of Open Access Journals (Sweden)

Kirtan Nautiyal

2015-01-01

Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

Compressed sensing with cyclic-S Hadamard matrix for terahertz imaging applications

Science.gov (United States)

Ermeydan, Esra Şengün; ćankaya, Ilyas

2018-01-01

Compressed Sensing (CS) with Cyclic-S Hadamard matrix is proposed for single pixel imaging applications in this study. In single pixel imaging scheme, N = r . c samples should be taken for r×c pixel image where . denotes multiplication. CS is a popular technique claiming that the sparse signals can be reconstructed with samples under Nyquist rate. Therefore to solve the slow data acquisition problem in Terahertz (THz) single pixel imaging, CS is a good candidate. However, changing mask for each measurement is a challenging problem since there is no commercial Spatial Light Modulators (SLM) for THz band yet, therefore circular masks are suggested so that for each measurement one or two column shifting will be enough to change the mask. The CS masks are designed using cyclic-S matrices based on Hadamard transform for 9 × 7 and 15 × 17 pixel images within the framework of this study. The %50 compressed images are reconstructed using total variation based TVAL3 algorithm. Matlab simulations demonstrates that cyclic-S matrices can be used for single pixel imaging based on CS. The circular masks have the advantage to reduce the mechanical SLMs to a single sliding strip, whereas the CS helps to reduce acquisition time and energy since it allows to reconstruct the image from fewer samples.

Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

International Nuclear Information System (INIS)

Ahren, B.

1987-01-01

It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with 125 I and thyroxine; the subsequent release of 125 I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse

Monitoring of Cyclic Steam Stimulation by Inversion of Surface Tilt Measurements

Science.gov (United States)

Maharramov, M.; Zoback, M. D.

2014-12-01

Temperature and pressure changes associated with the cyclic steam simulation (CSS) used in heavy oil production from sands are accompanied by significant deformation. Inversion of geomechanical data may provide a potentially powerful reservoir monitoring tool where geomechanical effects are significant. Induced pore pressure changes can be inverted from measurable surface deformations by solving an inverse problem of poroelasticity. In this work, we apply this approach to estimating pore pressure changes from surface tilt measurements at a heavy oil reservoir undergoing cyclic steam simulation. Steam was injected from November 2007 through January 2008. Surface tilt measurements were collected from 25 surface tilt stations during this period. The injection ran in two overlapping phases: Phase 1 ran from the beginning of the injection though mid-December, and Phase 2 overlapped with Phase 1 and ran through the beginning of January. During Phase 1 steam was injected in the western part of the reservoir, followed by injection in the eastern part in Phase 2. The pore pressure evolution was inverted from daily tilt measurements using regularized constrained least squares fitting, the results are shown on the plot. Estimated induced pore pressure change (color scale), observed daily incremental tilts (green arrows) and modeled daily incremental tilts (red arrows) are shown in three panels corresponding to two and five weeks of injection, and the end of injection period. DGPS measurements available for a single location were used as an additional inversion constraint. The results indicate that the pore pressure increase in the reservoir follows the same pattern as the steam injection, from west to east. This qualitative behaviour is independent of the amount of regularization, indirectly validating our inversion approach. Patches of lower pressure appear to be stable with regard to regularization and may provide valuable insight into the efficiency of steam injection

Characterisation of chloride transport and reinforcement corrosion in concrete under cyclic wetting and drying by electrical resistivity

NARCIS (Netherlands)

Polder, R.B.; Peelen, W.H.A.

2002-01-01

Concrete prisms were made with four cement types including cements with fly ash and/or blast furnace slag and three waterto- cement (w/c) ratios. Chloride penetration and corrosion of rebars were stimulated by subjecting prisms to cyclic loading with salt solution and drying. Concrete resistivity,

BCYCLIC: A parallel block tridiagonal matrix cyclic solver

Science.gov (United States)

Hirshman, S. P.; Perumalla, K. S.; Lynch, V. E.; Sanchez, R.

2010-09-01

A block tridiagonal matrix is factored with minimal fill-in using a cyclic reduction algorithm that is easily parallelized. Storage of the factored blocks allows the application of the inverse to multiple right-hand sides which may not be known at factorization time. Scalability with the number of block rows is achieved with cyclic reduction, while scalability with the block size is achieved using multithreaded routines (OpenMP, GotoBLAS) for block matrix manipulation. This dual scalability is a noteworthy feature of this new solver, as well as its ability to efficiently handle arbitrary (non-powers-of-2) block row and processor numbers. Comparison with a state-of-the art parallel sparse solver is presented. It is expected that this new solver will allow many physical applications to optimally use the parallel resources on current supercomputers. Example usage of the solver in magneto-hydrodynamic (MHD), three-dimensional equilibrium solvers for high-temperature fusion plasmas is cited.

Finite-Element Modeling of Viscoelastic Cells During High-Frequency Cyclic Strain

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David W. Holdsworth

2012-03-01

Full Text Available Mechanotransduction refers to the mechanisms by which cells sense and respond to local loads and forces. The process of mechanotransduction plays an important role both in maintaining tissue viability and in remodeling to repair damage; moreover, it may be involved in the initiation and progression of diseases such as osteoarthritis and osteoporosis. An understanding of the mechanisms by which cells respond to surrounding tissue matrices or artificial biomaterials is crucial in regenerative medicine and in influencing cellular differentiation. Recent studies have shown that some cells may be most sensitive to low-amplitude, high-frequency (i.e., 1–100 Hz mechanical stimulation. Advances in finite-element modeling have made it possible to simulate high-frequency mechanical loading of cells. We have developed a viscoelastic finite-element model of an osteoblastic cell (including cytoskeletal actin stress fibers, attached to an elastomeric membrane undergoing cyclic isotropic radial strain with a peak value of 1,000 µstrain. The results indicate that cells experience significant stress and strain amplification when undergoing high-frequency strain, with peak values of cytoplasmic strain five times higher at 45 Hz than at 1 Hz, and peak Von Mises stress in the nucleus increased by a factor of two. Focal stress and strain amplification in cells undergoing high-frequency mechanical stimulation may play an important role in mechanotransduction.

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

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Nahyun Choi

2018-02-01

Full Text Available Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs. We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif ligand 1 (CXCL1, platelet-derived endothelial cell growth factor (PD-ECGF, and platelet-derived growth factor-C (PDGF-C. Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2 phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

Science.gov (United States)

Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

2018-01-01

Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box.

Science.gov (United States)

Kageyama, R; Merlino, G T; Pastan, I

1989-09-15

Transcription factor ETF stimulates the expression of the epidermal growth factor receptor (EGFR) gene which does not have a TATA box in the promoter region. Here, we show that ETF recognizes various GC-rich sequences including stretches of deoxycytidine or deoxyguanosine residues and GC boxes with similar affinities. ETF also binds to TATA boxes but with a lower affinity. ETF stimulated in vitro transcription from several promoters without TATA boxes but had little or no effect on TATA box-containing promoters even though they had strong ETF-binding sites. These inactive ETF-binding sites became functional when placed upstream of the EGFR promoter whose own ETF-binding sites were removed. Furthermore, when a TATA box was introduced into the EGFR promoter, the responsiveness to ETF was abolished. These results indicate that ETF is a specific transcription factor for promoters which do not contain TATA elements.

Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

Science.gov (United States)

Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

2016-01-01

Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

Z₂-double cyclic codes

OpenAIRE

Borges, J.

2014-01-01

A binary linear code C is a Z2-double cyclic code if the set of coordinates can be partitioned into two subsets such that any cyclic shift of the coordinates of both subsets leaves invariant the code. These codes can be identified as submodules of the Z2[x]-module Z2[x]/(x^r − 1) × Z2[x]/(x^s − 1). We determine the structure of Z2-double cyclic codes giving the generator polynomials of these codes. The related polynomial representation of Z2-double cyclic codes and its duals, and the relation...

Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activation

International Nuclear Information System (INIS)

Blanc-Brude, Olivier P.; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

2005-01-01

Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR 1 ). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR 1 -deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR 1 -specific agonists and inhibitors were used to demonstrate that PAR 1 mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR 1 and not PAR 2 . These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis

Performance study of K{sub e} factors in simplified elastic plastic fatigue analyses with emphasis on thermal cyclic loading

Energy Technology Data Exchange (ETDEWEB)

Lang, Hermann, E-mail: hermann.lang@areva.com [AREVA NP GmbH, PEEA-G, Henri-Dunant-Strasse 50, 91058 Erlangen (Germany); Rudolph, Juergen; Ziegler, Rainer [AREVA NP GmbH, PEEA-G, Henri-Dunant-Strasse 50, 91058 Erlangen (Germany)

2011-08-15

As code-based fully elastic plastic code conforming fatigue analyses are still time consuming, simplified elastic plastic analysis is often applied. This procedure is known to be overly conservative for some conditions due to the applied plastification (penalty) factor K{sub e}. As a consequence, less conservative fully elastic plastic fatigue analyses based on non-linear finite element analyses (FEA) or simplified elastic plastic analysis based on more realistic K{sub e} factors have to be used for fatigue design. The demand for more realistic K{sub e} factors is covered as a requirement of practical fatigue analysis. Different code-based K{sub e} procedures are reviewed in this paper with special regard to performance under thermal cyclic loading conditions. Other approximation formulae such as those by Neuber, Seeger/Beste or Kuehnapfel are not evaluated in this context because of their applicability to mechanical loading excluding thermal cyclic loading conditions typical for power plant operation. Besides the current code-based K{sub e} corrections, the ASME Code Case N-779 (e.g. Adam's proposal) and its modification in ASME Section VIII is considered. Comparison of elastic plastic results and results from the Rules for Nuclear Facility Components and Rules for Pressure Vessels reveals a considerable overestimation of usage factor in the case of ASME III and KTA 3201.2 for the examined examples. Usage factors according to RCC-M, Adams (ASME Code Case N-779), ASME VIII (alternative) and EN 13445-3 are essentially comparable and less conservative for these examples. The K{sub v} correction as well as the applied yield criterion (Tresca or von Mises) essentially influence the quality of the more advanced plasticity corrections (e.g. ASME Code Case N-779 and RCC-M). Hence, new proposals are based on a refined K{sub v} correction.

Study on elastic-plastic deformation analysis using a cyclic stress-strain curve

International Nuclear Information System (INIS)

Igari, Toshihide; Setoguchi, Katsuya; Yamauchi, Masafumi

1983-01-01

This paper presents the results of the elastic-plastic deformation analysis using a cyclic stress-strain curve with an intention to apply this method for predicting the low-cycle fatigue life. Uniaxial plastic cycling tests were performed on 2 1/4Cr-1Mo steel to investigate the correspondence between the cyclic stress-strain curve and the hysteresis loop, and also to determine what mathematical model should be used for analysis of deformation at stress reversal. Furthermore, a cyclic in-plane bending test was performed on a flat plate to clarify the validity of the cyclic stress-strain curve-based theoretical analysis. The results obtained are as follows: (1) The cyclic stress-strain curve corresponds nearly to the ascending curve of hysteresis loop scaled by a factor of 1/2 for both stress and strain. Therefore, the cyclic stress-strain curve can be determined from the shape of hysteresis loop, for simplicity. (2) To perform the elastic-plastic deformation analysis using the cyclic stress-strain curve is both practical and effective for predicting the cyclic elastic-plastic deformation of structures at the stage of advanced cycles. And Masing model can serve as a suitable mathematical model for such a deformation analysis. (author)

Cyclic Nucleotide Signalling in Kidney Fibrosis

Directory of Open Access Journals (Sweden)

Elisabeth Schinner

2015-01-01

Full Text Available Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure.

A conjugate of decyltriphenylphosphonium with plastoquinone can carry cyclic adenosine monophosphate, but not cyclic guanosine monophosphate, across artificial and natural membranes.

Science.gov (United States)

Firsov, Alexander M; Rybalkina, Irina G; Kotova, Elena A; Rokitskaya, Tatyana I; Tashlitsky, Vadim N; Korshunova, Galina A; Rybalkin, Sergei D; Antonenko, Yuri N

2018-02-01

The present study demonstrated for the first time the interaction between adenosine 3',5'-cyclic monophosphate (cAMP), one of the most important signaling compounds in living organisms, and the mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1). The data obtained on model liquid membranes and human platelets revealed the ability of SkQ1 to selectively transport cAMP, but not guanosine 3',5'-cyclic monophosphate (cGMP), across both artificial and natural membranes. In particular, SkQ1 elicited translocation of cAMP from the source to the receiving phase of a Pressman-type cell, while showing low activity with cGMP. Importantly, only conjugate with plastoquinone, but not dodecyl-triphenylphosphonium, was effective in carrying cAMP. In human platelets, SkQ1 also appeared to serve as a carrier of cAMP, but not cGMP, from outside to inside the cell, as measured by phosphorylation of the vasodilator stimulated phosphoprotein. The SkQ1-induced transfer of cAMP across the plasma membrane found here can be tentatively suggested to interfere with cAMP signaling pathways in living cells. Copyright © 2017 Elsevier B.V. All rights reserved.

The opposing effects of calmodulin, adenosine 5 prime -triphosphate, and pertussis toxin on phorbol ester induced inhibition of atrial natriuretic factor stimulated guanylate cyclase in SK-NEP-1 cells

Energy Technology Data Exchange (ETDEWEB)

Sekiya, M.; Frohlich, E.D.; Cole, F.E. (Alton Ochsner Medical Foundation, New Orleans, LA (USA))

1991-01-01

In the present study, we investigated the effects of calmodulin, adenosine 5{prime}-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guanylate cyclase activity in particulate membranes by about 65%. Calmodulin reversed this inhibition in a dose dependent manner. ATP potentiated Mg++ but not Mn++ supported guanylate cyclase activity. In PMA treated membranes, ATP potentiating effects were abolished. PMA also inhibited ANF-stimulated cGMP accumulation, but pretreatment with PT prevented this PMA inhibition. PT did not affect basal or ANF-stimulated cGMP accumulation. In conclusion, these results demonstrated that PMA inhibited ANF stimulation of particulate guanylate cyclase in opposition to the activating effects of calmodulin or ATP in SK-NEP-1 cells. The protein kinase C inhibitory effects appeared to be mediated via a PT-sensitive G protein.

Cyclic Voltammograms from First Principles

DEFF Research Database (Denmark)

Karlberg, Gustav; Jaramillo, Thomas; Skulason, Egill

2007-01-01

Cyclic voltammetry is a fundamental experimental tool for characterizing electrochemical surfaces. Whereas cyclic voltammetry is widely used within the field of electrochemistry, a way to quantitatively and directly relate the cyclic voltammogram to ab initio calculations has been lacking, even f...

Effect of cyclic plastic pre-strain on low cycle fatigue life

International Nuclear Information System (INIS)

Kanno, Satoshi; Nakane, Motoki; Yorikawa, Morio; Takagi, Yoshio

2010-01-01

In order to evaluate structural integrity of nuclear components subjected large seismic load which produce locally plastic strain, low cycle fatigue life was examined using cyclic plastic pre-strained materials of austenitic steel (SUS316, SUS316L, SUS304TP: JIS (Japanese Industrial Standards)) and ferritic steel (SFVQ1A, STS480, STPT410, SFVC2B, SS400: JIS). It was not found that cyclic plastic pre-strain up to range of 16%, 2.5 times affected on low cycle fatigue life. The validity of existing procedure of fatigue life estimation based on usage factor was confirmed when large seismic load brought nuclear materials cyclic plastic strain. (author)

Recombinant granulocyte colony-stimulating factor administered enterally to neonates is not absorbed.

Science.gov (United States)

Calhoun, Darlene A; Maheshwari, Akhil; Christensen, Robert D

2003-08-01

Granulocyte colony-stimulating factor (G-CSF) is present in liquids swallowed by the fetus and neonate; specifically, amniotic fluid, colostrum, and human milk. The swallowed G-CSF has local effects on enteric cells, which express the G-CSF receptor. However, some portion of the G-CSF ingested by the fetus and neonate might be absorbed into the circulation and have systemic actions, such as stimulating neutrophil production. To assess this possibility we sought to determine if circulating G-CSF concentrations of neonates increase after enteral administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). This was a single-center, prospective, blinded, randomized, 2 x 2 crossover study, with each infant receiving 1 dose of rhG-CSF (100 microg/kg) and 1 dose of placebo. Plasma G-CSF concentrations were measured at 2 and 4 hours after administration of the test solution. No significant change in plasma G-CSF concentration was observed after the enteral administration of rhG-CSF. On this basis, we conclude that orally administered rhG-CSF is not absorbed in significant quantities, and we speculate that the G-CSF swallowed by the fetus and neonate has local but not systemic effects.

Stimulation of phosphatidylcholine breakdown and diacylglycerol production by growth factors in Swiss-3T3 cells.

Science.gov (United States)

Price, B D; Morris, J D; Hall, A

1989-01-01

The effect of a number of growth factors on phosphatidylcholine (PtdCho) turnover in Swiss-3T3 cells was studied. Phorbol 12-myristate 13-acetate (PMA), bombesin, platelet-derived growth factor (PDGF) and vasopressin rapidly stimulated PtdCho hydrolysis, diacylglycerol (DAG) production, and PtdCho synthesis. Insulin and prostaglandin F2 alpha (PGF2 alpha) stimulated PtdCho synthesis, but not its breakdown, whereas epidermal growth factor (EGF) and bradykinin were without effect. Stimulation of PtdCho hydrolysis by the above ligands resulted in increased production of phosphocholine and DAG (due to phospholipase C activity) and significant amounts of choline, suggesting activation of a phospholipase D as well. CDP-choline and glycerophosphocholine levels were unchanged. Down-regulation of protein kinase C with PMA (400 nM, 40 h) abolished the stimulation of PtdCho hydrolysis and PtdCho synthesis by PMA, bombesin, PDGF and vasopressin, but not the stimulation of PtdCho synthesis by insulin and PGF2 alpha. PtdCho hydrolysis therefore occurs predominantly by activation of protein kinase C (either by PMA or PtdIns hydrolysis) leading to elevation of DAG levels derived from non-PtdIns(4,5)P2 sources. PtdCho synthesis occurs by both a protein kinase C-dependent pathway (stimulated by PMA, PDGF, bombesin and vasopressin) and a protein kinase C-independent pathway (stimulated by insulin and PGF2 alpha). DAG production from PtdCho hydrolysis is not the primary signal to activate protein kinase C, but may contribute to long-term activation of this kinase. PMID:2690829

Equibiaxial cyclic stretch stimulates fibroblasts to rapidly remodel fibrin.

Science.gov (United States)

Balestrini, Jenna Leigh; Billiar, Kristen Lawrence

2006-01-01

Understanding the effects of the mechanical environment on wound healing is critical for developing more effective treatments to reduce scar formation and contracture. The aim of this study was to investigate the effects of dynamic mechanical stretch on cell-mediated early wound remodeling independent of matrix alignment which obscures more subtle remodeling mechanisms. Cyclic equibiaxial stretch (16% stretch at 0.2 Hz) was applied to fibroblast-populated fibrin gel in vitro wound models for eight days. Compaction, density, tensile strength, and collagen content were quantified as functional measures of remodeling. Stretched samples were approximately ten times stronger, eight-fold more dense, and eight times thinner than statically cultured samples. These changes were accompanied by a 15% increase in net collagen but no significant differences in cell number or viability. When collagen crosslinking was inhibited in stretched samples, the extensibility increased and the strength decreased. The apparent weakening was due to a reduction in compaction rather than a decrease in ability of the tissue to withstand tensile forces. Interestingly, inhibiting collagen crosslinking had no measurable effects on the statically cultured samples. These results indicate that amplified cell-mediated compaction and even a slight addition in collagen content play substantial roles in mechanically induced wound strengthening. These findings increase our understanding of how mechanical forces guide the healing response in skin, and the methods employed in this study may also prove valuable tools for investigating stretch-induced remodeling of other planar connective tissues and for creating mechanically robust engineered tissues.

Which factors obstruct or stimulate teacher educators to use ICT innovatively?

NARCIS (Netherlands)

Drent, Marjolein; Meelissen, Martina R.M.

2007-01-01

This article discusses the factors which stimulate or limit the innovative use of ICT by teacher educators in the Netherlands. Innovative use of ICT is defined as the use of ICT applications that support the educational objectives based on the needs of the current knowledge society. Explorative path

Cyclic nucleotides and radioresistnace

International Nuclear Information System (INIS)

Kulinskij, V.I.; Mikheeva, G.A.; Zel'manovich, B.M.

1982-01-01

The addition of glucose to meat-peptone broth does not change the radiosensitizing effect (RSE) of cAMP at the logarithmic phase (LP) and the radioprotective effect (RPE) at the stationary phase (SP), but sensitization, characteristic of cGMP, disappears in SP and turns into RPE in LP. Introduction of glucose into the broth for 20 min eliminates all the effects of both cyclic nucleotides in the cya + strain while cya - mutant exhibits RSE. RSE of both cyclic nucleotides is only manifested on minimal media. These data brought confirmation of the dependence of the influence of cyclic media. These data brought confirmation of the dependence of the influence of cyclic nucleotides on radioresistance upon the metabolic status of the cell [ru

An improved Armstrong-Frederick-Type Plasticity Model for Stable Cyclic Stress-Strain Responses Considering Nonproportional Hardening

Science.gov (United States)

Li, Jing; Zhang, Zhong-ping; Li, Chun-wang

2018-03-01

This paper modified an Armstrong-Frederick-type plasticity model for investigating the stable cyclic deformation behavior of metallic materials with different sensitivity to nonproportional loadings. In the modified model, the nonproportionality factor and nonproportional cyclic hardening coefficient coupled with the Jiang-Sehitoglu incremental plasticity model were used to estimate the stable stress-strain responses of the two materials (1045HR steel and 304 stainless steel) under various tension-torsion strain paths. A new equation was proposed to calculate the nonproportionality factor on the basis of the minimum normal strain range. Procedures to determine the minimum normal strain range were presented for general multiaxial loadings. Then, the modified model requires only the cyclic strain hardening exponent and cyclic strength coefficient to determine the material constants. It is convenient for predicting the stable stress-strain responses of materials in engineering application. Comparisons showed that the modified model can reflect the effect of nonproportional cyclic hardening well.

Cyclic response and early damage evolution in multiaxial cyclic loading of 316L austenitic steel

Czech Academy of Sciences Publication Activity Database

Mazánová, Veronika; Škorík, Viktor; Kruml, Tomáš; Polák, Jaroslav

2017-01-01

Roč. 100, JUL (2017), s. 466-476 ISSN 0142-1123 R&D Projects: GA MŠk LM2015069; GA MŠk(CZ) LQ1601; GA ČR(CZ) GA13-23652S; GA ČR GA15-08826S Institutional support: RVO:68081723 Keywords : 316L steel * Crack initiation * Cyclic plasticity * Damage mechanism * Multiaxial straining Subject RIV: JL - Materials Fatigue, Friction Mechanics OBOR OECD: Audio engineering, reliability analysis Impact factor: 2.899, year: 2016

Cyclic mechanical stretch enhances BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Science.gov (United States)

Song, Yang; Tang, Yinhong; Song, Jinlin; Lei, Mingxing; Liang, Panpan; Fu, Tiwei; Su, Xudong; Zhou, Pengfei; Yang, Li; Huang, Enyi

2018-04-01

The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs. Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours. Immunostaining and confocal microscope were used to detect cytoskeleton organization. Cell cycle progression was checked by flow cytometry. Alkaline phosphatase activity was measured with a Chemiluminescence Assay Kit and was quantified with a histochemical staining assay. Matrix mineralization was examined by Alizarin Red S Staining. Mechanical stretch induces cytoskeleton reorganization and inhibits cell proliferation by preventing cells entry into S phase of the cell cycle. Although mechanical stretch alone does not induce the osteogenic differentiation of C3H10T1/2 MSCs, co-stimulation with mechanical stretch and BMP9 enhances alkaline phosphatase activity. The expression of key lineage-specific regulators (e.g., osteocalcin (OCN), SRY-related HMG-box 9, and runt-related transcription factor 2) is also increased after the co-stimulation, compared to the mechanical stretch stimulation along. Furthermore, mechanical stretch augments the BMP9-mediated bone matrix mineralization of C3H10T1/2 MSCs. Our results suggest that mechanical stretch enhances BMP9-induced osteoblastic lineage specification in C3H10T1/2 MSCs.

Visual search of cyclic spatio-temporal events

Science.gov (United States)

Gautier, Jacques; Davoine, Paule-Annick; Cunty, Claire

2018-05-01

The analysis of spatio-temporal events, and especially of relationships between their different dimensions (space-time-thematic attributes), can be done with geovisualization interfaces. But few geovisualization tools integrate the cyclic dimension of spatio-temporal event series (natural events or social events). Time Coil and Time Wave diagrams represent both the linear time and the cyclic time. By introducing a cyclic temporal scale, these diagrams may highlight the cyclic characteristics of spatio-temporal events. However, the settable cyclic temporal scales are limited to usual durations like days or months. Because of that, these diagrams cannot be used to visualize cyclic events, which reappear with an unusual period, and don't allow to make a visual search of cyclic events. Also, they don't give the possibility to identify the relationships between the cyclic behavior of the events and their spatial features, and more especially to identify localised cyclic events. The lack of possibilities to represent the cyclic time, outside of the temporal diagram of multi-view geovisualization interfaces, limits the analysis of relationships between the cyclic reappearance of events and their other dimensions. In this paper, we propose a method and a geovisualization tool, based on the extension of Time Coil and Time Wave, to provide a visual search of cyclic events, by allowing to set any possible duration to the diagram's cyclic temporal scale. We also propose a symbology approach to push the representation of the cyclic time into the map, in order to improve the analysis of relationships between space and the cyclic behavior of events.

STIMULATION OF DEFENSE FACTORS FOR OYSTERS DEPLOYED TO CONTAMINATED SITES IN PENSACOLA BAY, FLORIDA

Science.gov (United States)

A positive association between chemical contaminants and defense factors has been established for eastern oysters (Crassostrea virginica) from Florida, but it is unknown whether such factors can be stimulated through short-term exposure to contaminants in the field. Hatchery oyst...

The arabidopsis cyclic nucleotide interactome

KAUST Repository

Donaldson, Lara Elizabeth

2016-05-11

Background Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms in plants since the downstream target proteins remain unknown. This is largely due to the fact that bioinformatics searches fail to identify plant homologs of protein kinases and phosphodiesterases that are the main targets of cyclic nucleotides in animals. Methods An affinity purification technique was used to identify cyclic nucleotide binding proteins in Arabidopsis thaliana. The identified proteins were subjected to a computational analysis that included a sequence, transcriptional co-expression and functional annotation analysis in order to assess their potential role in plant cyclic nucleotide signaling. Results A total of twelve cyclic nucleotide binding proteins were identified experimentally including key enzymes in the Calvin cycle and photorespiration pathway. Importantly, eight of the twelve proteins were shown to contain putative cyclic nucleotide binding domains. Moreover, the identified proteins are post-translationally modified by nitric oxide, transcriptionally co-expressed and annotated to function in hydrogen peroxide signaling and the defence response. The activity of one of these proteins, GLYGOLATE OXIDASE 1, a photorespiratory enzyme that produces hydrogen peroxide in response to Pseudomonas, was shown to be repressed by a combination of cGMP and nitric oxide treatment. Conclusions We propose that the identified proteins function together as points of cross-talk between cyclic nucleotide, nitric oxide and reactive oxygen species signaling during the defence response.

Manual for Cyclic Triaxial Test

DEFF Research Database (Denmark)

Shajarati, Amir; Sørensen, Kris Wessel; Nielsen, Søren Kjær

This manual describes the different steps that is included in the procedure for conducting a cyclic triaxial test at the geotechnical Laboratory at Aalborg University. Furthermore it contains a chapter concerning some of the background theory for the static triaxial tests. The cyclic/dynamic tria......This manual describes the different steps that is included in the procedure for conducting a cyclic triaxial test at the geotechnical Laboratory at Aalborg University. Furthermore it contains a chapter concerning some of the background theory for the static triaxial tests. The cyclic...

Cyclic cholecystokinin analogues with high selectivity for central receptors

International Nuclear Information System (INIS)

Charpentier, B.; Pelaprat, D.; Durieux, C.; Dor, A.; Roques, B.P.; Reibaud, M.; Blanchard, J.C.

1988-01-01

Taking as a model the N-terminal folding of the cholecystokinin tyrosine-sulfated octapeptide deduced from conformational studies, two cyclic cholecystokinin (CCK) analogues were synthesized by conventional peptide synthesis. The binding characteristics of these peptides were investigated on brain cortex membranes and pancreatic acini of guinea pig. Compounds I and II were competitive inhibitors of [ 3 H]Boc[Ahx 28,31 ]CCK-(27-33) binding to central CCK receptors and showed a high degree of selectivity for these binding sites. This high selectivity was associated with a high affinity for central CCK receptors. Similar affinities and selectivities were found when 125 I Bolton-Hunter-labeled CCK-8 was used as a ligand. Moreover, these compounds were only weakly active in the stimulation of amylase release from guinea pig pancreatic acini and were unable to induce contractions in the guinea pig ileum. The two cyclic CCK analogues, therefore, appear to be synthetic ligands exhibiting both high affinity and high selectivity for central CCK binding sites. These compounds could help clarify the respective role of central and peripheral receptors for various CCK-8-induced pharmacological effects

Short bursts of cyclic mechanical compression modulate tissue formation in a 3D hybrid scaffold.

Science.gov (United States)

Brunelli, M; Perrault, C M; Lacroix, D

2017-07-01

Among the cues affecting cells behaviour, mechanical stimuli are known to have a key role in tissue formation and mineralization of bone cells. While soft scaffolds are better at mimicking the extracellular environment, they cannot withstand the high loads required to be efficient substitutes for bone in vivo. We propose a 3D hybrid scaffold combining the load-bearing capabilities of polycaprolactone (PCL) and the ECM-like chemistry of collagen gel to support the dynamic mechanical differentiation of human embryonic mesodermal progenitor cells (hES-MPs). In this study, hES-MPs were cultured in vitro and a BOSE Bioreactor was employed to induce cells differentiation by mechanical stimulation. From day 6, samples were compressed by applying a 5% strain ramp followed by peak-to-peak 1% strain sinewaves at 1Hz for 15min. Three different conditions were tested: unloaded (U), loaded from day 6 to day 10 (L1) and loaded as L1 and from day 16 to day 20 (L2). Cell viability, DNA content and osteocalcin expression were tested. Samples were further stained with 1% osmium tetroxide in order to investigate tissue growth and mineral deposition by micro-computed tomography (µCT). Tissue growth involved volumes either inside or outside samples at day 21 for L1, suggesting cyclic stimulation is a trigger for delayed proliferative response of cells. Cyclic load also had a role in the mineralization process preventing mineral deposition when applied at the early stage of culture. Conversely, cyclic load during the late stage of culture on pre-compressed samples induced mineral formation. This study shows that short bursts of compression applied at different stages of culture have contrasting effects on the ability of hES-MPs to induce tissue formation and mineral deposition. The results pave the way for a new approach using mechanical stimulation in the development of engineered in vitro tissue as replacement for large bone fractures. Copyright © 2017 Elsevier Ltd. All rights

Highly Expressed Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte Colony-Stimulating Factor Receptor (G-CSFR) in Human Gastric Cancer Leads to Poor Survival.

Science.gov (United States)

Fan, Zhisong; Li, Yong; Zhao, Qun; Fan, Liqiao; Tan, Bibo; Zuo, Jing; Hua, Kelei; Ji, Qiang

2018-03-23

BACKGROUND Chemotherapy for advanced gastric cancer (GC) patients has been the mainstay of therapy for many years. Although adding anti-angiogenic drugs to chemotherapy improves patient survival slightly, identifying anti-angiogenic therapy-sensitive patients remains challenging for oncologists. Granulocyte colony-stimulating factor (G-CSF) promotes tumor growth and angiogenesis, which can be minimized with the anti-G-CSF antibody. Thus, G-CSF might be a potential tumor marker. However, the effects of G-CSF and G-CSFR expression on GC patient survival remain unclear. MATERIAL AND METHODS Seventy GC tissue samples were collected for G-CSF and G-CSFR detection by immunohistochemistry. A total of 40 paired GC tissues and matched adjacent mucosa were used to measure the G-CSF and G-CSFR levels by ELISA. Correlations between G-CSF/G-CSFR and clinical characteristics, VEGF-A levels and overall survival were analyzed. Biological function and underlying mechanistic investigations were carried out using SGC7901 cell lines, and the effects of G-CSF on tumor proliferation, migration, and tube formation were examined. RESULTS The levels of G-CSFR were upregulated in GC tissues compared to normal mucosa tissues. Higher G-CSF expression was associated with later tumor stages and higher tumor VEGF-A and serum CA724 levels, whereas higher G-CSFR expression was associated with lymph node metastasis. Patients with higher G-CSF expression had shorter overall survival times. In vitro, G-CSF stimulated SGC7901 proliferation and migration through the JAK2/STAT3 pathway and accelerated HUVEC tube formation. CONCLUSIONS These data suggest that increased G-CSF and G-CSFR in tumors leads to unfavorable outcomes for GC patients by stimulating tumor proliferation, migration, and angiogenesis, indicating that these factors are potential tumor targets for cancer treatment.

Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s)

International Nuclear Information System (INIS)

Ellsworth, J.L.; Brown, C.; Cooper, A.D.

1988-01-01

The regulation of low-density lipoprotein (LDL) receptor activity in the human hepatoma cell line Hep-G2 by serum components was examined. Incubation of dense monolayers of Hep-G2 cells with fresh medium containing 10% fetal calf serum (FM) produced a time-dependent increase in LDL receptor activity. Uptake and degradation of 125I-LDL was stimulated two- to four-fold, as compared with that of Hep-G2 cells cultured in the same media in which they had been grown to confluence (CM); the maximal 125I-LDL uptake plus degradation increased from 0.2 microgram/mg cell protein/4 h to 0.8 microgram/mg cell protein/4 h. In addition, a two-fold increase in cell surface binding of 125I-LDL to Hep-G2 cells was observed when binding was measured at 4 degrees C. There was no change in the apparent Kd. The stimulation of LDL receptor activity was suppressed in a concentration-dependent manner by the addition of cholesterol, as LDL, to the cell medium. In contrast to the stimulation of LDL receptor activity, FM did not affect the uptake or degradation of 125I-asialoorosomucoid. Addition of FM increased the protein content per dish, and DNA synthesis was stimulated approximately five-fold, as measured by [3H]thymidine incorporation into DNA; however, the cell number did not change. Cellular cholesterol biosynthesis was also stimulated by FM; [14C]acetate incorporation into unesterified and esterified cholesterol was increased approximately five-fold. Incubation of Hep-G2 cells with high-density lipoproteins (200 micrograms protein/ml) or albumin (8.0 mg/ml) in the absence of the serum factor did not significantly increase the total processed 125I-LDL. Stimulation of LDL receptor activity was dependent on a heat-stable, nondialyzable serum component that eluted in the inclusion volume of a Sephadex G-75 column

Overexpression of cyclic adenosine monophosphate effluent protein MRP4 induces an altered response to β-adrenergic stimulation in the senescent rat heart.

Science.gov (United States)

Carillion, Aude; Feldman, Sarah; Jiang, Cheng; Atassi, Fabrice; Na, Na; Mougenot, Nathalie; Besse, Sophie; Hulot, Jean-Sébastien; Riou, Bruno; Amour, Julien

2015-02-01

In the senescent heart, the positive inotropic response to β-adrenoceptor stimulation is reduced, partly by dysregulation of β1- and β3-adrenoceptors. The multidrug resistance protein 4 (MRP4) takes part in the control of intracellular cyclic adenosine monophosphate concentration by controlling its efflux but the role of MRP4 in the β-adrenergic dysfunction of the senescent heart remains unknown. The β-adrenergic responses to isoproterenol were investigated in vivo (stress echocardiography) and in vitro (isolated cardiomyocyte by Ionoptix with sarcomere shortening and calcium transient) in young (3 months old) and senescent (24 months old) rats pretreated or not with MK571, a specific MRP4 inhibitor. MRP4 was quantified in left ventricular homogenates by Western blotting. Data are mean ± SD expressed as percent of baseline value. The positive inotropic effect of isoproterenol was reduced in senescent rats in vivo (left ventricular shortening fraction 120 ± 16% vs. 158 ± 20%, P < 0.001, n = 16 rats) and in vitro (sarcomere shortening 129 ± 37% vs. 148 ± 35%, P = 0.004, n = 41 or 43 cells) as compared to young rats. MRP4 expression increased 3.6-fold in senescent compared to young rat myocardium (P = 0.012, n = 8 rats per group). In senescent rats, inhibition of MRP4 by MK571 restored the positive inotropic effect of isoproterenol in vivo (143 ± 11%, n = 8 rats). In vitro in senescent cardiomyocytes pretreated with MK571, both sarcomere shortening (161 ± 45% vs. 129 ± 37%, P = 0.007, n = 41 cells per group) and calcium transient amplitude (132 ± 25% vs. 113 ± 27%, P = 0.007) increased significantly. MRP4 overexpression contributes to the reduction of the positive inotropic response to β-adrenoceptor stimulation in the senescent heart.

Production of humoral factors that stimulate spleen colony-forming units in mice irradiated with moderate doses of X rays

International Nuclear Information System (INIS)

Grande, T.; Gonzalez, J.; Tejero, C.; Maganto, G.; Bueren, J.A.

1990-01-01

The production of humoral factors that stimulate spleen colony-forming units (CFU-S) has been studied in irradiated mice using an in vivo diffusion chamber assay. The experiments show that a significant release of factors that stimulate CFU-S takes place in the first few days after irradiation with moderate doses of 1.5 or 5 Gy. In contrast, the release of significant amounts of these humoral factors was not seen in animals irradiated with either low (0.75 Gy) or high (10 Gy) doses of X rays. The correlation observed between the production of factors that stimulate the CFU-S and the hemopoietic regeneration kinetics of the irradiated mice suggests that these factors represent part of the physiological regulators controlling the proliferation of CFU-S

Deformation mechanisms in cyclic creep and fatigue

International Nuclear Information System (INIS)

Laird, C.

1979-01-01

Service conditions in which static and cyclic loading occur in conjunction are numerous. It is argued that an understanding of cyclic creep and cyclic deformation are necessary both for design and for understanding creep-fatigue fracture. Accordingly a brief, and selective, review of cyclic creep and cyclic deformation at both low and high strain amplitudes is provided. Cyclic loading in conjunction with static loading can lead to creep retardation if cyclic hardening occurs, or creep acceleration if softening occurs. Low strain amplitude cyclic deformation is understood in terms of dislocation loop patch and persistent slip band behavior, high strain deformation in terms of dislocation cell-shuttling models. While interesting advances in these fields have been made in the last few years, the deformation mechanisms are generally poorly understood

Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition

Science.gov (United States)

Rothdiener, Miriam; Hegemann, Miriam; Uynuk-Ool, Tatiana; Walters, Brandan; Papugy, Piruntha; Nguyen, Phong; Claus, Valentin; Seeger, Tanja; Stoeckle, Ulrich; Boehme, Karen A.; Aicher, Wilhelm K.; Stegemann, Jan P.; Hart, Melanie L.; Kurz, Bodo; Klein, Gerd; Rolauffs, Bernd

2016-10-01

Using matrix elasticity and cyclic stretch have been investigated for inducing mesenchymal stromal cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage but not in combination. We hypothesized that combining lineage-specific stiffness with cyclic stretch would result in a significantly increased expression of SMC markers, compared to non-stretched controls. First, we generated dense collagen type I sheets by mechanically compressing collagen hydrogels. Atomic force microscopy revealed a nanoscale stiffness range known to support myogenic differentiation. Further characterization revealed viscoelasticity and stable biomechanical properties under cyclic stretch with >99% viable adherent human MSC. MSCs on collagen sheets demonstrated a significantly increased mRNA but not protein expression of SMC markers, compared to on culture flasks. However, cyclic stretch of MSCs on collagen sheets significantly increased both mRNA and protein expression of α-smooth muscle actin, transgelin, and calponin versus plastic and non-stretched sheets. Thus, lineage-specific stiffness and cyclic stretch can be applied together for inducing MSC differentiation towards SMCs without the addition of recombinant growth factors or other soluble factors. This represents a novel stimulation method for modulating the phenotype of MSCs towards SMCs that could easily be incorporated into currently available methodologies to obtain a more targeted control of MSC phenotype.

Granulocyte-Macrophage Colony-Stimulating Factor Amplification of Interleukin-1β and Tumor Necrosis Factor Alpha Production in THP-1 Human Monocytic Cells Stimulated with Lipopolysaccharide of Oral Microorganisms

OpenAIRE

Baqui, A. A. M. A.; Meiller, Timothy F.; Chon, Jennifer J.; Turng, Been-Foo; Falkler, William A.

1998-01-01

Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) play important roles in inflammatory processes, including exacerbation of periodontal diseases, one of the most common complications in patients who undergo this therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1β and TNF-α production following GM-CSF suppl...

Cyclic settlement behavior of strip footings resting on reinforced layered sand slope

Directory of Open Access Journals (Sweden)

Mostafa A. El Sawwaf

2012-10-01

Full Text Available The paper presents a study of the behavior of model strip footings supported on a loose sandy slope and subjected to both monotonic and cyclic loads. The effects of the partial replacement of a compacted sand layer and the inclusion of geosynthetic reinforcement were investigated. Different combinations of the initial monotonic loads and the amplitude of cyclic loads were chosen to simulate structures in which loads change cyclically such as machine foundations. The affecting factors including the location of footing relative to the slope crest, the frequency of the cyclic load and the number of load cycles were studied. The cumulative cyclic settlement of the model footing supported on a loose sandy slope, un-reinforced and reinforced replaced sand deposits overlying the loose slope were obtained and compared. Test results indicate that the inclusion of soil reinforcement in the replaced sand not only significantly increases the stability of the sandy slope itself but also decreases much both the monotonic and cumulative cyclic settlements leading to an economic design of the footings. However, the efficiency of the sand–geogrid systems depends on the properties of the cyclic load and the location of the footing relative to the slope crest. Based on the test results, the variation of cumulative settlements with different parameters is presented and discussed.

Complexity of chemical graphs in terms of size, branching, and cyclicity.

Science.gov (United States)

Balaban, A T; Mills, D; Kodali, V; Basak, S C

2006-08-01

Chemical graph complexity depends on many factors, but the main ones are size, branching, and cyclicity. Some molecular descriptors embrace together all these three parameters, which cannot then be disentangled. The topological index J (and its refinements that include accounting for bond multiplicity and the presence of heteroatoms) was designed to compensate in a significant measure for graph size and cyclicity, and therefore it contains information mainly on branching. In order to separate these factors, two new indices (F and G) related with J are proposed, which allow to group together graphs with the same size into families of constitutional formulas differing in their branching and cyclicity. A comparison with other topological indices revealed that a few other topological indices vary similarly with index G, notably DN2S4 among the triplet indices, and TOTOP among the indices contained in the Molconn-Z program. This comparison involved all possible chemical graphs (i.e. connected planar graphs with vertex degrees not higher than four) with four through six vertices, and all possible alkanes with four through nine carbon atoms.

Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

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Michal Hofer

2014-04-01

Full Text Available This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF, in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

Cyclic Vomiting Syndrome in Children

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T.V. Sorokman

2016-08-01

Full Text Available Introduction. Cyclic vomiting syndrome (CVS — is a fairly common disease of unknown etiology that affects children of all age groups and sometimes adult population and refers to the functional disorders of the gastrointestinal tract. Objective: to evaluate the effectiveness of the usage of Rehydron Optim for oral rehydration therapy in children. Materials and methods. The treatment of 40 children aged 3 to 11 years with CVS (15 persons and primary acetonemic syndrome (25 persons in the period of acetonemic crisis, including 15 boys and 25 girls, was analyzed. All children were observed in the outpatient department of the Regional children’s hospital of Chernivtsi. Diagnosis was established based on anamnesis, clinical and laboratory data. Patients underwent required clinico-biological tests and instrumental examinations. The dynamics of the following syndromes was investigated: pain, vomiting, dehydration and intoxication. Rehydration therapy in all cases was oral with the usage of Rehydron Optim. Results of the study and their discussion. A cyclical vomiting was observed in children with primary acetonemic syndrome with satisfactory condition in attack-free period. Migraine-like headaches prevailed in 36 patients (80 %, and the age of these patients was older than 7 years. Same children had episodes of paroxysmal autonomic failure. Almost all surveyed children had in their family history the risk factors for CVS development. All children had positive dynamics of the main basic clinical manifestations on the background of oral rehydration therapy using Rehydron Optim. Within the 1st day of oral rehydration therapy with Rehydron Optim in children, we have noted a significant decrease in the incidence of lethargy, vomiting, spastic abdominal pain, smell of acetone in the exhaled air (p < 0.05. In children with the I degree of dehydration, clinical signs of dehydration were not seen before the treatment, and children with the II degree had an

Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Komůrková, Denisa; Hoferová, Zuzana

2014-01-01

Roč. 19, č. 4 (2014), s. 4770-4778 ISSN 1420-3049 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : granulocyte colony-stimulating factor * radiation accident s * acute radiation syndrome Subject RIV: BO - Biophysics Impact factor: 2.416, year: 2014

Cyclic peptide therapeutics: past, present and future.

Science.gov (United States)

Zorzi, Alessandro; Deyle, Kaycie; Heinis, Christian

2017-06-01

Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics. Over 40 cyclic peptide drugs are currently in clinical use and around one new cyclic peptide drug enters the market every year on average. The vast majority of clinically approved cyclic peptides are derived from natural products, such as antimicrobials or human peptide hormones. New powerful techniques based on rational design and in vitro evolution have enabled the de novo development of cyclic peptide ligands to targets for which nature does not offer solutions. A look at the cyclic peptides currently under clinical evaluation shows that several have been developed using such techniques. This new source for cyclic peptide ligands introduces a freshness to the field, and it is likely that de novo developed cyclic peptides will be in clinical use in the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sequencing Cyclic Peptides by Multistage Mass Spectrometry

Science.gov (United States)

Mohimani, Hosein; Yang, Yu-Liang; Liu, Wei-Ting; Hsieh, Pei-Wen; Dorrestein, Pieter C.; Pevzner, Pavel A.

2012-01-01

Some of the most effective antibiotics (e.g., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of mass spectrometry based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage mass spectrometry, and show its advantages over single stage mass spectrometry. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria. PMID:21751357

STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-{alpha}2b peptide

Energy Technology Data Exchange (ETDEWEB)

Blank, Viviana C.; Pena, Clara [Institute of Biochemistry and Biophysics (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956-C1113AAD Buenos Aires (Argentina); Roguin, Leonor P., E-mail: rvroguin@qb.ffyb.uba.ar [Institute of Biochemistry and Biophysics (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956-C1113AAD Buenos Aires (Argentina)

2010-02-15

In the search of mimetic peptides of the interferon-{alpha}2b molecule (IFN-{alpha}2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-{alpha}2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-{alpha}2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.

STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-α2b peptide

International Nuclear Information System (INIS)

Blank, Viviana C.; Pena, Clara; Roguin, Leonor P.

2010-01-01

In the search of mimetic peptides of the interferon-α2b molecule (IFN-α2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-α2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-α2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.

The calculation of dissipated work, elastoplastic cyclic stress and cyclic strain in a structure

International Nuclear Information System (INIS)

Wang Xucheng; Xie Yihuan.

1986-01-01

With the development of the reactor technique, there is being an increasing interest in the calculation of elastoplastic response of a structure to its complex loading. This paper introduces a constitutive relation of a material for discribing unloading property, and uses it in an analysis of a real structure under a cyclic loading. The results, which include cyclic stress, cyclic strain and dissipated work, are meaningful in the researches of the structure behavior under complex loading and of the structural safety

SPR imaging combined with cyclic voltammetry for the detection of neural activity

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Hui Li

2014-03-01

Full Text Available Surface plasmon resonance (SPR detects changes in refractive index at a metal-dielectric interface. In this study, SPR imaging (SPRi combined with cyclic voltammetry (CV was applied to detect neural activity in isolated bullfrog sciatic nerves. The neural activities induced by chemical and electrical stimulation led to an SPR response, and the activities were recorded in real time. The activities of different parts of the sciatic nerve were recorded and compared. The results demonstrated that SPR imaging combined with CV is a powerful tool for the investigation of neural activity.

The rearrangements of naphthylnitrenes: UV/Vis and IR spectra of azirines, cyclic ketenimines, and cyclic nitrile ylides.

Science.gov (United States)

Maltsev, Alexander; Bally, Thomas; Tsao, Meng-Lin; Platz, Matthew S; Kuhn, Arvid; Vosswinkel, Michael; Wentrup, Curt

2004-01-14

Ar matrix photolysis of 1- and 2-naphthyl azides 3 and 4 at 313 nm initially affords the singlet naphthyl nitrenes, (1)()1 and (1)()2. Relaxation to the corresponding lower energy, persistent triplet nitrenes (3)()1 and (3)()2 competes with cyclization to the azirines 15 and 18, which can also be formed photochemically from the triplet nitrenes. On prolonged irradiation, the azirines can be converted to the seven-membered cyclic ketenimines 10 and 13, respectively, as described earlier by Dunkin and Thomson. However, instead of the o-quinoid ketenimines 16 and 19, which are the expected primary ring-opening products of azirines 15 and 18, respectively, we observed their novel bond-shift isomers 17 and 20, which may be formally regarded as cyclic nitrile ylides. The existence of such ylidic heterocumulenes has been predicted previously, but this work provides the first experimental observation of such species. The factors which are responsible for the special stability of the ylidic species 17 and 20 are discussed.

Survival Analysis of Factors Influencing Cyclic Fatigue of Nickel-Titanium Endodontic Instruments

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Eva Fišerová

2015-01-01

Full Text Available Objective. The aim of this study was to validate a survival analysis assessing the effect of type of rotary system, canal curvature, and instrument size on cyclic resistance. Materials and Methods. Cyclic fatigue testing was carried out in stainless steel artificial canals with radii of curvature of 3 or 5 mm and the angle of curvature of 60 degrees. All the instruments were new and 25 mm in working length, and ISO colour coding indicated the instrument size (yellow for size 20; red for size 25. Wizard Navigator instruments, Mtwo instruments, ProTaper instruments, and Revo-S instruments were passively rotated at 250 rotations per minute, and the time fracture was being recorded. Subsequently, fractographic analysis of broken tips was performed by scanning electron microscope. The data were then analysed by the Kaplan-Meier estimator of the survival function, the Cox proportional hazards model, the Wald test for regression covariates, and the Wald test for significance of regression model. Conclusion. The lifespan registered for the tested instruments was Mtwo > Wizard Navigator > Revo-S > ProTaper; 5 mm radius > 3 mm radius; and yellow > red in ISO colour coding system.

The Granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity

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Stephanie eWallner

2015-08-01

Full Text Available Granulocyte-colony stimulating factor (G-CSF is a growth factor that has originally been identified several decades ago as a hematopoietic factor required mainly for the generation of neutrophilic granulocytes, and is in clinical use for that. More recently, it has been discovered that G-CSF also plays a role in the brain as a growth factor for neurons and neural stem cells, and as a factor involved in the plasticity of the vasculature. We review and discuss these dual properties in view of the neuroregenerative potential of this growth factor.

The arabidopsis cyclic nucleotide interactome

KAUST Repository

Donaldson, Lara Elizabeth; Meier, Stuart Kurt; Gehring, Christoph A

2016-01-01

Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms

A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis.

Science.gov (United States)

Dey, Bappaditya; Dey, Ruchi Jain; Cheung, Laurene S; Pokkali, Supriya; Guo, Haidan; Lee, Jong-Hee; Bishai, William R

2015-04-01

Detection of cyclic-di-adenosine monophosphate (c-di-AMP), a bacterial second messenger, by the host cytoplasmic surveillance pathway (CSP) is known to elicit type I interferon (IFN) responses, which are crucial to antimicrobial defense. However, the mechanisms and role of c-di-AMP signaling in Mycobacterium tuberculosis virulence remain unclear. Here we show that resistance to tuberculosis requires CSP-mediated detection of c-di-AMP produced by M. tuberculosis and that levels of c-di-AMP modulate the fate of infection. We found that a di-adenylate cyclase (disA or dacA)-overexpressing M. tuberculosis strain that secretes excess c-di-AMP activates the interferon regulatory factor (IRF) pathway with enhanced levels of IFN-β, elicits increased macrophage autophagy, and exhibits substantial virulence attenuation in mice. We show that c-di-AMP-mediated IFN-β induction during M. tuberculosis infection requires stimulator of interferon genes (STING)-signaling. We observed that c-di-AMP induction of IFN-β is independent of the cytosolic nucleic acid receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), but cGAS nevertheless contributes substantially to the overall IFN-β response to M. tuberculosis infection. In sum, our results reveal c-di-AMP to be a key mycobacterial pathogen-associated molecular pattern (PAMP) driving host type I IFN responses and autophagy. These findings suggest that modulating the levels of this small molecule may lead to novel immunotherapeutic strategies against tuberculosis.

Granulocyte colony-stimulating factor and leukemogenesis

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Lorena Lobo de Figueiredo

2004-01-01

Full Text Available THE granulocyte colony-stimulating factor (G-CSF plays an important role in normal granulopoiesis. Its functions are mediated by specific receptors on the surface of responsive cells and, upon ligand binding, several cytoplasmic tyrosine kinases are activated. The cytoplasmic region proximal to the membrane of the G-CSF receptor (G-CSF-R transduces proliferative and survival signals, whereas the distal carboxy-terminal region transduces maturation signals and suppresses the receptor's proliferative signals. Mutations in the G-CSF-R gene resulting in truncation of the carboxy-terminal region have been detected in a subset of patients with severe congenital neutropenia who developed acute myelogenous leukemia (AML. In addition, the AML1-ETO fusion protein, expressed in leukemic cells harboring the t(8;21, disrupt the physiological function of transcription factors such as C/EBPα and C/EBPε, which in turn deregulate G-CSF-R expression. The resulting high levels of G-CSF-R and G-CSF-dependent cell proliferation may be associated with pathogenesis of AML with t(8;21. Moreover, in vitro and in vivo studies demonstrated that G-CSF may act as a co-stimulus augmenting the response of PML-RARα acute promyelocytic leukemia cells to all-trans-retinoic acid treatment. Finally, in the PLZF-RARα acute promyelocytic leukemia transgenic model, G-CSF deficiency suppressed leukemia development. Altogether, these data suggest that the G-CSF signaling pathway may play a role in leukemogenesis.

Testing and modeling of cyclically loaded rock anchors

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Joar Tistel

2017-12-01

Full Text Available The Norwegian Public Roads Administration (NPRA is planning for an upgrade of the E39 highway route at the westcoast of Norway. Fixed links shall replace ferries at seven fjord crossings. Wide spans and large depths at the crossings combined with challenging subsea topography and environmental loads call for an extension of existing practice. A variety of bridge concepts are evaluated in the feasibility study. The structures will experience significant loads from deadweight, traffic and environment. Anchoring of these forces is thus one of the challenges met in the project. Large-size subsea rock anchors are considered a viable alternative. These can be used for anchoring of floating structures but also with the purpose of increasing capacity of fixed structures. This paper presents first a thorough study of factors affecting rock anchor bond capacity. Laboratory testing of rock anchors subjected to cyclic loading is thereafter presented. Finally, the paper presents a model predicting the capacity of a rock anchor segment, in terms of a ribbed bar, subjected to a cyclic load history. The research assumes a failure mode occurring in the interface between the rock anchor and the surrounding grout. The constitutive behavior of the bonding interface is investigated for anchors subjected to cyclic one-way tensile loads. The model utilizes the static bond capacity curve as a basis, defining the ultimate bond τbu and the slip s1 at τbu. A limited number of input parameters are required to apply the model. The model defines the bond-slip behavior with the belonging rock anchor capacity depending on the cyclic load level (τmax cy/τbu, the cyclic load ratio (R = τmin cy/τmax cy, and the number of load cycles (N. The constitutive model is intended to model short anchor lengths representing an incremental length of a complete rock anchor.

40 CFR 721.2120 - Cyclic amide.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Cyclic amide. 721.2120 Section 721... Cyclic amide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as a cyclic amide (PMN P-92-131) is subject to reporting under this section for the...

Cyclic completion of the anamorphic universe

Science.gov (United States)

Ijjas, Anna

2018-04-01

Cyclic models of the universe have the advantage of avoiding initial conditions problems related to postulating any sort of beginning in time. To date, the best known viable examples of cyclic models have been ekpyrotic. In this paper, we show that the recently proposed anamorphic scenario can also be made cyclic. The key to the cyclic completion is a classically stable, non-singular bounce. Remarkably, even though the bounce construction was originally developed to connect a period of contraction with a period of expansion both described by Einstein gravity, we show here that it can naturally be modified to connect an ordinary contracting phase described by Einstein gravity with a phase of anamorphic smoothing. The paper will present the basic principles and steps in constructing cyclic anamorphic models.

Adenosine 3':5'-cyclic monophosphate in higher plants: Isolation and characterization of adenosine 3':5'-cyclic monophosphate from Kalanchoe and Agave.

Science.gov (United States)

Ashton, A R; Polya, G M

1977-01-01

1.3':5'-Cyclic AMP was extensively purified from Kalanchoe daigremontiana and Agave americana by neutral alumina and anion- and cation-exchange column chromatography. Inclusion of 3':5'-cyclic [8-3H]AMP from the point of tissue extraction permitted calculation of yields. The purification procedure removed contaminating material that was shown to interfere with the 3':5'-cyclic AMP estimation and characterization procedures. 2. The partially purified 3':5'-cyclic AMP was quantified by means of a radiochemical saturation assay using an ox heart 3':5'-cyclic AMP-binding protein and by an assay involving activation of a mammalian protein kinase. 3. The plant 3':5'-cyclic AMP co-migrated with 3':5'-cyclic [8-3H]AMP on cellulose chromatography, poly(ethyleneimine)-cellulose chromatography and silica-gel t.l.c. developed with several solvent systems. 4. The plant 3':5'-cyclic AMP was degraded by ox heart 3':5'-cyclic nucleotide phosphodiesterase at the same rates as authentic 3':5'-cyclic AMP. 1-Methyl-3-isobutylxanthine (1 mM), a specific inhibitor of the 3':5'-cyclic nucleotide phosphodieterase, completely inhibited such degradation. 5. The concentrations of 3':5'-cyclic AMP satisfying the above criteria in Kalanchoe and Agave were 2-6 and 1 pmol/g fresh wt. respectively. Possible bacterial contribution to these analyses was estimated to be less than 0.002pmol/g fresh wt. Evidence for the occurrence of 3':5'-cyclic AMP in plants is discussed. PMID:196595

Effect of cyclic pre-strain on low cycle fatigue life at middle high temperature

International Nuclear Information System (INIS)

Nakane, Motoki; Kanno, Satoshi; Takagi, Yoshio

2011-01-01

This study examined the effect of cyclic plastic pre-strain on low cycle fatigue life at middle high temperature to evaluate the structural integrity of the nuclear components introduced plastic strain to the local portion by the large seismic load. The materials selected in this study were austenitic steel (SUS316NG) and ferritic steel (SFVQ1A, STS410: JIS (Japanese Industrial Standards). The low cycle fatigue tests at RT and middle high temperature (300 degrees C) were carried out using cyclic plastic pre-strained materials. The results obtained here show that the damage by the cyclic plastic pre-strain, which is equivalent to usage factor UF=0.2, does not affect the fatigue lives of the materials. In addition, it is confirmed that the estimation based on the usage factor UF can also be useful for the life prediction at 300 degrees C as well as RT. (author)

History-independent cyclic response of nanotwinned metals

Science.gov (United States)

Pan, Qingsong; Zhou, Haofei; Lu, Qiuhong; Gao, Huajian; Lu, Lei

2017-11-01

Nearly 90 per cent of service failures of metallic components and structures are caused by fatigue at cyclic stress amplitudes much lower than the tensile strength of the materials involved. Metals typically suffer from large amounts of cumulative, irreversible damage to microstructure during cyclic deformation, leading to cyclic responses that are unstable (hardening or softening) and history-dependent. Existing rules for fatigue life prediction, such as the linear cumulative damage rule, cannot account for the effect of loading history, and engineering components are often loaded by complex cyclic stresses with variable amplitudes, mean values and frequencies, such as aircraft wings in turbulent air. It is therefore usually extremely challenging to predict cyclic behaviour and fatigue life under a realistic load spectrum. Here, through both atomistic simulations and variable-strain-amplitude cyclic loading experiments at stress amplitudes lower than the tensile strength of the metal, we report a history-independent and stable cyclic response in bulk copper samples that contain highly oriented nanoscale twins. We demonstrate that this unusual cyclic behaviour is governed by a type of correlated ‘necklace’ dislocation consisting of multiple short component dislocations in adjacent twins, connected like the links of a necklace. Such dislocations are formed in the highly oriented nanotwinned structure under cyclic loading and help to maintain the stability of twin boundaries and the reversible damage, provided that the nanotwins are tilted within about 15 degrees of the loading axis. This cyclic deformation mechanism is distinct from the conventional strain localizing mechanisms associated with irreversible microstructural damage in single-crystal, coarse-grained, ultrafine-grained and nanograined metals.

Cyclical subnormal separation in A-groups

International Nuclear Information System (INIS)

Makarfi, M.U.

1995-12-01

Three main results, concerning A-groups in respect of cyclical subnormal separation as defined in, are presented. It is shown in theorem A that any A-group that is generated by elements of prime order and satisfying the cyclical subnormal separation conditions is metabelian. The two other main results give necessary and sufficient conditions for A-groups, that are split extensions of certain abelian p-groups by a metabelian p'-group, to satisfy the cyclical subnormal separation condition. There is also a result which shows that A-groups with elementary abelian Sylow subgroups are cyclically separated as defined. (author). 7 refs

Damage assessment of low-cycle fatigue by crack growth prediction. Fatigue life under cyclic thermal stress

International Nuclear Information System (INIS)

Kamaya, Masayuki

2013-01-01

The number of cycles to failure of specimens in fatigue tests can be estimated by predicting crack growth. Under a cyclic thermal stress caused by fluctuation of fluid temperature, due to the stress gradient in the thickness direction, the estimated fatigue life differs from that estimated for mechanical fatigue tests. In this paper, the influence of crack growth under cyclic thermal loading on the fatigue life was investigated. First, the thermal stress was derived by superposing analytical solutions, and then, the stress intensity factor was obtained by the weight function method. It was shown that the thermal stress depended not on the rate of the fluid temperature change but on the rise time, and the magnitude of the stress was increased as the rise time was decreased. The stress intensity factor under the cyclic thermal stress was smaller than that under the uniform stress distribution. The change in the stress intensity factor with the crack depth was almost the same regardless of the rise time. The estimated fatigue life under the cyclic thermal loading could be 1.6 times longer than that under the uniform stress distribution. The critical size for the fatigue life determination was assumed to be 3 mm for fatigue test specimens of 10 mm diameter. By evaluating the critical size by structural integrity analyses, the fatigue life was increased and the effect of the critical size on the fatigue life was more pronounced for the cyclic thermal stress. (author)

FACTORS THAT STIMULATE THE ECOSYSTEM ROMANIAN ENTREPRENEURIAL

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ENEA CONSTANŢA

2017-12-01

Full Text Available Entrepreneurship has begun to grapple with the global economic and financial crisis, and entrepreneurs have become "heroes" capable of delivering impetus to fragile economies. Small and innovative companies account for 99% of all Europe's active companies and offer 66% of available jobs. In the context of a worrying unemployment rate that persists in many countries of the world, entrepreneurship has become a viable solution to economic problems. Entrepreneurship can not be defined precisely, and the multidimensionality and homogeneity of the concept makes it very difficult to generalize the conclusions of studies for regions other than those for which they were originally developed. The objective of the present study is to carry out a comprehensive analysis of the Romanian entrepreneurial ecosystem and the factors that have the power to stimulate it, thus allowing the design of efficient policies for the development of Romanian entrepreneurship.

Cyclic characteristics of earthquake time histories

International Nuclear Information System (INIS)

Hall, J.R. Jr; Shukla, D.K.; Kissenpfennig, J.F.

1977-01-01

From an engineering standpoint, an earthquake record may be characterized by a number of parameters, one of which is its 'cyclic characteristics'. The cyclic characteristics are most significant in fatigue analysis of structures and liquefaction analysis of soils where, in addition to the peak motion, cyclic buildup is significant. Whereas duration peak amplitude and response spectra for earthquakes have been studied extensively, the cyclic characteristics of earthquake records have not received an equivalent attention. Present procedures to define the cyclic characteristics are generally based upon counting the number of peaks at various amplitude ranges on a record. This paper presents a computer approach which describes a time history by an amplitude envelope and a phase curve. Using Fast Fourier Transform Techniques, an earthquake time history is represented as a projection along the x-axis of a rotating vector-the length the vector is given by the amplitude spectra-and the angle between the vector and x-axis is given by the phase curve. Thus one cycle is completed when the vector makes a full rotation. Based upon Miner's cumulative damage concept, the computer code automatically combines the cycles of various amplitudes to obtain the equivalent number of cycles of a given amplitude. To illustrate the overall results, the cyclic characteristics of several real and synthetic earthquake time histories have been studied and are presented in the paper, with the conclusion that this procedure provides a physical interpretation of the cyclic characteristics of earthquakes. (Auth.)

Windows(Registered Trademark)-Based Software Models Cyclic Oxidation Behavior

Science.gov (United States)

Smialek, J. L.; Auping, J. V.

2004-01-01

Oxidation of high-temperature aerospace materials is a universal issue for combustion-path components in turbine or rocket engines. In addition to the question of the consumption of material due to growth of protective scale at use temperatures, there is also the question of cyclic effects and spallation of scale on cooldown. The spallation results in the removal of part of the protective oxide in a discontinuous step and thereby opens the way for more rapid oxidation upon reheating. In experiments, cyclic oxidation behavior is most commonly characterized by measuring changes in weight during extended time intervals that include hundreds or thousands of heating and cooling cycles. Weight gains occurring during isothermal scale-growth processes have been well characterized as being parabolic or nearly parabolic functions of time because diffusion controls reaction rates. In contrast, the net weight change in cyclic oxidation is the sum of the effects of the growth and spallation of scale. Typically, the net weight gain in cyclic oxidation is determined only empirically (that is, by measurement), with no unique or straightforward mathematical connection to either the rate of growth or the amount of metal consumed. Thus, there is a need for mathematical modeling to infer spallation mechanisms. COSP is a computer program that models the growth and spallation processes of cyclic oxidation on the basis of a few elementary assumptions that were discussed in COSP: A Computer Model of Cyclic Oxidation, Oxidation of Metals, vol. 36, numbers 1 and 2, 1991, pages 81-112. Inputs to the model include the selection of an oxidation-growth law and a spalling geometry, plus oxide-phase, growth-rate, cycle-duration, and spall-constant parameters. (The spalling fraction is often shown to be a constant factor times the existing amount of scale.) The output of COSP includes the net change in weight, the amounts of retained and spalled oxide, the total amounts of oxygen and metal

Monopod bucket foundations under cyclic lateral loading

DEFF Research Database (Denmark)

Foglia, Aligi; Ibsen, Lars Bo

on bucket foundations under lateral cyclic loading. The test setup is described in detail and a comprehensive experimental campaign is presented. The foundation is subjected to cyclic overturning moment, cyclic horizontal loading and constant vertical loading, acting on the same plane for thousands...

Stimulation of prostaglandin E2 production by phorbol esters and epidermal growth factor in porcine thyroid cells

International Nuclear Information System (INIS)

Kasai, K.; Hiraiwa, M.; Emoto, T.; Akimoto, K.; Takaoka, T.; Shimoda, S.I.

1987-01-01

Effects of phorbol esters and epidermal growth factor (EGF) on prostaglandin E 2 production by cultured porcine thyroid cells were examined. Both phorbol 12-myristate 13-acetate (PMA) and EGF stimulated prostaglandin E 2 production by the cells in dose related fashion. PMA stimulated prostaglandin E 2 production over fifty-fold with the dose of 10 -7 M compared with control. EGF (10 -7 M) also stimulated it about ten-fold. The ED 50 values of PMA and EGF were respectively around 1 x 10 -9 M and 5 x 10 -10 M. Thyroid stimulating hormone (TSH), however, did not stimulate prostaglandin E 2 production from 1 to 24-h incubation. The release of radioactivity from [ 3 H]-arachidonic acid prelabeled cells was also stimulated by PMA and EGF, but not by TSH. These results indicate that both PMA and EGF are potent stimulators of prostaglandin E 2 production, associated with the activity to stimulate arachidonic acid release in porcine thyroid cells. 36 references, 2 figures, 1 table

Generalized Wideband Cyclic MUSIC

Directory of Open Access Journals (Sweden)

Zhang-Meng Liu

2009-01-01

Full Text Available The method of Spectral Correlation-Signal Subspace Fitting (SC-SSF fails to separate wideband cyclostationary signals with coherent second-order cyclic statistics (SOCS. Averaged Cyclic MUSIC (ACM method made up for the drawback to some degree via temporally averaging the cyclic cross-correlation of the array output. This paper interprets ACM from another perspective and proposes a new DOA estimation method by generalizing ACM for wideband cyclostationary signals. The proposed method successfully makes up for the aforementioned drawback of SC-SSF and obtains a more satisfying performance than ACM. It is also demonstrated that ACM is a simplified form of the proposed method when only a single spectral frequency is exploited, and the integration of the frequencies within the signal bandwidth helps the new method to outperform ACM.

Interferon γ-inducible protein (IFI) 16 transcriptionally regulates type i interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses.

Science.gov (United States)

Thompson, Mikayla R; Sharma, Shruti; Atianand, Maninjay; Jensen, Søren B; Carpenter, Susan; Knipe, David M; Fitzgerald, Katherine A; Kurt-Jones, Evelyn A

2014-08-22

The interferon γ-inducible protein 16 (IFI16) has recently been linked to the detection of nuclear and cytosolic DNA during infection with herpes simplex virus-1 and HIV. IFI16 binds dsDNA via HIN200 domains and activates stimulator of interferon genes (STING), leading to TANK (TRAF family member-associated NF-κB activator)-binding kinase-1 (TBK1)-dependent phosphorylation of interferon regulatory factor (IRF) 3 and transcription of type I interferons (IFNs) and related genes. To better understand the role of IFI16 in coordinating type I IFN gene regulation, we generated cell lines with stable knockdown of IFI16 and examined responses to DNA and RNA viruses as well as cyclic dinucleotides. As expected, stable knockdown of IFI16 led to a severely attenuated type I IFN response to DNA ligands and viruses. In contrast, expression of the NF-κB-regulated cytokines IL-6 and IL-1β was unaffected in IFI16 knockdown cells, suggesting that the role of IFI16 in sensing these triggers was unique to the type I IFN pathway. Surprisingly, we also found that knockdown of IFI16 led to a severe attenuation of IFN-α and the IFN-stimulated gene retinoic acid-inducible gene I (RIG-I) in response to cyclic GMP-AMP, a second messenger produced by cyclic GMP-AMP synthase (cGAS) as well as RNA ligands and viruses. Analysis of IFI16 knockdown cells revealed compromised occupancy of RNA polymerase II on the IFN-α promoter in these cells, suggesting that transcription of IFN-stimulated genes is dependent on IFI16. These results indicate a broader role for IFI16 in the regulation of the type I IFN response to RNA and DNA viruses in antiviral immunity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

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Shi-qi An

2014-10-01

Full Text Available Bis-(3',5' cyclic di-guanylate (cyclic di-GMP is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc. This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d∼2 µM. Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

Pro-inflammatory stimulation of meniscus cells increases production of matrix metalloproteinases and additional catabolic factors involved in osteoarthritis pathogenesis

Science.gov (United States)

Stone, Austin V.; Loeser, Richard F.; Vanderman, Kadie S.; Long, David L.; Clark, Stephanie C.; Ferguson, Cristin M.

2014-01-01

Objective Meniscus injury increases the risk of osteoarthritis; however, the biologic mechanism remains unknown. We hypothesized that pro-inflammatory stimulation of meniscus would increase production of matrix-degrading enzymes, cytokines and chemokines which cause joint tissue destruction and could contribute to osteoarthritis development. Design Meniscus and cartilage tissue from healthy tissue donors and total knee arthroplasties was cultured. Primary cell cultures were stimulated with pro-inflammatory factors [IL-1β, IL-6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real-time PCR, protein arrays and immunoblots. To determine if NF-κB was required for MMP production, meniscus cultures were treated with inflammatory factors with and without the NF-κB inhibitor, hypoestoxide. Results Normal and osteoarthritic meniscus cells increased their MMP secretion in response to stimulation, but specific patterns emerged that were unique to each stimulus with the greatest number of MMPs expressed in response to FnF. Meniscus collagen and connective tissue growth factor gene expression was reduced. Expression of cytokines (IL-1α, IL-1β, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and components of the NF-κB and tumor necrosis factor (TNF) family were significantly increased. Cytokine and chemokine protein production was also increased by stimulation. When primary cell cultures were treated with hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was reduced as were MMP-1 and MMP-3 production. Conclusions Pro-inflammatory stimulation of meniscus cells increased matrix metalloproteinase production and catabolic gene expression. The meniscus could have an active biologic role in osteoarthritis development following joint injury through increased production of cytokines, chemokines, and matrix-degrading enzymes. PMID:24315792

Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

Science.gov (United States)

Tal, Reshef; Seifer, David B; Grazi, Richard V; Malter, Henry E

2014-08-20

Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

Virtual screening using combinatorial cyclic peptide libraries reveals protein interfaces readily targetable by cyclic peptides.

Science.gov (United States)

Duffy, Fergal J; O'Donovan, Darragh; Devocelle, Marc; Moran, Niamh; O'Connell, David J; Shields, Denis C

2015-03-23

Protein-protein and protein-peptide interactions are responsible for the vast majority of biological functions in vivo, but targeting these interactions with small molecules has historically been difficult. What is required are efficient combined computational and experimental screening methods to choose among a number of potential protein interfaces worthy of targeting lead macrocyclic compounds for further investigation. To achieve this, we have generated combinatorial 3D virtual libraries of short disulfide-bonded peptides and compared them to pharmacophore models of important protein-protein and protein-peptide structures, including short linear motifs (SLiMs), protein-binding peptides, and turn structures at protein-protein interfaces, built from 3D models available in the Protein Data Bank. We prepared a total of 372 reference pharmacophores, which were matched against 108,659 multiconformer cyclic peptides. After normalization to exclude nonspecific cyclic peptides, the top hits notably are enriched for mimetics of turn structures, including a turn at the interaction surface of human α thrombin, and also feature several protein-binding peptides. The top cyclic peptide hits also cover the critical "hot spot" interaction sites predicted from the interaction crystal structure. We have validated our method by testing cyclic peptides predicted to inhibit thrombin, a key protein in the blood coagulation pathway of important therapeutic interest, identifying a cyclic peptide inhibitor with lead-like activity. We conclude that protein interfaces most readily targetable by cyclic peptides and related macrocyclic drugs may be identified computationally among a set of candidate interfaces, accelerating the choice of interfaces against which lead compounds may be screened.

Cyclic Voltammetry of Biopolymer Heparin at PVC Plasticized Liquid Membrane

Czech Academy of Sciences Publication Activity Database

Samec, Zdeněk; Trojánek, Antonín; Langmaier, Jan; Samcová, E.

2003-01-01

Roč. 5, - (2003), s. 867-870 ISSN 1388-2481 R&D Projects: GA ČR GA203/04/0424 Institutional research plan: CEZ:AV0Z4040901 Keywords : cyclic voltammetry * PVC plasticized liquit membrane * heparin Subject RIV: CG - Electrochemistry Impact factor: 2.300, year: 2003

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

Energy Technology Data Exchange (ETDEWEB)

Taub, Mary, E-mail: biochtau@buffalo.edu

2016-03-11

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

International Nuclear Information System (INIS)

Taub, Mary

2016-01-01

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10"−"5 M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

Damage assessment of low-cycle fatigue by crack growth prediction. Fatigue life under cyclic thermal stress

International Nuclear Information System (INIS)

Kamaya, Masayuki

2013-01-01

The number of cycles to failure of specimens in fatigue tests can be estimated by predicting crack growth. Under a cyclic thermal stress caused by fluctuation of fluid temperature, due to the stress gradient in the thickness direction, the estimated fatigue life differs from that estimated for mechanical fatigue tests. In this paper, the influence of crack growth under cyclic thermal loading on the fatigue life was investigated. First, the thermal stress was derived by superposing analytical solutions, and then, the stress intensity factor was obtained by the weight function method. It was shown that the thermal stress depended not on the rate of the fluid temperature change but on the rise time, and the magnitude of the stress was increased as the rise time was decreased. The stress intensity factor under the cyclic thermal stress was smaller than that under the uniform stress distribution. The change in the stress intensity factor with the crack depth did not depend on the heat transfer coefficient and only slightly depended on the rise time. The estimated fatigue life under the cyclic thermal loading could be 1.6 times longer than that under the uniform stress distribution. The critical size for the fatigue life determination was assumed to be 3 mm for fatigue test specimens of 10 mm diameter. By evaluating the critical size by structural integrity analyses, the fatigue life was increased and the effect of the critical size on the fatigue life was more pronounced for the cyclic thermal stress. (author)

21 CFR 862.1230 - Cyclic AMP test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cyclic AMP test system. 862.1230 Section 862.1230....1230 Cyclic AMP test system. (a) Identification. A cyclic AMP test system is a device intended to measure the level of adenosine 3′, 5′-monophosphate (cyclic AMP) in plasma, urine, and other body fluids...

Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes

OpenAIRE

Wang, Yan; Su, Guo-Hua; Zhang, Fang; Chu, Jing-Xue; Wang, Yun-Shan

2015-01-01

Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdow...

Cyclic delivery scheduling to customers with different priorities

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Katarzyna Zofia Gdowska

2013-12-01

Full Text Available Background: In this paper a cyclic delivery scheduling problem for customers with different priorities is presented. Shops, which are provided with deliveries, are occasionally located in places which are crucial for the proper flow of traffic. In such places coordination of deliveries is crucial; therefore it allows to completely eliminate the phenomenon of the simultaneous arrivals of suppliers. Methods: In this paper the cyclic delivery scheduling problem for customers with different priorities was presented. To this theoretical problem a mix integer programming model was developed. Specific approach to the cyclic delivery scheduling problem is inspired by timetabling problem for urban public transport. Results: Mixed integer programming model was employed for solving four cases of cyclic delivery scheduling problem for customers with different priorities. When the value of the synchronization priority assigned to a single customer raised then the total number of synchronizations in the whole network decreased. In order to compare solutions a synchronization rate was utilized. A simple factor was utilized - the proportion of number of synchronizations of deliveries to a given customer to the total number of synchronizations obtained for the whole network. When the value of synchronization priority raised then the value of synchronization rate of this customer improved significantly. Conclusions: The mixed integer programming model for the cyclic delivery scheduling problem for customers with different priorities presented in this paper can be utilized for generating schedules of serving customers located in places where only one delivery can be received and unloaded at one go and where there is no space for other suppliers to wait in a queue. Such a schedule can be very useful for organizing deliveries to small shops united in a franchising network, since they operate in a way that is very similar to the network presented in this paper

Aggressive cutaneous vasculitis in a patient with chronic lymphatic leukemia following granulocyte colony stimulating factor injection: a case report

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El Husseiny Noha M

2011-03-01

Full Text Available Abstract Introduction Vasculitis has been reported in a few cases of chronic lymphatic leukemia and with granulocytic colony-stimulating factor therapy. Those with granulocytic colony-stimulating factor occurred after prolonged therapy and there was a rise in total leukocyte count unlike that in our patient who received just a single injection for the first time. Case presentation We report the case of a 64-year-old Egyptian man with chronic lymphatic leukemia who developed progressive cutaneous vasculitic lesions following injection of a single dose of a granulocytic colony stimulating factor before a third cycle of chemotherapy to improve neutropenia. This is an unusual case and the pathogenesis is not fully understood. Our patient was not on any medical treatment except for bisoprolol for ischemic heart disease. Although aggressive management with steroids, anticoagulation and plasmapheresis had been carried out, the condition was aggressive and the patient's consciousness deteriorated. A magnetic resonance imaging scan of his brain revealed multiple ischemic foci that could be attributed to vasculitis of the brain. Conclusion The aim of this case report is to highlight the importance of monitoring patients on granulocytic colony-stimulating factor therapy, especially in the context of other conditions (such as a hematological malignancy that may lead to an adverse outcome.

Effect of loading history on cyclic stress-strain response

Czech Academy of Sciences Publication Activity Database

Kunz, Ludvík; Lukáš, Petr; Weiss, B.; Melisova, D.

2001-01-01

Roč. 314, 1/2 (2001), s. 1-6 ISSN 0921-5093. [TMS Annual Meeting. Nashville, 12.03.2000-16.03.2000] R&D Projects: GA AV ČR IBS2041001 Institutional research plan: CEZ:AV0Z2041904 Keywords : cyclic plasticity * loading history * mean stress Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.978, year: 2001

Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells

DEFF Research Database (Denmark)

Tratwal, Josefine; Mathiasen, Anders Bruun; Juhl, Morten

2015-01-01

INTRODUCTION: Stimulation of mesenchymal stromal cells and adipose tissue-derived stromal cells (ASCs) with vascular endothelial growth factor (VEGF) has been used in multiple animal studies and clinical trials for regenerative purposes. VEGF stimulation is believed to promote angiogenesis and VEGF...... stimulation is usually performed under serum deprivation. Potential regenerative molecular mechanisms are numerous and the role of contributing factors is uncertain. The aim of the current study was to investigate the effect of in vitro serum deprivation and VEGF stimulation on gene expression patterns...... of ASCs. METHODS: Gene expressions of ASCs cultured in complete medium, ASCs cultured in serum-deprived medium and ASCs stimulated with VEGF in serum-deprived medium were compared. ASC characteristics according to criteria set by the International Society of Cellular Therapy were confirmed by flow...

Behaviour of Cohesionless Soils During Cyclic Loading

DEFF Research Database (Denmark)

Shajarati, Amir; Sørensen, Kris Wessel; Nielsen, Søren Kjær

Offshore wind turbine foundations are typically subjected to cyclic loading from both wind and waves, which can lead to unacceptable deformations in the soil. However, no generally accepted standardised method is currently available, when accounting for cyclic loading during the design of offshore...... wind turbine foundations. Therefore a literature study is performed in order to investigate existing research treating the behaviour of cohesionless soils, when subjected to cyclic loading. The behaviour of a soil subjected to cyclic loading is found to be dependent on; the relative density, mean...

Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor

International Nuclear Information System (INIS)

Matsumoto, K.; Hashimoto, K.; Yoshikawa, K.; Nakamura, T.

1991-01-01

Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes

Markup cyclicality, employment adjustment, and financial constraints

OpenAIRE

Askildsen, Jan Erik; Nilsen, Øivind Anti

2001-01-01

We investigate the existence of markups and their cyclical behaviour. Markup is not directly observed. Instead, it is given as a price-cost relation that is estimated from a dynamic model of the firm. The model incorporates potential costly employment adjustments and takes into consideration that firms may be financially constrained. When considering size of the future labour stock, financially constrained firms may behave as if they have a higher discount factor, which may affect the realise...

Exploring bikeability in a metropolitan setting: stimulating and hindering factors in commuting route environments

Directory of Open Access Journals (Sweden)

Wahlgren Lina

2012-03-01

Full Text Available Abstract Background Route environments may influence people's active commuting positively and thereby contribute to public health. Assessments of route environments are, however, needed in order to better understand the possible relationship between active commuting and the route environment. The aim of this study was, therefore, to assess the potential associations between perceptions of whether the route environment on the whole hinders or stimulates bicycle commuting and perceptions of environmental factors. Methods The Active Commuting Route Environment Scale (ACRES was used for the assessment of bicycle commuters' perceptions of their route environments in the inner urban parts of Greater Stockholm, Sweden. Bicycle commuters (n = 827 were recruited by advertisements in newspapers. Simultaneous multiple regression analyses were used to assess the relation between predictor variables (such as levels of exhaust fumes, noise, traffic speed, traffic congestion and greenery and the outcome variable (hindering - stimulating route environments. Two models were run, (Model 1 without and (Model 2 with the item traffic: unsafe or safe included as a predictor. Results Overall, about 40% of the variance of hindering - stimulating route environments was explained by the environmental predictors in our models (Model 1, R2 = 0.415, and Model 2, R 2= 0.435. The regression equation for Model 1 was: y = 8.53 + 0.33 ugly or beautiful + 0.14 greenery + (-0.14 course of the route + (-0.13 exhaust fumes + (-0.09 congestion: all types of vehicles (p ≤ 0.019. The regression equation for Model 2 was y = 6.55 + 0.31 ugly or beautiful + 0.16 traffic: unsafe or safe + (-0.13 exhaust fumes + 0.12 greenery + (-0.12 course of the route (p ≤ 0.001. Conclusions The main results indicate that beautiful, green and safe route environments seem to be, independently of each other, stimulating factors for bicycle commuting in inner urban areas. On the other hand, exhaust

Cyclic nucleotide dependent dephosphorylation of regulator of G-protein signaling 18 in human platelets.

LENUS (Irish Health Repository)

Gegenbauer, Kristina

2013-11-01

Regulator of G-protein signaling 18 (RGS18) is a GTPase-activating protein that turns off Gq signaling in platelets. RGS18 is regulated by binding to the adaptor protein 14-3-3 via phosphorylated serine residues S49 and S218 on RGS18. In this study we confirm that thrombin, thromboxane A2, or ADP stimulate the interaction of RGS18 and 14-3-3 by increasing the phosphorylation of S49. Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. To understand the effect of S216 phosphorylation we studied the phosphorylation kinetics of S49, S216, and S218 using Phos-tag gels and phosphorylation site-specific antibodies in transfected cells and in platelets. Cyclic nucleotide-induced detachment of 14-3-3 from RGS18 coincides initially with double phosphorylation of S216 and S218. This is followed by dephosphorylation of S49 and S218. Dephosphorylation of S49 and S218 might be mediated by protein phosphatase 1 (PP1) which is linked to RGS18 by the regulatory subunit PPP1R9B (spinophilin). We conclude that PKA and PKG induced S216 phosphorylation triggers the dephosphorylation of the 14-3-3 binding sites of RGS18 in platelets.

Granulocyte-macrophage colony-stimulating factor amplification of interleukin-1beta and tumor necrosis factor alpha production in THP-1 human monocytic cells stimulated with lipopolysaccharide of oral microorganisms.

Science.gov (United States)

Baqui, A A; Meiller, T F; Chon, J J; Turng, B F; Falkler, W A

1998-05-01

Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) play important roles in inflammatory processes, including exacerbation of periodontal diseases, one of the most common complications in patients who undergo this therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1beta and TNF-alpha production following GM-CSF supplementation with lipopolysaccharide (LPS) from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium nucleatum. LPS of P. gingivalis or F. nucleatum was prepared by a phenol-water extraction method and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and determination of total protein and endotoxin contents. Resting THP-1 cells were treated with LPS of P. gingivalis or F. nucleatum and/or GM-CSF (50 IU/ml) by using different concentrations for various time periods. Production of IL-1beta and TNF-alpha in THP-1 cells was measured by solid-phase enzyme-linked immunosorbent assay. Reverse transcription (RT)-PCR was used to evaluate the gene expression of resting and treated THP-1 cells. IL-1beta was not detected in untreated THP-1 cells. IL-1beta production was, however, stimulated sharply at 4 h. GM-CSF amplified IL-1beta production in THP-1 cells treated with LPS from both oral anaerobes. No IL-1beta-specific mRNA transcript was detected in untreated THP-1 cells. However, IL-1beta mRNA was detected by RT-PCR 2 h after stimulation of THP-1 cells with LPS from both organisms. GM-CSF did not shorten the IL-1beta transcriptional activation time. GM-CSF plus F. nucleatum or P. gingivalis LPS activated THP-1 cells to produce a 1.6-fold increase in TNF-alpha production at 4 h over LPS stimulation alone. These investigations with the in vitro THP-1 model indicate that there may be an increase in the cellular immune response to oral

On Improvements of Cyclic MUSIC

Directory of Open Access Journals (Sweden)

H. Howard Fan

2005-01-01

Full Text Available Many man-made signals encountered in communications exhibit cyclostationarity. By exploiting cyclostationarity, cyclic MUSIC has been shown to be able to separate signals with different cycle frequencies, thus, to be able to perform signal selective direction of-arrival (DOA estimation. However, as will be shown in this paper, the DOA estimation of cyclic MUSIC is actually biased. We show in this paper that by properly choosing the frequency for evaluating the steering vector, the bias of DOA estimation can be substantially reduced and the performance can be improved. Furthermore, we propose another algorithm exploiting cyclic conjugate correlation to further improve the performance of DOA estimation. Simulation results show the effectiveness of both of our methods.

Effect of laser parameters on surface roughness of laser modified tool steel after thermal cyclic loading

Science.gov (United States)

Lau Sheng, Annie; Ismail, Izwan; Nur Aqida, Syarifah

2018-03-01

This study presents the effects of laser parameters on the surface roughness of laser modified tool steel after thermal cyclic loading. Pulse mode Nd:YAG laser was used to perform the laser surface modification process on AISI H13 tool steel samples. Samples were then treated with thermal cyclic loading experiments which involved alternate immersion in molten aluminium (800°C) and water (27°C) for 553 cycles. A full factorial design of experiment (DOE) was developed to perform the investigation. Factors for the DOE are the laser parameter namely overlap rate (η), pulse repetition frequency (f PRF) and peak power (Ppeak ) while the response is the surface roughness after thermal cyclic loading. Results indicate the surface roughness of the laser modified surface after thermal cyclic loading is significantly affected by laser parameter settings.

Salivary gland ultrastructure and cyclic AMP-dependent reactions in Spacelab 3 rats

International Nuclear Information System (INIS)

Mednieks, M.I.; Hand, A.R.

1987-01-01

Environmental stimuli influencing catecholamine levels induce changes in cyclic AMP-dependent reactions and cell morphology in the rat parotid. Responses of salivary glands to spaceflight were determined by measurement of cyclic AMP-mediated reactions in fresh-frozen salivary glands and by microscopic evaluation of ultrastructure in fixed parotid glands. Decreased cell-free protein phosphorylation, determined by autoradiography, occurred in parotid glands in three of five flight animals. Protein kinase activity ratios were decreased in the soluble and increased in the particulate fractions of Spacelab 3 (SL-3) rat sublingual glands, compared with ground controls. Biochemical analyses show that effects of space flight on salivary glands are similar to those induced experimentally by physiological manipulation or alteration of catecholamine levels. Morphological evaluation of three SL-3 rat parotid glands showed increased numbers of lysosomes, autophagic vacuoles containing degenerating secretory product, and accumulation of lipid droplets. Since these animals lost weight, consistent with disruption of food and water consumption, morphological changes may in part be due to decreased masticatory stimulation, as occurs with reduced food intake or a liquid diet. The observed changes may reflect physiological responses of the gastrointestinal and autonomic systems to effects of spaceflight

Regulation of the sodium/potassium/chloride cotransporter by calcium and cyclic AMP in cultured vascular smooth muscle cells

International Nuclear Information System (INIS)

Higgins, B.L.; Smith, L.; Smith, J.B.

1987-01-01

The activity of the Na/K/Cl cotransporter in smooth muscle cells cultured from rat aorta was assayed by measuring the initial rate of furosemide-inhibitable 86 Rb influx or efflux. Five uM furosemide or 0.2 uM bumetanide inhibited influx by 50%. Furosemide-inhibitable 86 Rb influx depended on the presence of all 3 ions in the external medium. The dependence on Na and K was hyperbolic with apparent Km values of 45 and 5 mM, respectively. The dependence on Cl was sigmoidal. Assuming a stoichiometry of 1:1:2 for Na:K:Cl, a Km for Cl of 60 mM was obtained from a Hofstee plot of the data. Rapidly growing cells had 3 fold higher cotransport activity than quiescent cells. Angiotensin II (ANG) stimulated furosemide-inhibitable 86 Rb efflux by 2 fold. An ANG receptor antagonist prevented ANG from increasing cotransport activity. Two calcium ionophores, A23187 and ionomycin, increased cotransport activity by 2 fold. Phorbol myristate acetate had no effect on cotransport activity. Isoproterenol, dibutyryl cyclic AMP, cholera toxin, or methylisobutylxanthine inhibited furosemide-sensitive 86 Rb influx by 35 to 50%. From these findings they conclude that increasing cytoplasmic free calcium stimulates cotransport activity, whereas increasing cellular cyclic AMP inhibits the cotransporter

Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells.

Science.gov (United States)

Fearnley, Gareth W; Smith, Gina A; Odell, Adam F; Latham, Antony M; Wheatcroft, Stephen B; Harrison, Michael A; Tomlinson, Darren C; Ponnambalam, Sreenivasan

2014-01-01

The vascular endothelial growth factor A (VEGF-A) is a multifunctional cytokine that stimulates blood vessel sprouting, vascular repair, and regeneration. VEGF-A binds to VEGF receptor tyrosine kinases (VEGFRs) and stimulates intracellular signaling leading to changes in vascular physiology. An important aspect of this phenomenon is the spatiotemporal coordination of VEGFR trafficking and intracellular signaling to ensure that VEGFR residence in different organelles is linked to downstream cellular outputs. Here, we describe a series of assays to evaluate the effects of VEGF-A-stimulated intracellular signaling from intracellular compartments such as the endosome-lysosome system. These assays include the initial isolation and characterization of primary human endothelial cells, performing reverse genetics for analyzing protein function; methods used to study receptor trafficking, signaling, and proteolysis; and assays used to measure changes in cell migration, proliferation, and tubulogenesis. Each of these assays has been exemplified with studies performed in our laboratories. In conclusion, we describe necessary techniques for studying the role of VEGF-A in endothelial cell function. © 2014 Elsevier Inc. All rights reserved.

Statistical damage constitutive model for rocks subjected to cyclic stress and cyclic temperature

Science.gov (United States)

Zhou, Shu-Wei; Xia, Cai-Chu; Zhao, Hai-Bin; Mei, Song-Hua; Zhou, Yu

2017-10-01

A constitutive model of rocks subjected to cyclic stress-temperature was proposed. Based on statistical damage theory, the damage constitutive model with Weibull distribution was extended. Influence of model parameters on the stress-strain curve for rock reloading after stress-temperature cycling was then discussed. The proposed model was initially validated by rock tests for cyclic stress-temperature and only cyclic stress. Finally, the total damage evolution induced by stress-temperature cycling and reloading after cycling was explored and discussed. The proposed constitutive model is reasonable and applicable, describing well the stress-strain relationship during stress-temperature cycles and providing a good fit to the test results. Elastic modulus in the reference state and the damage induced by cycling affect the shape of reloading stress-strain curve. Total damage induced by cycling and reloading after cycling exhibits three stages: initial slow increase, mid-term accelerated increase, and final slow increase.

Ex Vivo Assay of Electrical Stimulation to Rat Sciatic Nerves: Cell Behaviors and Growth Factor Expression.

Science.gov (United States)

Du, Zhiyong; Bondarenko, Olexandr; Wang, Dingkun; Rouabhia, Mahmoud; Zhang, Ze

2016-06-01

Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities. © 2015 Wiley Periodicals, Inc.

Cyclic adenosine monophosphate levels and the function of skin microvascular endothelial cells.

Science.gov (United States)

Tuder, R M; Karasek, M A; Bensch, K G

1990-02-01

The maintenance of the normal epithelioid morphology of human dermal microvascular endothelial cells (MEC) grown in vitro depends strongly on the presence of factors that increase intracellular levels of cyclic AMP. Complete removal of dibutyryl cAMP and isobutylmethylxanthine (IMX) from the growth medium results in a progressive transition from an epithelioid to a spindle-shaped cell line. This transition cannot be reversed by the readdition of dibutyryl cAMP and IMX to the growth medium or by addition of agonists that increase cAMP levels. Spindle-shaped MEC lose the ability to express Factor VIII rAG and DR antigens and to bind peripheral blood mononuclear leukocyte (PBML). Ultrastructural analyses of transitional cells and spindle-shaped cells show decreased numbers of Weibel-Palade bodies in transitional cells and their complete absence in spindle-shaped cells. Interferon-gamma alters several functional properties of both epithelioid and spindle-shaped cells. In the absence of dibutyryl cAMP it accelerates the transition from epithelial to spindle-shaped cells, whereas in the presence of cyclic AMP interferon-gamma increases the binding of PBMLs to both epithelioid and spindle-shaped MEC and the endocytic activity of the endothelial cells. These results suggest that cyclic AMP is an important second messenger in the maintenance of several key functions of microvascular endothelial cells. Factors that influence the levels of this messenger in vivo can be expected to influence the angiogenic and immunologic functions of the microvasculature.

Cyclic deformation of zircaloy-4 at room temperature

International Nuclear Information System (INIS)

Armas, A. F; Herenu, S; Bolmaro, R; Alvarez-Armas, I

2003-01-01

Annealed materials hardens under low cyclic fatigue tests.However, FCC metals tested with medium strain amplitudes show an initial cyclic softening.That behaviour is related with the strong interstitial atom-dislocation interactions.For HCP materials the information is scarce.Commercial purity Zirconium and Zircaloy-4 alloys show also a pronounced cyclic softening, similar to Titanium alloys.Recently the rotation texture induced softening model has been proposed according to which the crystals are placed in a more favourable deformation orientation by prismatic slip due to the cyclic strain.The purpose of the current paper is the presentation of decisive results to discuss the causes for cyclic softening of Zircaloy-4. Low cycle fatigue tests were performed on recrystallized Zircaloy-4 samples.The cyclic behaviour shows an exponential softening at room temperature independently of the deformation range.Only at high temperature a cyclic hardening is shown at low number of cycles.Friction stresses, related with dislocation movement itself, and back stresses, related with dislocation pile-ups can be calculated from the stress-strain loops.The cyclic softening is due to diminishing friction stress while the starting hardening behaviour is due to increasing back stresses.The rotation texture induced softening model is ruled out assuming instead a model based on dislocation unlocking from interstitial oxygen solute atoms

Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells.

Science.gov (United States)

Montgomery, M D; Bylund, D B

2010-02-01

The alpha(2C)-adrenoceptor has multiple functions, including inhibiting release of noradrenaline from presynaptic nerve terminals. A human alpha(2C) polymorphism, Del322-325, a potential risk factor for heart failure, has been reported to exhibit reduced signalling in CHO cells. To further understand the role of the Del322-325 polymorphism on receptor signalling, we attempted to replicate and further study the reduced signalling in HEK293 cells. Human alpha(2C) wild-type (WT) and Del322-325 adrenoceptors were stably transfected into HEK293 cells. Radioligand binding was performed to determine affinities for both receptors. In intact cells, inhibition of forskolin-stimulated cyclic AMP production by WT and Del322-325 clones with a range of receptor densities (200-2320 fmol.mg(-1) protein) was measured following agonist treatment. Noradrenaline, brimonidine and clonidine exhibited similar binding affinities for WT and Del322-325. Brimonidine and clonidine also had similar efficacies and potencies for both receptors for the inhibition of cyclic AMP production at all receptor densities tested. A linear regression analysis comparing efficacy and potency with receptor expression levels showed no differences in slopes between WT and Del322-325. The alpha(2C) WT and Del322-325 adrenoceptors exhibited similar binding properties. Additionally, inhibition of cyclic AMP production by Del322-325 was similar to that of WT over a range of receptor densities. Therefore, in intact HEK293 cells, the alpha(2C)-Del322-325 polymorphism does not exhibit reduced signalling to adenylyl cyclase and may not represent a clinically important phenotype.

Rhizobial Nodulation Factors Stimulate Mycorrhizal Colonization of Nodulating and Nonnodulating Soybeans.

Science.gov (United States)

Xie, Z. P.; Staehelin, C.; Vierheilig, H.; Wiemken, A.; Jabbouri, S.; Broughton, W. J.; Vogeli-Lange, R.; Boller, T.

1995-08-01

Legumes form tripartite symbiotic associations with noduleinducing rhizobia and vesicular-arbuscular mycorrhizal fungi. Co-inoculation of soybean (Glycine max [L.] Merr.) roots with Bradyrhizobium japonicum 61-A-101 considerably enhanced colonization by the mycorrhizal fungus Glomus mosseae. A similar stimulatory effect on mycorrhizal colonization was also observed in nonnodulating soybean mutants when inoculated with Bradyrhizobium japonicum and in wild-type soybean plants when inoculated with ineffective rhizobial strains, indicating that a functional rhizobial symbiosis is not necessary for enhanced mycorrhiza formation. Inoculation with the mutant Rhizobium sp. NGR[delta]nodABC, unable to produce nodulation (Nod) factors, did not show any effect on mycorrhiza. Highly purified Nod factors also increased the degree of mycorrhizal colonization. Nod factors from Rhizobium sp. NGR234 differed in their potential to promote fungal colonization. The acetylated factor NodNGR-V (MeFuc, Ac), added at concentrations as low as 10-9 M, was active, whereas the sulfated factor, NodNGR-V (MeFuc, S), was inactive. Several soybean flavonoids known to accumulate in response to the acetylated Nod factor showed a similar promoting effect on mycorrhiza. These results suggest that plant flavonoids mediate the Nod factor-induced stimulation of mycorrhizal colonization in soybean roots.

Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis.

Science.gov (United States)

Collins, Angela C; Cai, Haocheng; Li, Tuo; Franco, Luis H; Li, Xiao-Dong; Nair, Vidhya R; Scharn, Caitlyn R; Stamm, Chelsea E; Levine, Beth; Chen, Zhijian J; Shiloh, Michael U

2015-06-10

Activation of the DNA-dependent cytosolic surveillance pathway in response to Mycobacterium tuberculosis infection stimulates ubiquitin-dependent autophagy and inflammatory cytokine production, and plays an important role in host defense against M. tuberculosis. However, the identity of the host sensor for M. tuberculosis DNA is unknown. Here we show that M. tuberculosis activated cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) in macrophages to produce cGAMP, a second messenger that activates the adaptor protein stimulator of interferon genes (STING) to induce type I interferons and other cytokines. cGAS localized with M. tuberculosis in mouse and human cells and in human tuberculosis lesions. Knockdown or knockout of cGAS in human or mouse macrophages blocked cytokine production and induction of autophagy. Mice deficient in cGAS were more susceptible to lethality caused by infection with M. tuberculosis. These results demonstrate that cGAS is a vital innate immune sensor of M. tuberculosis infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Granulocyte colony-stimulating factor protects mice during respiratory virus infections.

Directory of Open Access Journals (Sweden)

Tamar Hermesh

Full Text Available A burst in the production of pro-inflammatory molecules characterizes the beginning of the host response to infection. Cytokines, chemokines, and growth factors work in concert to control pathogen replication and activate innate and adaptive immune responses. Granulocyte colony-stimulating factor (G-CSF mobilizes and activates hematopoietic cells from the bone marrow, and it has been shown to mediate the generation of effective immunity against bacterial and fungal infections. G-CSF is produced at high levels in the lungs during infection with influenza and parainfluenza viruses, but its role during these infections is unknown. Here we show that during infection of mice with a non-lethal dose of influenza or Sendai virus, G-CSF promotes the accumulation of activated Ly6G+ granulocytes that control the extent of the lung pro-inflammatory response. Remarkably, these G-CSF-mediated effects facilitate viral clearance and sustain mouse survival.

The Effect Of Anisotropy In Formation Permeability On The Efficiency Of Cyclic Water Flooding

Directory of Open Access Journals (Sweden)

Al-Obaidi SH

2017-11-01

Full Text Available In oil industry one of the most worldwide used methods a among the hydrodynamic enhanced oil recovery methods is the water flooding including the cyclic water flooding. The efficiency of cyclic water flooding is affected by a number of geophysical and field technological factors. In this work and based on three-dimensional hydrodynamic simulation it is shown that anisotropy of formation permeability has significant effect on justification of the half-cycle time and the technological effectiveness of the method.

Examination of influencing factors on cyclic crack growth behaviour of cracked components. Final report; Untersuchung von Einflussfaktoren auf das zyklische Risswachstum angerissener Bauteile. Abschlussbericht

Energy Technology Data Exchange (ETDEWEB)

Soppa, Ewa Anna; Silcher, Horst

2015-01-31

Fatigue crack growth of short and long cracks was investigated for both materials: the Nb-stabilized austenitic stainless steel X6 CrNiNb 18-10 and the ferritic-bainitic steel 22 NiMoCr 3-7. These both steels belong to the materials in the primary circuit of german power plants. For a reliable estimation of the lifetime of components subject to cyclic fatigue a detailed knowledge of the phenomena accompanying fatigue processes and which cause both - initiation and growth of fatigue cracks is essential. The deformation induced transformation of austenite into α'-martensite at room temperature is thus very important in the initiation and growth of fatigue cracks. Because these processes are manifest at first at the microlevel, the use of methods which reveal information at high resolution is of significant importance. In order to study the initiation and growth of short cracks, cylindrical smooth specimens, compact tension C(T)- and modified C(T)-specimens have been used. Cyclic crack propagation of long cracks was investigated on compact tension C(T)-specimens with W=50 mm and B=10 mm. The SEM, TEM and EBSD technique are powerful methods for determining crystallographic orientation, for the identification of individual phases and for recealing plastic deformation. They were used for analyses of microcracks in combination with interrupted cyclic tests. The impact of crack closure on the threshold parameter ΔK{sub th} and the crack growth rate da/dN was investigated experimentally for the growth of long cracks under cyclic loading for different R-values at room temperature. Additional tests were performed at T=288 C in order to investigate the role of temperature on crack growth rates. The effect of overloads in tension and compression as another factor influencing the crack growth was also studied. Measured crack growth curves were fitted using Paris and Erdogan-Ratwani law as well as the NASGRO-equation. Fracture surfaces of selected specimens for both steels

Cyclic Voltammetry of Highly Hydrophilic Ions at a Supported Liquid Membrane

Czech Academy of Sciences Publication Activity Database

Ulmeanu, S. M.; Jensen, H.; Samec, Zdeněk; Bouchard, G.; Carrupt, P. A.; Giraut, H. H.

2002-01-01

Roč. 530, 1/2 (2002), s. 10-15 ISSN 0022-0728 R&D Projects: GA AV ČR IAA4040902 Institutional research plan: CEZ:AV0Z4040901 Keywords : liquid-liquid interface * membrane * cyclic voltammetry Subject RIV: CG - Electrochemistry Impact factor: 2.027, year: 2002

[Cyclic Cushing's Syndrome - rare or rarely recognized].

Science.gov (United States)

Kiałka, Marta; Doroszewska, Katarzyna; Mrozińska, Sandra; Milewicz, Tomasz; Stochmal, Ewa

2015-01-01

Cyclic Cushing's syndrome is a type of Cushing's disease which is characterized by alternating periods of increasing and decreasing levels of cortisol in the blood. The diagnostic criteria for cyclic Cushing's syndrome are at least three periods of hypercortisolism alternating with at least two episodes of normal levels of serum cortisol concentration. The epidemiology, signs, symptoms, pathogenesis and treatment of cyclic Cushing's syndrome have been discussed.

A LabVIEW based experiment system for the efficient collection and analysis of cyclic voltametry and electrode charge capacity measurements.

Science.gov (United States)

Detlefsen, D; Hu, Z; Troyk, P R

2006-01-01

Cyclic voltametry and recording of stimulation electrode voltage excursions are two critical methods of measurement for understanding the performance of implantable electrodes. Because implanted electrodes cannot easily be replaced, it is necessary to have an a-priori understanding of an electrode's implanted performance and capabilities. In-vitro exhaustive tests are often needed to quantify an electrodes performance. Using commonly available equipment, the human labor cost to conduct this work is immense. Presented is an automated experiment system that is highly configurable that can efficiently conduct a battery of repeatable CV and stimulation recording measurements. Results of preparing 96 electrodes prior to an animal implantation are also discussed.

Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells.

Directory of Open Access Journals (Sweden)

Tiziana Angrisano

Full Text Available Bacterial lipopolysaccharide (LPS induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3, methylation (H3K4, H3K9, H3K27 and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene.

The effects of histamine and prostaglandin D2 on rat mast-cell cyclic AMP and mediator release

International Nuclear Information System (INIS)

Wescott, S.; Kaliner, M.

1981-01-01

The possibility that histamine may play a functional role in modulating mast-cell secretion, as has been suggested for basophil degranulation, has both physiologic and pharmacologic implications. Therefore the capacity of histamine to influence rat peritoneal mast-cell (RPMC) cyclic AMP levels and reversed anaphylatic degranulation as reflected in the release of 3H-serotonin (5-HT) was examined. To ascertain that RPMC were functionally responsive to exogenous hormonal stimulation, assessment of prostaglandin (PG) D2 effects on cyclic AMP and 5-HT release were determined in parallel. Although PGD2 (100 microM) increased cyclic AMP and inhibited 5-HT release in the presence of 50 microM aminophylline, histamine (up to 1000 microM) was ineffective was ineffective in both. However, 1000 microM histamine in the presence of 500 microM aminophylline was capable of transiently increasing RPMC cyclic AMP (for 15 to 30 sec) and under these conditions of suppressing 5-HT release. The receptor subtype involved in the suppressive actions of histamine appeared to be of the H-1 type as reflected in the capacity of specific H-1 agonists to reproduce the inhibition of 5-HT release, whereas neither H-2 agonists nor H-2 antagonists had any influence. Thus, under conditions in which phosphodiesterase enzymatic action is impaired, histamine in extremely high concentrations is able to modulate mast-cell secretion. However, it seems very unlikely that this action of histamine has any physiologic significance

Cyclic transformation of orbital angular momentum modes

International Nuclear Information System (INIS)

Schlederer, Florian; Krenn, Mario; Fickler, Robert; Malik, Mehul; Zeilinger, Anton

2016-01-01

The spatial modes of photons are one realization of a QuDit, a quantum system that is described in a D-dimensional Hilbert space. In order to perform quantum information tasks with QuDits, a general class of D-dimensional unitary transformations is needed. Among these, cyclic transformations are an important special case required in many high-dimensional quantum communication protocols. In this paper, we experimentally demonstrate a cyclic transformation in the high-dimensional space of photonic orbital angular momentum (OAM). Using simple linear optical components, we show a successful four-fold cyclic transformation of OAM modes. Interestingly, our experimental setup was found by a computer algorithm. In addition to the four-cyclic transformation, the algorithm also found extensions to higher-dimensional cycles in a hybrid space of OAM and polarization. Besides being useful for quantum cryptography with QuDits, cyclic transformations are key for the experimental production of high-dimensional maximally entangled Bell-states. (paper)

Changes in mechanical properties following cyclic prestressing of martensitic steel containing vanadium carbide in presence of nondiffusible hydrogen

Energy Technology Data Exchange (ETDEWEB)

Kaneko, Mao; Doshida, Tomoki [Graduate School of Science and Technology, Sophia University, Tokyo 102-8554 (Japan); Takai, Kenichi, E-mail: takai@me.sophia.ac.jp [Department of Engineering and Applied Science, Sophia University, Tokyo 102-8554 (Japan)

2016-09-30

Changes in the states of nondiffusible hydrogen and mechanical properties after cyclic prestressing in the presence of only nondiffusible hydrogen were examined for martensitic steel containing vanadium carbide. The relationship between the change in the state of nondiffusible hydrogen and mechanical properties was also investigated. The hydrogen desorption profile in the high-temperature range decreased and that in the low-temperature range increased with increasing stress amplitude during cyclic prestressing in the presence of only nondiffusible hydrogen. Thus, the application of cyclic prestressing changed the state of hydrogen from a stable to an unstable one because of vacancies and their clusters. Hydrogen embrittlement susceptibility after cyclic prestressing increased with increasing stress amplitude and number of prestressing cycles in the presence of only nondiffusible hydrogen. This relationship indicates that hydrogen embrittlement susceptibility increased with the increasing amount of hydrogen detrapped from trap sites of nondiffusible hydrogen during cyclic prestressing. These results revealed that nondiffusible hydrogen easily detrapped from vanadium carbide due to the application of cyclic prestress and probably interacted with vacancies and their clusters, thus increasing hydrogen embrittlement susceptibility. The change of nondiffusible hydrogen to diffusible hydrogen and accumulation of vacancies and their clusters during cyclic prestressing are concluded to be the dominant factors in hydrogen embrittlement after the application of cyclic prestress.

Synthesis of Cyclic Py-Im Polyamide Libraries

OpenAIRE

Li, Benjamin C.; Montgomery, David C.; Puckett, James W.; Dervan, Peter B.

2013-01-01

Cyclic Py-Im polyamides containing two GABA turn units exhibit enhanced DNA binding affinity, but extensive studies of their biological properties have been hindered due to synthetic inaccessibility. A facile modular approach toward cyclic polyamides has been developed via microwave-assisted solid-phase synthesis of hairpin amino acid oligomer intermediates followed by macrocyclization. A focused library of cyclic polyamides 1–7 targeted to the androgen response element (ARE) and the estrogen...

Rectal motility after sacral nerve stimulation for faecal incontinence

DEFF Research Database (Denmark)

Michelsen, H B; Worsøe, J; Krogh, K

2010-01-01

Sacral nerve stimulation (SNS) is effective against faecal incontinence, but the mode of action is obscure. The aim of this study was to describe the effects of SNS on fasting and postprandial rectal motility. Sixteen patients, 14 women age 33-73 (mean 58), with faecal incontinence of various...... contractions, total time with cyclic rectal contractions, the number of aborally and orally propagating contractions, the number of anal sampling reflexes or rectal wall tension during contractions. Postprandial changes in rectal tone were significantly reduced during SNS (P

Supplementary Material for: The arabidopsis cyclic nucleotide interactome

KAUST Repository

Donaldson, Lara; Meier, Stuart; Gehring, Christoph A

2016-01-01

Abstract Background Cyclic nucleotides have been shown to play important signaling roles in many physiological processes in plants including photosynthesis and defence. Despite this, little is known about cyclic nucleotide-dependent signaling mechanisms in plants since the downstream target proteins remain unknown. This is largely due to the fact that bioinformatics searches fail to identify plant homologs of protein kinases and phosphodiesterases that are the main targets of cyclic nucleotides in animals. Methods An affinity purification technique was used to identify cyclic nucleotide binding proteins in Arabidopsis thaliana. The identified proteins were subjected to a computational analysis that included a sequence, transcriptional co-expression and functional annotation analysis in order to assess their potential role in plant cyclic nucleotide signaling. Results A total of twelve cyclic nucleotide binding proteins were identified experimentally including key enzymes in the Calvin cycle and photorespiration pathway. Importantly, eight of the twelve proteins were shown to contain putative cyclic nucleotide binding domains. Moreover, the identified proteins are post-translationally modified by nitric oxide, transcriptionally co-expressed and annotated to function in hydrogen peroxide signaling and the defence response. The activity of one of these proteins, GLYGOLATE OXIDASE 1, a photorespiratory enzyme that produces hydrogen peroxide in response to Pseudomonas, was shown to be repressed by a combination of cGMP and nitric oxide treatment. Conclusions We propose that the identified proteins function together as points of cross-talk between cyclic nucleotide, nitric oxide and reactive oxygen species signaling during the defence response.

Comparative effects of sub-stimulating concentrations of non-human versus human Luteinizing Hormones (LH) or chorionic gonadotropins (CG) on adenylate cyclase activation by forskolin in MLTC cells.

Science.gov (United States)

Nguyen, Thi-Mong Diep; Filliatreau, Laura; Klett, Danièle; Combarnous, Yves

2018-05-15

We have compared various Luteinizing Hormone (LH) and Chorionic Gonadotropin (CG) preparations from non-human and human species in their ability to synergize with 10 µM forskolin (FSK) for cyclic AMP intracellular accumulation, in MLTC cells. LH from rat pituitary as well as various isoforms of pituitary ovine, bovine, porcine, equine and human LHs and equine and human CG were studied. In addition, recombinant human LH and CG were also compared with the natural human and non-human hormones. Sub-stimulating concentrations of all LHs and CGs (2-100 pM) were found to stimulate cyclic AMP accumulation in MLTC cells in the presence of an also non-stimulating FSK concentration (10 µM). Like rat LH, the most homologous available hormone for mouse MLTC cells, all non-human LHs and CG exhibit a strong potentiating effect on FSK response. The human, natural and recombinant hLH and hCG also do so but in addition, they were found to elicit a permissive effect on FSK stimulation. Indeed, when incubated alone with MLTC cells at non-stimulating concentrations (2-70 pM) hLH and hCG permit, after being removed, a dose-dependent cyclic AMP accumulation with 10 µM FSK. Our data show a clearcut difference between human LH and CG compared to their non-human counterparts on MLTC cells adenylate cyclase activity control. This points out the risk of using hCG as a reference ligand for LHR in studies using non-human cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

Science.gov (United States)

Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

2016-03-01

Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Functionalized linear and cyclic polyolefins

Energy Technology Data Exchange (ETDEWEB)

Tuba, Robert; Grubbs, Robert H.

2018-02-13

This invention relates to methods and compositions for preparing linear and cyclic polyolefins. More particularly, the invention relates to methods and compositions for preparing functionalized linear and cyclic polyolefins via olefin metathesis reactions. Polymer products produced via the olefin metathesis reactions of the invention may be utilized for a wide range of materials applications. The invention has utility in the fields of polymer and materials chemistry and manufacture.

Damage progression in silicon nitride undergoing non-conforming hybrid cyclic contact

Czech Academy of Sciences Publication Activity Database

Raga, R.; Khader, I.; Chlup, Zdeněk; Kailer, A.

2017-01-01

Roč. 105, DEC (2017), s. 97-110 ISSN 0142-1123 EU Projects: European Commission(XE) 263476 - ROLICER Institutional support: RVO:68081723 Keywords : Silicon nitride * Cyclic contact fatigue * Surface and subsurface damage Subject RIV: JL - Materials Fatigue, Friction Mechanics OBOR OECD: Audio engineering, reliability analysis Impact factor: 2.899, year: 2016

Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1.

Science.gov (United States)

Sugiyama, A; Uehara, A; Iki, K; Matsushita, K; Nakamura, R; Ogawa, T; Sugawara, S; Takada, H

2002-01-01

Black-pigmented anaerobic bacteria, such as Porphyromonas gingivalis and Prevotella intermedia, are amongst the predominant bacteria in periodontal pockets and have been implicated in periodontal diseases. To elucidate the roles of gingival keratinocytes, which are the first cells encountered by oral bacteria in periodontal diseases, human gingival keratinocytes in primary culture were stimulated with cell-surface components of P gingivalis and Pr. intermedia. A glycoprotein fraction from Pr. intermedia (PGP) clearly augmented the release of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, as determined by enzyme-linked immunosorbent assay. This PGP also induced expression of intercellular adhesion molecule-1 (ICAM-1), as determined by flow cytometry. The augmentation of mRNA expression for these molecules was also confirmed by reverse transcription PCR. In contrast, lipopolysaccharide (LPS) from Pr. intermedia and Escherichia coli was completely inactive in these assays. LPS fraction and purified fimbriae from P gingivalis exhibited weak activities. Cytokine production and ICAM-1 expression by gingival keratinocytes might cause accumulation and activation of neutrophils in the epithelium and, therefore, may be involved in the initiation and development of inflammation in periodontal tissues.

Tumor Necrosis Factor α Stimulates Osteoclast Differentiation by a Mechanism Independent of the Odf/Rankl–Rank Interaction

Science.gov (United States)

Kobayashi, Kanichiro; Takahashi, Naoyuki; Jimi, Eijiro; Udagawa, Nobuyuki; Takami, Masamichi; Kotake, Shigeru; Nakagawa, Nobuaki; Kinosaki, Masahiko; Yamaguchi, Kyoji; Shima, Nobuyuki; Yasuda, Hisataka; Morinaga, Tomonori; Higashio, Kanji; Martin, T. John; Suda, Tatsuo

2000-01-01

Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF–dependent bone marrow macrophages (M-BMMφ) appeared within 3 d. Tartrate-resistant acid phosphatase–positive osteoclasts were also formed when M-BMMφ were further cultured for 3 d with mouse tumor necrosis factor α (TNF-α) in the presence of M-CSF. Osteoclast formation induced by TNF-α was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti–RANK (ODF/RANKL receptor) antibody. Experiments using M-BMMφ prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-α. Osteoclasts induced by TNF-α formed resorption pits on dentine slices only in the presence of IL-1α. These results demonstrate that TNF-α stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL–RANK system. TNF-α together with IL-1α may play an important role in bone resorption of inflammatory bone diseases. PMID:10637272

A Randomized Case-Controlled Study of Recombinant Human Granulocyte Colony Stimulating Factor for the Treatment of Sepsis in Preterm Neutropenic Infants

OpenAIRE

Aktaş, Doğukan; Demirel, Bilge; Gürsoy, Tuğba; Ovalı, Fahri

2015-01-01

To investigate the efficacy and safety of recombinant human granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) to treat sepsis in neutropenic preterm infants. Methods: Fifty-six neutropenic preterm infants with suspected or culture-proven sepsis hospitalized in Zeynep Kamil Maternity and Children's Educational and Training Hospital, Kozyatağı/Istanbul, Turkey between January 2008 and January 2010 were enrolled. Patients were ...

Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes

Directory of Open Access Journals (Sweden)

Yan Wang

2015-01-01

Full Text Available Rheumatoid arthritis (RA is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdown of cGAS inhibited the proliferation of RA FLS. cGAS overexpression enhanced the production of proinflammatory cytokines and matrix metalloproteinases (MMPs as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. In contrast, cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. These results suggest that cGAS activates the AKT and ERK pathways to promote the inflammatory response of RA FLS, and the development of strategies targeting cGAS may have therapeutic potential for human RA.

Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes.

Science.gov (United States)

Wang, Yan; Su, Guo-Hua; Zhang, Fang; Chu, Jing-Xue; Wang, Yun-Shan

2015-01-01

Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdown of cGAS inhibited the proliferation of RA FLS. cGAS overexpression enhanced the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. In contrast, cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. These results suggest that cGAS activates the AKT and ERK pathways to promote the inflammatory response of RA FLS, and the development of strategies targeting cGAS may have therapeutic potential for human RA.

Stimulation of 2-methylisoborneol (MIB) production by actinomycetes after cyclic chlorination in drinking water distribution systems.

Science.gov (United States)

Abbaszadegan, Morteza; Yi, Min; Alum, Absar

2015-01-01

The impact of fluctuation in chlorine residual on actinomycetes and the production of 2-methylisoborneol (MIB) were studied in cast-iron and PVC model distribution systems. Actinomycetes were spiked in each system and continued operation for a 12-day non-chlorine experiment, resulting in no changes in actinomycetes and MIB concentrations. Three cyclic chlorination events were performed and chlorine residuals were maintained as follows: 1.0 mg L(-1) for 24 h, 0 mg L(-1) for 48 h, 0.5 mg L(-1) for 48 h, 0 mg L(-1) for 48 h and 2 mg L(-1) for 24 h. After each chlorination event, 2 -3 log decrease in actinomycetes was noted in both systems. However, within 48 h at 0 mg L(-1) chlorine, the actinomycetes recovered to the pre-chlorination levels. On the contrary, MIB concentration in both systems remained un-impacted after the first cycle and increased by fourfold ( 20 mg L(-1)) after the second cycle, which lasted through the third cycle despite the fact that actinomycetes numbers fluctuated 2-3 logs during this time period. For obtaining biofilm samples from field, water meters were collected from municipality drinking water distribution systems located in central Arizona. The actinomycetes concentration in asbestos cement pipe and cast iron pipe averaged 3.1 × 10(3) and 1.9 × 10(4) CFU cm(-2), respectively. The study shows that production of MIB is associated with changes in chlorine residual in the systems. This is the first report of cyclic chlorine shock as a stimulus for MIB production by actinomycetes in drinking water distribution system's ecology.

A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization

DEFF Research Database (Denmark)

Ziebe, Søren; Loft, Anne; Povlsen, Betina B

2013-01-01

To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR).......To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR)....

Regulation of rat hepatocyte function by P2Y receptors: focus on control of glycogen phosphorylase and cyclic AMP by 2-methylthioadenosine 5'-diphosphate.

Science.gov (United States)

Dixon, C Jane; Hall, John F; Webb, Tania E; Boarder, Michael R

2004-10-01

Hepatocyte function is regulated by several P2Y receptor subtypes. Here we report that 2-methylthioadenosine 5'-diphosphate (2-MeSADP), an agonist at P2Y(1), P2Y(12), and P2Y(13) receptors, potently (threshold 30 nM) stimulates glycogen phosphorylase in freshly isolated rat hepatocytes. Antagonism by N(6)-methyl 2'-deoxyadenosine 3',5'-bisphosphate (MRS 2179) confirms that this response is mediated by P2Y(1) receptors. In addition, in these cells, both 2-MeSADP and UTP inhibited glucagon-stimulated cyclic AMP accumulation. This inhibitory effect of 2-MeSADP was not reversed by the P2Y(1) antagonists, adenosine-3'-phosphate-5'-phosphate (A3P5P) or MRS 2179, both in the range 1 to 300 microM, indicating that it was not mediated by P2Y(1) receptors. This contrasts with the increase in cytosolic free Ca(2+) concentration ([Ca(2+)](c)) induced by 2-MeSADP, which has shown to be inhibited by A3P5P. Pertussis toxin abolished the inhibitory effect of both UTP and 2-MeSADP. After culture of cells for 48 h, the ability of 2-MeSADP to inhibit cyclic AMP accumulation was greatly diminished. Reverse transcriptase-polymerase chain reaction analysis revealed that during this culture period, there was a decline in the ability to detect transcripts for P2Y(12) and P2Y(13) receptors, both of which are activated by 2-MeSADP and negatively coupled to adenylyl cyclase. However, in freshly isolated cells, the P2Y(12) and P2Y(13) receptor antagonist, 2-propylthio-beta,gamma-dichloromethylene-d-ATP (AR-C67085) (10 nM to 300 microM) did not alter the ability of 2-MeSADP to inhibit glucagon-stimulated cyclic AMP accumulation. We conclude that 2-MeSADP regulates rat hepatocyte glycogen phosphorylase by acting on P2Y(1) receptors coupled to raised [Ca(2+)](c), and by inhibiting cyclic AMP levels by an unknown G(i)-coupled receptor subtype, distinct from P2Y(1), P2Y(12), or P2Y(13) receptors.

Cyclic Processing for Context Fusion

DEFF Research Database (Denmark)

Kjærgaard, Mikkel Baun

2007-01-01

Many machine-learning techniques use feedback information. However, current context fusion systems do not support this because they constrain processing to be structured as acyclic processing. This paper proposes a generalization which enables the use of cyclic processing in context fusion systems....... A solution is proposed to the inherent problem of how to avoid uncontrollable looping during cyclic processing. The solution is based on finding cycles using graph-coloring and breaking cycles using time constraints....

Türkiye Maden Sektörü İhracatına Konjonktürel Faktörlerin Etkisi(The Impact of Cyclical Factors on The Export of Mining Industry in Turkey

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Alper SÖNMEZ

2016-08-01

Full Text Available The main purpose of the study is to analyze the cyclical fluctuations experienced in the export of mining industry in Turkey for the period over 1992-2013, and evaluate the development processes of the sector’s export by analyzing the economic factors behind these fluctuations. For this purpose, by using monthly and yearly time series data related to sector’s export, the estimated trend function is calculated by performing linear and quadratic regression analyses by the method of ordinary least squares. The results revealed that the estimated export trend function is a quadratic. According to the findings, it seems that the export of the sector rises and falls irregularly, it is also seen that these fluctuations have gained the stability especially for the pre-2000 period. This situation indicates that the export of the mining sector is affected from both internal and external many political and economic factors and that somehow it has been unable to stabilize in this period. After the 2000s, due to relatively stable and successful economic management, internal cyclical fluctuations are occurred at lower level. The most important cyclical fluctuation occurred in this period (after 2000s is 2008 global financial crisis, which is an external phenomenon; in subsequent two years the export of the Turkish mining sector declined 22 percent

Ultrathin monomolecular films and robust assemblies based on cyclic catechols

Czech Academy of Sciences Publication Activity Database

Zieger, M. M.; Pop-Georgievski, Ognen; de los Santos Pereira, Andres; Verveniotis, E.; Preuss, C. M.; Zorn, M.; Reck, B.; Goldmann, A. S.; Rodriguez-Emmenegger, Cesar; Barner-Kowollik, C.

2017-01-01

Roč. 33, č. 3 (2017), s. 670-679 ISSN 0743-7463 R&D Projects: GA ČR(CZ) GJ15-09368Y Grant - others:OPPK(XE) CZ.2.16/3.1.00/21545 Program:OPPK Institutional support: RVO:61389013 Keywords : cyclic catechols * ultrathin films * macromolecules monolayers Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.833, year: 2016

Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing.

Science.gov (United States)

Crosby, Lynn M; Luellen, Charlean; Zhang, Zhihong; Tague, Larry L; Sinclair, Scott E; Waters, Christopher M

2011-10-01

After acute lung injury, repair of the alveolar epithelium occurs on a substrate undergoing cyclic mechanical deformation. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. We examined epithelial repair during cyclic stretch (CS) in a scratch-wound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caused significant intercellular gap formation compared with static cells. Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier.

Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

Energy Technology Data Exchange (ETDEWEB)

Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

1987-01-01

Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.

Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

International Nuclear Information System (INIS)

Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

1987-01-01

Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters

Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.

Science.gov (United States)

Alevizos, Michail; Karagkouni, Anna; Vasiadi, Magdalini; Sismanopoulos, Nikolaos; Makris, Michael; Kalogeromitros, Dimitrios; Theoharides, Theoharis C

2013-12-01

Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comparison Of INAA Methods (Long Conventional, Cyclic And Pseudo-Cyclic) For The Determination Of Se In Biological Samples

International Nuclear Information System (INIS)

Sarheel, A.

2004-01-01

Selenium content in serum blood, sample were received from international comparison programme (SABC) has been determined by Cyclic irradiation, pseudo-cyclic irradiation and long irradiation conventional Instrumental neutron activation analysis through the 162 keV gamma ray of the 77m Se nuclide for both cyclic and pseudo-cyclic and 264 keV gamma ray of 75 Se nuclide for conventional (long irradiation). The CINAA involve irradiation of samples for 20 s, decay for 15 s and counting for 20 s, samples recycling four times to improve the precision. The PCINAA involve irradiation of samples for 20 s, decay for 20 s and counting for 30s, samples recycling four times day by day. The Conventional (long irradiation) involve irradiation of samples for 20 hr (1 week), decay for 4 weeks and counting for 20 hr. The accuracy has been evaluated by analyzing the certified reference materials. (Author)

Cyclic Soft Groups and Their Applications on Groups

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Hacı Aktaş

2014-01-01

Full Text Available In crisp environment the notions of order of group and cyclic group are well known due to many applications. In this paper, we introduce order of the soft groups, power of the soft sets, power of the soft groups, and cyclic soft group on a group. We also investigate the relationship between cyclic soft groups and classical groups.

HOST liner cyclic facilities: Facility description

Science.gov (United States)

Schultz, D.

1982-01-01

A quartz lamp box, a quartz lamp annular rig, and a low pressure liner cyclic can rig planned for liner cyclic tests are described. Special test instrumentation includes an IR-TV camera system for measuring liner cold side temperatures, thin film thermocouples for measuring liner hot side temperatures, and laser and high temperature strain gages for obtaining local strain measurements. A plate temperature of 2,000 F was obtained in an initial test of an apparatus with three quartz lamps. Lamp life, however, appeared to be limited for the standard commercial quartz lamps available. The design of vitiated and nonvitiated preheaters required for the quartz lamp annular rig and the cyclic can test rigs is underway.

Rhodium-Catalyzed Dehydrogenative Borylation of Cyclic Alkenes

Science.gov (United States)

Kondoh, Azusa; Jamison, Timothy F.

2010-01-01

A rhodium-catalyzed dehydrogenative borylation of cyclic alkenes is described. This reaction provides direct access to cyclic 1-alkenylboronic acid pinacol esters, useful intermediates in organic synthesis. Suzuki-Miyaura cross-coupling applications are also presented. PMID:20107646

The effect of aroma stimulation during isotonic exercise on the rating of perceived exertion and blood fatigue factors of athletes with patellofemoral pain syndrome.

Science.gov (United States)

Kim, Sangsoo; Choo, JongHoo; Ju, Sungbum

2018-02-01

[Purpose] The purpose of this study is to examine the effect of aroma stimulation during isotonic exercise on the rating of perceived exertion (RPE) and the blood fatigue factors of athletes who have patellofemoral pain syndrome (PFPS). [Subjects and Methods] The research subjects were seven athletes in their twenties who suffer from PFPS. They were divided into a control group and an aroma stimulation group and performed isotonic exercises repeatedly. After exercising, the RPE and blood fatigue factors, including creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and ammonia, were measured through blood sampling. [Results] The aroma stimulus group showed significantly lower RPE than the control group immediately after exercising, which included leg presses, leg curls, bicep curls, and leg extensions. Among the blood fatigue factors, the change in LDH indicated the effect of aroma stimulation. [Conclusion] We confirmed that aroma stimulation during isotonic exercise has the positive effect of reducing the RPE and blood fatigue factors, such as blood LDH, of the athletes with PFPS.

Differential model of macroeconomic growth with endogenic cyclicity

Directory of Open Access Journals (Sweden)

Mikhail I. Geraskin

2017-09-01

Full Text Available Objective to elaborate a mathematical model of economic growth taking into account the cyclical nature of macroeconomic dynamics with the model parameters based on the Russian economy statistics. Methods economic and mathematical modeling system analysis regression factor analysis econometric time series analysis. Results the article states that under unstable economic growth in Russia forecasting of strategic prospects of the Russian economy is one of the topical directions of scientific studies. Furthermore construction of predictive models should be based on multiple factors taking into account such basic concepts as the neoKeynesian HarrodDomar model Ramsey ndash Cass ndash Koopmans model S. V. Dubovskiyrsquos concept as well as the neoclassical growth model by R. Solow. They served as the basis for developing a multifactor differential economic growth model which is a modification of the neoclassical growth model by R. Solow taking into account the laborsaving and capitalsaving forms of scientifictechnical progress and the Keynesian concept of investment. The model parameters are determined based on the dynamics of actual GDP employment fixed assets and investments in fixed assets for 19652016 in Russia on the basis of official statistics. The generalized model showed the presence of longwave fluctuations that are not detected during the individual periods modeling. The cyclical nature of macroeconomic dynamics with a period of 54 years was found which corresponds to the parameters of long waves by N. D. Kondratiev. Basing on the model the macroeconomic growth forecast was generated which shows that after 2020 the increase of scientifictechnical progress will be negative. Scientific novelty a model is proposed of the scientifictechnical progress indicator showing the growth rate of the capital productivity ratio to the saving rate a differential model of macroeconomic growth is obtained which endogenously takes cyclicity into account

Bianchi type I cyclic cosmology from Lie-algebraically deformed phase space

International Nuclear Information System (INIS)

Vakili, Babak; Khosravi, Nima

2010-01-01

We study the effects of noncommutativity, in the form of a Lie-algebraically deformed Poisson commutation relations, on the evolution of a Bianchi type I cosmological model with a positive cosmological constant. The phase space variables turn out to correspond to the scale factors of this model in x, y, and z directions. According to the conditions that the structure constants (deformation parameters) should satisfy, we argue that there are two types of noncommutative phase space with Lie-algebraic structure. The exact classical solutions in commutative and type I noncommutative cases are presented. In the framework of this type of deformed phase space, we investigate the possibility of building a Bianchi I model with cyclic scale factors in which the size of the Universe in each direction experiences an endless sequence of contractions and reexpansions. We also obtain some approximate solutions for the type II noncommutative structure by numerical methods and show that the cyclic behavior is repeated as well. These results are compared with the standard commutative case, and similarities and differences of these solutions are discussed.

Cyclic plastic response and fatigue life of duplex and superduplex stainless steel

Czech Academy of Sciences Publication Activity Database

Polák, Jaroslav

43 2005, č. 4 (2005), s. 280-289 ISSN 0023-432X R&D Projects: GA ČR(CZ) GA106/02/0584 Institutional research plan: CEZ:AV0Z20410507 Keywords : duplex steel * fatigue life * cyclic plasticity Subject RIV: JG - Metallurgy Impact factor: 0.973, year: 2005

Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls

Directory of Open Access Journals (Sweden)

Junghwan Suh

2013-12-01

Full Text Available PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH stimulation test is required to diagnose central precocious puberty (CPP, however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH, follicle-stimulating hormone (FSH, and estradiol (E2, were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group. The CPP group had advanced bone age (P<0.001, accelerated yearly growth rate (P<0.001, increased basal levels of LH (P=0.02, FSH (P<0.001, E2 (P=0.001, and insulin-like growth factor-I levels (P<0.001 compared to the non-CPP group. In contrast, body weight (P<0.001 and body mass index (P<0.001 were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.

Cyclic GMP alters Ca exchange in vascular smooth muscle

International Nuclear Information System (INIS)

Magliola, L.; Bailey, B.; Jones, A.W.

1986-01-01

Contraction and 42 K efflux from vascular smooth muscle stimulated either by norepinephrine (NE) or by K-depolarization is dependent on an increase in cytosolic Ca concentration. The purpose of this study was to determine if cyclic GMP (cGMP) inhibited these processes and if inhibition was secondary to the action of cGMP on Ca movements. Basal cGMP content of rat aorta was 1.2 fmol/mg wet wt. Sodium nitroprusside (NP) increased cGMP ∼2-fold at 1 nM and ∼750-fold at 1 μM with no effect on cAMP levels. A 5 min pretreatment with NP (1 μM) completely prevented tension development induced by 3 μM NE. The same concentration of NP also inhibited NE-stimulated 42 K and 45 Ca efflux > 90 and > 80%, respectively. Removal of NP in the continued presence of NE (3 μM) caused recovery of the 42 K efflux response to ∼75% of control with a half-time of ∼2.5 min. NP (1 μM) also caused a rapid relaxation of aorta contracted with 3 μM NE and a loss of the 42 K efflux response with half-times of 2-3 min. In contrast, 100 μM NP produced only a 50% inhibition of contraction induced by high K (55 mM). Also, NP (1 μM) inhibited K-stimulated 42 K efflux only ∼25%. These results demonstrate both a concentration- and a time-dependent relationship between increases in cGMP induced by NP and decreases in NE-stimulated contraction, 42 K and 45 Ca effluxes. They also indicate that the sensitivity of NE-induced contraction and 42 K efflux to NP is greater than that induced by high K. These studies suggest that cGMP modulates the control sites for Ca exchange in the plasma membrane and sarcoplasmic reticulum

Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

Science.gov (United States)

Abdo, Shaaban; Shi, Yixuan; Otoukesh, Abouzar; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao Ling; Chan, John S D

2014-10-01

This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

3' : 5'-Cyclic AMP-dependent 3'

NARCIS (Netherlands)

Mato, José M.; Krens, Frans A.; Haastert, Peter J.M. van; Konijn, Theo M.

1977-01-01

Suspensions of 3':5'-cyclic AMP (cAMP)-sensitive cells of Dictyostelium discoideum responded to a cAMP pulse with increased 3':5'-cyclic GMP (cGMP) levels. Under the assay conditions used (2 × 10^8 cells per ml in 10 mM phosphate buffer, pH 6.0) cAMP (5 × 10-8 M final concentration) increased cGMP

Timing of granulocyte-colony stimulating factor treatment after acute myocardial infarction and recovery of left ventricular function: results from the STEMMI trial

DEFF Research Database (Denmark)

Overgaard, Mikkel; Ripa, Rasmus Sejersten; Wang, Yongzhong

2010-01-01

Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial.......Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial....

Recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) treatment of clozapine-induced agranulocytosis

DEFF Research Database (Denmark)

Nielsen, H

1993-01-01

After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease...

Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA.

Science.gov (United States)

Kato, Kazuki; Omura, Hiroki; Ishitani, Ryuichiro; Nureki, Osamu

2017-06-20

The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclic GMP-AMP (2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Numerous crystal structures of the components of this cGAS/STING signaling axis have been reported and these clarify the structural basis for their signal transduction mechanisms. In this review, we summarize recent progress made in the structural dissection of this signaling pathway and indicate possible directions of forthcoming research.

A comparison of two reciprocating instruments using bending stress and cyclic fatigue tests

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Pantaleo SCELZA

2015-01-01

Full Text Available The aim of this study was to comparatively evaluate the bending resistance at 45º, the static and dynamic cyclic fatigue life, and the fracture type of the WaveOne (Dentsply Maillefer, Ballaigues, Switzerland 25-08 and Reciproc (VDW, Munich, Germany 25-08 instruments. A total of 60 nickel-titanium (NiTi instruments (30 Reciproc and 30 WaveOne from three different lots, each of which was 25 mm in length, were tested. The bending resistance was evaluated through the results of a cantilever-bending test conducted using a universal testing machine. Static and dynamic cyclic fatigue testing was conducted using a custom-made device. For the static and dynamic tests, a cast Ni-Cr-Mo-Ti alloy metal block with an artificial canal measuring 1.77 mm in diameter and 20.00 mm in total length was used. A scanning electron microscope was used to determine the type of fracture. Statistical analyses were performed on the results. The WaveOne instrument was less flexible than the Reciproc (p < 0.05. The Reciproc instrument showed better resistance in the static and dynamic cyclic fatigue tests (p < 0.05. The transverse cross-section and geometry of the instruments were important factors in their resistance to bending and cyclic fracture. Both of the instruments showed ductile-type fracture characteristics. It can be concluded that the Reciproc 25-08 instrument was more resistant to static and dynamic cyclic fatigue than the WaveOne 25-08 instrument, while the WaveOne 25-08 instrument was less flexible. Bending and resistance to cyclic fracture were influenced by the instruments’ geometries and transverse cross-sections. Both of the instruments showed ductile-type fracture characteristics.

Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis

DEFF Research Database (Denmark)

Pedersen, Line Merete Blak; Jacobsen, Søren; Garred, Peter

2007-01-01

To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs)....

Design of Recombinant Stem Cell Factor macrophage Colony Stimulating Factor Fusion Proteins and their Biological Activity In Vitro

Science.gov (United States)

Chen, Tao; Yang, Jie; Wang, Yuelang; Zhan, Chenyang; Zang, Yuhui; Qin, Junchuan

2005-05-01

Stem cell factor (SCF) and macrophage colony stimulating factor (M-CSF) can act in synergistic way to promote the growth of mononuclear phagocytes. SCF-M-CSF fusion proteins were designed on the computer using the Homology and Biopolymer modules of the software packages InsightII. Several existing crystal structures were used as templates to generate models of the complexes of receptor with fusion protein. The structure rationality of the fusion protein incorporated a series of flexible linker peptide was analyzed on InsightII system. Then, a suitable peptide GGGGSGGGGSGG was chosen for the fusion protein. Two recombinant SCF-M-CSF fusion proteins were generated by construction of a plasmid in which the coding regions of human SCF (1-165aa) and M-CSF (1-149aa) cDNA were connected by this linker peptide coding sequence followed by subsequent expression in insect cell. The results of Western blot and activity analysis showed that these two recombinant fusion proteins existed as a dimer with a molecular weight of 84 KD under non-reducing conditions and a monomer of 42 KD at reducing condition. The results of cell proliferation assays showed that each fusion protein induced a dose-dependent proliferative response. At equimolar concentration, SCF/M-CSF was about 20 times more potent than the standard monomeric SCF in stimulating TF-1 cell line growth, while M-CSF/SCF was 10 times of monomeric SCF. No activity difference of M-CSF/SCF or SCF/M-CSF to M-CSF (at same molar) was found in stimulating the HL-60 cell linear growth. The synergistic effect of SCF and M-CSF moieties in the fusion proteins was demonstrated by the result of clonogenic assay performed with human bone mononuclear, in which both SCF/M-CSF and M-CSF/SCF induced much higher number of CFU-M than equimolar amount of SCF or M-CSF or that of two cytokines mixture.

Nearly Cyclic Pursuit and its Hierarchical variant for Multi-agent Systems

DEFF Research Database (Denmark)

Iqbal, Muhammad; Leth, John-Josef; Ngo, Trung Dung

2015-01-01

The rendezvous problem for multiple agents under nearly cyclic pursuit and hierarchical nearly cyclic pursuit is discussed in this paper. The control law designed under nearly cyclic pursuit strategy enables the agents to converge at a point dictated by a beacon. A hierarchical version of the nea......The rendezvous problem for multiple agents under nearly cyclic pursuit and hierarchical nearly cyclic pursuit is discussed in this paper. The control law designed under nearly cyclic pursuit strategy enables the agents to converge at a point dictated by a beacon. A hierarchical version...

Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture.

Science.gov (United States)

Krieger, N S; Stappenbeck, T S; Stern, P H

1987-01-01

The cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones. Threshold doses were 0.1 microM in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations below 0.1 mM did not affect calvarial cyclic AMP. 0.5 microM indomethacin inhibited milrinone effects in calvaria but usually not in limb bones. 3 nM calcitonin inhibited milrinone-stimulated resorption and there was no escape from this inhibition. Structural homology between milrinone and thyroxine has been reported. We find similarities between milrinone and thyroxine actions on bone, because prostaglandin production was crucial for the effects of both agents in calvaria but not in limb bones, and neither agent exhibited escape from calcitonin inhibition. PMID:3027124

Performance of Geosynthetic-Reinforced Soils Under Static and Cyclic Loading

Directory of Open Access Journals (Sweden)

M. Touahmia

2017-04-01

Full Text Available This paper investigates and discusses the composite behavior of geosynthetic reinforced soil mass. It presents the results of a series of large-scale laboratory tests supported by analytical methods to examine the performance of geogrid reinforcement subjected to static and cyclic pullout loading. The testing equipment and procedures used for this investigation are outlined. The results show that geosynthetic reinforcement can mobilize great resistance to static pulling load under high confining pressures. The reinforcement exhibits gradual deformation under cyclic loading showing no sign of imminent pullout failure for all levels of applied loads. In general, the results demonstrate that geosynthetic can be used in situations where loads are non-static, although care will be required in ensuring that appropriate factors of safety are applied to control the resulting deformation. A simplified analytical model for calculating the pulling capacity of geosynthetic reinforcement is proposed.

Proteomic Profiling of Mesenchymal Stem Cell Responses to Mechanical Strain and TGF-B1

Energy Technology Data Exchange (ETDEWEB)

Kurpinski, Kyle; Chu, Julia; Wang, Daojing; Li, Song

2009-10-12

Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression level, BGH3 was induced by TGF-{beta}1, but calponin 3 was not significantly regulated by mechanical strain or TGF-{beta}1, which was in contrast to the synergistic up-regulation of calponin 1 gene expression by cyclic strain and TGF-{beta}1. Further experiments with cycloheximide treatment suggested that the up-regulation of calponin 3 by cyclic strain was at post-transcriptional level. The results in this study suggest that both mechanical stimulation and TGF-{beta}1 signaling play unique and important roles in the regulation of MSCs at both transcriptional and post-transcriptional levels, and that a precise combination of microenvironmental cues may promote MSC differentiation.

CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

NARCIS (Netherlands)

Doorduijn, JK; van der Holt, B; van Imhoff, GW; van der Hem, KG; Kramer, MHH; van Oers, MHJ; Ossenkoppele, GJ; Verdonck, LF; Verhoef, GEG; Steijaert, MMC; Buijt, I.; Uyl-de Groot, CA; van Agthoven, M; Mulder, AH; Sonneveld, P; Schaafsma, M.

2003-01-01

Purpose : To investigate whether the relative close-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

NARCIS (Netherlands)

Doorduijn, J. K.; van der Holt, B.; van Imhoff, G. W.; van der Hem, K. G.; Kramer, M. H. H.; van Oers, M. H. J.; Ossenkoppele, G. J.; Schaafsma, M. R.; Verdonck, L. F.; Verhoef, G. E. G.; Steijaert, M. M. C.; Buijt, I.; Uyl-de Groot, C. A.; van Agthoven, M.; Mulder, A. H.; Sonneveld, P.

2003-01-01

PURPOSE: To investigate whether the relative dose-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

Cyclic diguanylic acid and cellulose synthesis in Agrobacterium tumefaciens

International Nuclear Information System (INIS)

Amikam, D.; Benziman, M.

1989-01-01

The occurrence of the novel regulatory nucleotide bis(3',5')-cyclic diguanylic acid (c-di-GMP) and its relation to cellulose biogenesis in the plant pathogen Agrobacterium tumefaciens was studied. c-di-GMP was detected in acid extracts of 32 P-labeled cells grown in various media, and an enzyme responsible for its formation from GTP was found to be present in cell-free preparations. Cellulose synthesis in vivo was quantitatively assessed with [ 14 C]glucose as a tracer. The organism produced cellulose during growth in the absence of plant cells, and this capacity was retained in resting cells. Synthesis of a cellulosic product from UDP-glucose in vitro with membrane preparations was markedly stimulated by c-di-GMP and its precursor GTP and was further enhanced by Ca2+. The calcium effect was attributed to inhibition of a c-di-GMP-degrading enzyme shown to be present in the cellulose synthase-containing membranes

Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line

International Nuclear Information System (INIS)

Hirata, Y.; Uchihashi, M.; Nakashima, H.; Fujita, T.; Matsukura, S.; Matsui, K.

1984-01-01

Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E 2 , a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125 I-labelled EGF: the apparent dissociation constant was approximately 4-10 x 10 -10 M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125 I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE 2 into medium, while no significant amount of PGE 2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE 2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE 1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGFsub(2α) PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 of G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE 2 -mediated process in human osseous tissues. (author)

Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription.

Science.gov (United States)

Stavreva, Diana A; Wiench, Malgorzata; John, Sam; Conway-Campbell, Becky L; McKenna, Mervyn A; Pooley, John R; Johnson, Thomas A; Voss, Ty C; Lightman, Stafford L; Hager, Gordon L

2009-09-01

Studies on glucocorticoid receptor (GR) action typically assess gene responses by long-term stimulation with synthetic hormones. As corticosteroids are released from adrenal glands in a circadian and high-frequency (ultradian) mode, such treatments may not provide an accurate assessment of physiological hormone action. Here we demonstrate that ultradian hormone stimulation induces cyclic GR-mediated transcriptional regulation, or gene pulsing, both in cultured cells and in animal models. Equilibrium receptor-occupancy of regulatory elements precisely tracks the ligand pulses. Nascent RNA transcripts from GR-regulated genes are released in distinct quanta, demonstrating a profound difference between the transcriptional programs induced by ultradian and constant stimulation. Gene pulsing is driven by rapid GR exchange with response elements and by GR recycling through the chaperone machinery, which promotes GR activation and reactivation in response to the ultradian hormone release, thus coupling promoter activity to the naturally occurring fluctuations in hormone levels. The GR signalling pathway has been optimized for a prompt and timely response to fluctuations in hormone levels, indicating that biologically accurate regulation of gene targets by GR requires an ultradian mode of hormone stimulation.

Effects of cyclic stretch on proliferation of mesenchymal stem cells and their differentiation to smooth muscle cells

International Nuclear Information System (INIS)

Ghazanfari, Samane; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali

2009-01-01

Bone marrow mesenchymal stem cells (MSCs) are capable of differentiating into a variety of cell types such as vascular smooth muscle cells (SMCs). In this study, we investigated influence of cyclic stretch on proliferation of hMSCs for different loading conditions, alignment of actin filaments, and consequent differentiation to SMCs. Isolated cells from bone marrow were exposed to cyclic stretch utilizing a customized device. Cell proliferation was examined by MTT assay, alignment of actin fibers by a designed image processing code, and cell differentiation by fluorescence staining. Results indicated promoted proliferation of hMSCs by cyclic strain, enhanced by elevated strain amplitude and number of cycles. Such loading regulated smooth muscle α-actin, and reoriented actin fibers. Cyclic stretch led to differentiation of hMSCs to SMCs without addition of growth factor. It was concluded that applying appropriate loading treatment on hMSCs could enhance proliferation capability, and produce functional SMCs for engineered tissues.

[Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

Science.gov (United States)

Ruszczak, Z; Ciborska, L; Kaszuba, A

1988-12-01

The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

Fast-scan cyclic voltammetry (FSCV) detection of endogenous octopamine in Drosophila melanogaster ventral nerve cord

Science.gov (United States)

Pyakurel, Poojan; Privman, Eve; Venton, B. Jill

2016-01-01

Octopamine is an endogenous biogenic amine neurotransmitter, neurohormone, and neuromodulator in invertebrates, and has functional analogy with norepinephrine in vertebrates. Fast-scan cyclic voltammetry (FSCV) can detect rapid changes in neurotransmitters, but FSCV has not been optimized for octopamine detection in situ. The goal of this study was to characterize octopamine release in the ventral nerve cord of Drosophila larvae for the first time. An FSCV waveform was optimized so that the potential for octopamine oxidation would not be near the switching potential where interferences can occur. Endogenous octopamine release was stimulated by genetically inserting either the ATP sensitive channel, P2X2, or the red-light sensitive channelrhodopsin, CsChrimson, into cells expressing tyrosine decarboxylase (TDC), an octopamine synthesis enzyme. To ensure that release is due to octopamine and not the precursor tyramine, the octopamine synthesis inhibitor disulfiram was applied, and the signal decreased by 80%. Stimulated release was vesicular and a 2 s continuous light stimulation of CsChrimson evoked 0.22 ± 0.03 μM of octopamine release in the larval VNC. Repeated stimulations were stable with 2 or 5 minutes interstimulation times. With pulsed stimulations, the release was dependent on the frequency of applied light pulse. An octopamine transporter has not been identified, and blockers of the dopamine transporter and serotonin transporter had no significant effect on the clearance time of octopamine, suggesting they do not take up octopamine. This study shows that octopamine can be monitored in Drosophila, facilitating future studies of how octopamine release functions in the insect brain. PMID:27326831

Macromolecular Networks Containing Fluorinated Cyclic Moieties

Science.gov (United States)

2015-12-12

Briefing Charts 3. DATES COVERED (From - To) 17 Nov 2015 – 12 Dec 2015 4. TITLE AND SUBTITLE Macromolecular Networks Containing Fluorinated Cyclic... FLUORINATED CYCLIC MOIETIES 12 December 2015 Andrew J. Guenthner,1 Scott T. Iacono,2 Cynthia A. Corley,2 Christopher M. Sahagun,3 Kevin R. Lamison,4...Reinforcements Good Flame, Smoke, & Toxicity Characteristics Low Water Uptake with Near Zero Coefficient of Hygroscopic Expansion ∆ DISTRIBUTION A

SP-transcription factors are involved in basal MVP promoter activity and its stimulation by HDAC inhibitors.

Science.gov (United States)

Steiner, Elisabeth; Holzmann, Klaus; Pirker, Christine; Elbling, Leonilla; Micksche, Michael; Berger, Walter

2004-04-23

The major vault protein (MVP) has been implicated in multidrug resistance, cellular transport, and malignant transformation. In this study we aimed to identify crucial MVP promoter elements that regulate MVP expression. By mutation as well as deletion analysis a conserved proximal GC-box element was demonstrated to be essential for basal human MVP promoter transactivation. Binding of Sp-family transcription factors but not AP2 to this element in vitro and in vivo was shown by EMSA and ChIP assays, respectively. Inhibition of GC-box binding by a dominant-negative Sp1-variant and by mithramycin A distinctly attenuated MVP promoter activity. In Sp-null Drosophila cells, the silent human MVP promoter was transactivated by several human Sp-family members. In human cells the MVP promoter was potently stimulated by the histone deacetylase (HDAC) inhibitors butyrate (NaB) and trichostatin A (TSA), resulting in enhanced MVP expression. This stimulation was substantially decreased by mutation of the single GC-box and by application of mithramycin A. Treatment with HDAC inhibitors led to a distinct decrease of Sp1 but increase of Sp3 binding in vivo to the respective promoter sequence as demonstrated by ChIP assays. Summarising, this study identifies variations in Sp-transcription factor binding to a single proximal GC-box element as critical for basal MVP promoter activation and its stimulation by HDAC inhibitors.

Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

Science.gov (United States)

Le Billan, Florian; Amazit, Larbi; Bleakley, Kevin; Xue, Qiong-Yao; Pussard, Eric; Lhadj, Christophe; Kolkhof, Peter; Viengchareun, Say; Fagart, Jérôme; Lombès, Marc

2018-05-07

Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbinding of their corresponding ligands, MR being activated by both aldosterone and cortisol and GR essentially activated by cortisol. Their coexpression and ability to bind similar DNA motifs highlight the need to investigate their respective contributions to overall corticosteroid signaling. Here, we decipher the transcriptional regulatory mechanisms that underlie selective effects of MRs and GRs on shared genomic targets in a human renal cellular model. Kinetic, serial, and sequential chromatin immunoprecipitation approaches were performed on the period circadian protein 1 ( PER1) target gene, providing evidence that both receptors dynamically and cyclically interact at the same target promoter in a specific and distinct transcriptional signature. During this process, both receptors regulate PER1 gene by binding as homo- or heterodimers to the same promoter region. Our results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.-Le Billan, F., Amazit, L., Bleakley, K., Xue, Q.-Y., Pussard, E., Lhadj, C., Kolkhof, P., Viengchareun, S., Fagart, J., Lombès, M. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

Caffeine, cyclic AMP and postreplication repair of mammalian DNA

International Nuclear Information System (INIS)

Ehmann, U.K.

1976-01-01

The methylxanthines, caffeine and theophylline, inhibit postreplication repair of DNA in mammalian cells. Because they also inhibit cyclic AMP phosphodiesterase, it was thought that there might be some connection between concentrations of cyclic AMP and postreplication repair. This possibility was tested by performing DNA sedimentation experiments with a cyclic AMP-resistant mouse lymphoma cell mutant and its wild-type counterpart. The results show that there is no connection between cellular cyclic AMP concentrations and the rate of postreplication repair. Therefore, it is more likely that caffeine and theophylline inhibit postreplication repair by some other means, such as by binding to DNA

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis

OpenAIRE

England, Timothy J.; Sprigg, Nikola; Alasheev, Andrey M.; Belkin, Andrey A.; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M.

2016-01-01

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and typ...

Study of Essence of Managing Changes in Ensuring Cyclic Development of Enterprises

Directory of Open Access Journals (Sweden)

Hrynyova Valentyna M.

2013-12-01

Full Text Available The article conducts the study of essence of the change notion at stages of the life cycle of an enterprise. It justifies a necessity of study of cyclic development of enterprises within the concept of managing changes. It shows interconnection of such notions as functioning, development, flexibility and adaptability of an enterprise. It generalises and shows the essence of scientific studies of cyclic development of an enterprise. In the result of the study it reveals that evolution of concepts of managing changes and life cycle have a complex and ambiguous history. Each stage is connected with certain political, social and economic factors, which should be considered not only in the context of the international market, but, first of all, within experience of the national economy. This has to do with relatively small independent experience of the Ukrainian economy, which makes it difficult to make decisions on the basis of the organisational memory of an enterprise. The said factors make for a deeper study of theoretical and practical approaches to the study of changes at the stages of enterprise development.

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma.

Science.gov (United States)

Meler, Erika N; Scott-Moncrieff, J Catharine; Peter, Augustine T; Bennett, Sara; Ramos-Vara, Jose; Salisbury, S Kathleen; Naughton, James F

2011-06-01

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Granulocyte macrophage colony stimulating factor (GM-CSF biological actions on human dermal fibroblasts

Directory of Open Access Journals (Sweden)

S Montagnani

2009-12-01

Full Text Available Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GMCSFR on human normal skin fibroblasts from healthy subjects (NFPC and on a human normal fibroblast cell line (NHDF and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GMCSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such “differentiation” is an important event induced by such cytokine.

Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus.

Science.gov (United States)

An, Jie; Durcan, Laura; Karr, Reynold M; Briggs, Tracy A; Rice, Gillian I; Teal, Thomas H; Woodward, Joshua J; Elkon, Keith B

2017-04-01

Type I interferon (IFN) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and interferonopathies such as Aicardi-Goutières syndrome. A recently discovered DNA-activated type I IFN pathway, cyclic GMP-AMP synthase (cGAS), has been linked to Aicardi-Goutières syndrome and mouse models of lupus. The aim of this study was to determine whether the cGAS pathway contributes to type I IFN production in patients with SLE. SLE disease activity was measured by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index. Expression of messenger RNA for cGAS and IFN-stimulated genes (ISGs) was determined by quantitative polymerase chain reaction analysis. Cyclic GMP-AMP (cGAMP) levels were examined by multiple reaction monitoring with ultra-performance liquid chromatography tandem mass spectrometry. Expression of cGAS in peripheral blood mononuclear cells (PBMCs) was significantly higher in SLE patients than in normal controls (n = 51 and n = 20 respectively; P < 0.01). There was a positive correlation between cGAS expression and the IFN score (P < 0.001). The expression of cGAS in PBMCs showed a dose response to type I IFN stimulation in vitro, consistent with it being an ISG. Targeted measurement of cGAMP by tandem mass spectrometry detected cGAMP in 15% of the SLE patients (7 of 48) but none of the normal (0 of 19) or rheumatoid arthritis (0 of 22) controls. Disease activity was higher in SLE patients with cGAMP versus those without cGAMP. Increased cGAS expression and cGAMP in a proportion of SLE patients indicates that the cGAS pathway should be considered as a contributor to type I IFN production. Whereas higher cGAS expression may be a consequence of exposure to type I IFN, detection of cGAMP in patients with increased disease activity indicates potential involvement of this pathway in disease expression. © 2016, American College of Rheumatology.

The effect of cyclic and dynamic loads on carbon steel pipe

International Nuclear Information System (INIS)

Rudland, D.L.; Scott, P.M.; Wilkowski, G.M.

1996-02-01

This report presents the results of four 152-mm (6-inch) diameter, unpressurized, circumferential through-wall-cracked, dynamic pipe experiments fabricated from STS410 carbon steel pipe manufactured in Japan. For three of these experiments, the through-wall crack was in the base metal. The displacement histories applied to these experiments were a quasi-static monotonic, dynamic monotonic, and dynamic, cyclic (R = -1) history. The through-wall crack for the third experiment was in a tungsten-inert-gas weld, fabricated in Japan, joining two lengths of STS410 pipe. The displacement history for this experiment was the same history applied to the dynamic, cyclic base metal experiment. The test temperature for each experiment was 300 C (572 F). The objective of these experiments was to compare a Japanese carbon steel pipe material with US pipe material, to ascertain whether this Japanese steel was as sensitive to dynamic and cyclic effects as US carbon steel pipe. In support of these pipe experiments, quasi-static and dynamic, tensile and fracture toughness tests were conducted. An analysis effort was performed that involved comparing experimental crack initiation and maximum moments with predictions based on available fracture prediction models, and calculating J-R curves for the pipe experiments using the η-factor method

A modelling approach for exploring muscle dynamics during cyclic contractions.

Directory of Open Access Journals (Sweden)

Stephanie A Ross

2018-04-01

Full Text Available Hill-type muscle models are widely used within the field of biomechanics to predict and understand muscle behaviour, and are often essential where muscle forces cannot be directly measured. However, these models have limited accuracy, particularly during cyclic contractions at the submaximal levels of activation that typically occur during locomotion. To address this issue, recent studies have incorporated effects into Hill-type models that are oftentimes neglected, such as size-dependent, history-dependent, and activation-dependent effects. However, the contribution of these effects on muscle performance has yet to be evaluated under common contractile conditions that reflect the range of activations, strains, and strain rates that occur in vivo. The purpose of this study was to develop a modelling framework to evaluate modifications to Hill-type muscle models when they contract in cyclic loops that are typical of locomotor muscle function. Here we present a modelling framework composed of a damped harmonic oscillator in series with a Hill-type muscle actuator that consists of a contractile element and parallel elastic element. The intrinsic force-length and force-velocity properties are described using Bézier curves where we present a system to relate physiological parameters to the control points for these curves. The muscle-oscillator system can be geometrically scaled while preserving dynamic and kinematic similarity to investigate the muscle size effects while controlling for the dynamics of the harmonic oscillator. The model is driven by time-varying muscle activations that cause the muscle to cyclically contract and drive the dynamics of the harmonic oscillator. Thus, this framework provides a platform to test current and future Hill-type model formulations and explore factors affecting muscle performance in muscles of different sizes under a range of cyclic contractile conditions.

Nature of a solar cyclicity

International Nuclear Information System (INIS)

Romanchuk, P.R.

1981-01-01

The paper contains a critical review of works on studying a cyclic character of solar activity. An introduction of cyclic curves with a frequency spectrum is established to be insolvent. The Wolf, Newcomb and Waldmeier approach seems to be useful. Some evidence is given in favour of the author's conception of solar activity ciclicity of a tide nature. It is accounted for a continuous double and single effect of planets, a resonant character of this effect due to which a 10-year period of Jupiter and Saturn is transformed into an 11-year cycle of activity [ru

Safety Discrete Event Models for Holonic Cyclic Manufacturing Systems

Science.gov (United States)

Ciufudean, Calin; Filote, Constantin

In this paper the expression “holonic cyclic manufacturing systems” refers to complex assembly/disassembly systems or fork/join systems, kanban systems, and in general, to any discrete event system that transforms raw material and/or components into products. Such a system is said to be cyclic if it provides the same sequence of products indefinitely. This paper considers the scheduling of holonic cyclic manufacturing systems and describes a new approach using Petri nets formalism. We propose an approach to frame the optimum schedule of holonic cyclic manufacturing systems in order to maximize the throughput while minimize the work in process. We also propose an algorithm to verify the optimum schedule.

Regulation of phospholipid synthesis in Mycobacterium smegmatis by cyclic adenosine monophosphate

International Nuclear Information System (INIS)

Sareen, Monica; Kaur, Harpinder; Khuller, G.K.

1993-01-01

Forskolin, an adenylate cyclase activator and a cyclic AMP analogue, dibutyryl cyclic AMP have been used to examine the relationship between intracellular levels of cyclic AMP and lipid synthesis in Mycobacterium smegmatis. Total phospholipid content was found to be increased in forskolin grown cells as a result of increased cyclic AMP levels caused by activation of adenylate cyclase. Increased phospholipid content was supported by increased [ 14 C]acetate incorporation as well as increased activity of glycerol-3-phosphate acyltransferase. Pretreatment of cells with dibutyryl cyclic AMP had similar effects on lipid synthesis. Taking all these observations together it is suggested that lipid synthesis is being controlled by cyclic AMP in mycobacteria. (author). 14 refs., 4 tabs

The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

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Chao-Huei Yang

2016-01-01

Full Text Available In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05. Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05 and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2, Akt, and nuclear factor (NF-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

β-Carotene as a factor in the reconstitution of cyclic phospho rylation in damaged chloroplast membranes

Directory of Open Access Journals (Sweden)

Anna Tukendorf

2014-01-01

Full Text Available Phenazine methosulphate mediated cyclic phosphorylation suppressed by heptane extraction or galactolipase treatment of spinach chloroplasts is restored by β -carotene, in 100% and 50%, respectively. Xanthophylls are not able to reconstitute this reaction. β-Carotene replaces galactolipids in reactivation of galactolipase treated chloroplasts, indicating a nonspecific effect of lipids in photosystem I dependent reactions.

Cyclic deformation of NiTi shape memory alloys

International Nuclear Information System (INIS)

Liu Yong; Van Humbeeck, J.; Xie Zeliang

1999-01-01

Recently, there is an increasing interest in applying the high damping capacity of shape memory alloys (SMAs). The purpose is to explore the feasibility of those materials for the protection of buildings and other civil constructions as a result of earthquake damages. So far, few experimental results have been reported concerning the mechanical cyclic behaviour of SMAs in their martensitic state (ferroelastic). In the present work, the experimental results on the mechanical behaviour of martensitic NiTi SMAs under tension-compression cyclic deformation up to strains of ±4% are summarized with major attention to the damping capacity, characteristic stresses and strains as a function of deformation cycles. Effect of strain rate, strain amplitude and annealing condition on the martensite damping is summarized. Explanation of the cyclic hardening and cyclic softening phenomenon is proposed based on TEM observations. (orig.)

Cyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: enzyme and substrate characterization and functional role

Czech Academy of Sciences Publication Activity Database

Dobrová, Zuzana; Sardanelli, A. M.; Speranza, F.; Scacco, S.; Signorile, A.; Lorusso, V.; Papa, S.

2001-01-01

Roč. 40, - (2001), s. 13941-13947 ISSN 0006-2960 Institutional research plan: CEZ:AV0Z5020903 Keywords : cAMP * cyclic adenosine monophosphate Subject RIV: CE - Biochemistry Impact factor: 4.114, year: 2001

Platelet-derived growth factor (PDGF) stimulates glycogen synthase activity in 3T3 cells

International Nuclear Information System (INIS)

Chan, C.P.; Bowen-Pope, D.F.; Ross, R.; Krebs, E.G.

1986-01-01

Hormonal regulation of glycogen synthase, an enzyme that can be phosphorylated on multiple sites, is often associated with changes in its phosphorylation state. Enzyme activation is conventionally monitored by determining the synthase activity ratio [(activity in the absence of glucose 6-P)/(activity in the presence of glucose 6-P)]. Insulin causes an activation of glycogen synthase with a concomitant decrease in its phosphate content. In a previous report, the authors showed that epidermal growth factor (EGF) increases the glycogen synthase activity ratio in Swiss 3T3 cells. The time and dose-dependency of this response was similar to that of insulin. Their recent results indicate that PDGF also stimulates glycogen synthase activity. Enzyme activation was maximal after 30 min. of incubation with PDGF; the time course observed was very similar to that with insulin and EGF. At 1 ng/ml (0.03nM), PDGF caused a maximal stimulation of 4-fold in synthase activity ratio. Half-maximal stimulation was observed at 0.2 ng/ml (6 pM). The time course of changes in enzyme activity ratio closely followed that of 125 I-PDGF binding. The authors data suggest that PDGF, as well as EFG and insulin, may be important in regulating glycogen synthesis through phosphorylation/dephosphorylation mechanisms

Laterally cyclic loading of monopile in dense sand

DEFF Research Database (Denmark)

Klinkvort, Rasmus Tofte; Hededal, Ole; Svensson, M.

2011-01-01

In order to investigate the response from laterally cyclic loading of monopiles a large centrifuge tests series is ongoing at the Technical University of Denmark (DTU). This paper will present some of the tests carried out with a focus on the influence of accumulation of rotation when changing...... the loading conditions. In these tests the load conditions are controlled by two load characteristics, one controlling the level of the cyclic loading and one controlling the characteristic of the cyclic loading. The centrifuge tests were performed in dense dry sand on a pile with prototype dimensions...

Granulocyte-macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2.

Science.gov (United States)

Aoki, Manabu; Yamaguchi, Rui; Yamamoto, Takatoshi; Ishimaru, Yasuji; Ono, Tomomichi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

2015-04-01

Chronic inflammation is often linked to the presence of type 2-polarized macrophages, which are induced by the T helper type 2 cytokines interleukin-4 and interleukin-13 (IL-13). IL-13 is a key mediator of tissue fibrosis caused by T helper type 2-based inflammation. Human neutrophil elastase (HNE) plays a pivotal role in the pathogenesis of pulmonary fibrosis. This study investigated the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on IL-13 expression by macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. Expression of IL-13 mRNA and protein by GM-CSF-dependent macrophages was investigated after stimulation with HNE, using the polymerase chain reaction and enzyme-linked immunosorbent assay. GM-CSF had a priming effect on IL-13 mRNA and protein expression by macrophages stimulated with HNE, while this effect was not observed for various other cytokines. GM-CSF-dependent macrophages showed a significant increase in the expression of protease activated receptor-2 (PAR-2) mRNA and protein. The response of IL-13 mRNA to HNE was significantly decreased by pretreatment with alpha1-antitrypsin, a PAR-2 antibody (SAM11), or a PAR-2 antagonist (ENMD-1068). These findings suggest that stimulation with HNE can induce IL-13 production by macrophages, especially GM-CSF-dependent macrophages. Accordingly, neutrophil elastase may have a key role in fibrosis associated with chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Cyclic cellular automata in 3D

International Nuclear Information System (INIS)

Reiter, Clifford A.

2011-01-01

Highlights: → We explore the self-organization of cyclic cellular automata in 3D. → Von Neumann, Moore and two types of intermediate neighborhoods are investigated. → Random neighborhoods self organize through phases into complex nested structures. → Demons are seen to have many alternatives in 3D. - Abstract: Cyclic cellular automata in two dimensions have long been intriguing because they self organize into spirals and that behavior can be analyzed. The form for the patterns that develop is highly dependent upon the form of the neighborhood. We extend this work to three dimensional cyclic cellular automata and observe self organization dependent upon the neighborhood type. This includes neighborhood types intermediate between Von Neumann and Moore neighborhoods. We also observe that the patterns include nested shells with the appropriate forms but that the nesting is far more complex than the spirals that occur in two dimensions.

Biomimetic fetal rotation bioreactor for engineering bone tissues-Effect of cyclic strains on upregulation of osteogenic gene expression.

Science.gov (United States)

Ravichandran, Akhilandeshwari; Wen, Feng; Lim, Jing; Chong, Mark Seow Khoon; Chan, Jerry K Y; Teoh, Swee-Hin

2018-04-01

Cells respond to physiological mechanical stresses especially during early fetal development. Adopting a biomimetic approach, it is necessary to develop bioreactor systems to explore the effects of physiologically relevant mechanical strains and shear stresses for functional tissue growth and development. This study introduces a multimodal bioreactor system that allows application of cyclic compressive strains on premature bone grafts that are cultured under biaxial rotation (chamber rotation about 2 axes) conditions for bone tissue engineering. The bioreactor is integrated with sensors for dissolved oxygen levels and pH that allow real-time, non-invasive monitoring of the culture parameters. Mesenchymal stem cells-seeded polycaprolactone-β-tricalcium phosphate scaffolds were cultured in this bioreactor over 2 weeks in 4 different modes-static, cyclic compression, biaxial rotation, and multimodal (combination of cyclic compression and biaxial rotation). The multimodal culture resulted in 1.8-fold higher cellular proliferation in comparison with the static controls within the first week. Two weeks of culture in the multimodal bioreactor utilizing the combined effects of optimal fluid flow conditions and cyclic compression led to the upregulation of osteogenic genes alkaline phosphatase (3.2-fold), osteonectin (2.4-fold), osteocalcin (10-fold), and collagen type 1 α1 (2-fold) in comparison with static cultures. We report for the first time, the independent and combined effects of mechanical stimulation and biaxial rotation for bone tissue engineering using a bioreactor platform with non-invasive sensing modalities. The demonstrated results show leaning towards the futuristic vision of using a physiologically relevant bioreactor system for generation of autologous bone grafts for clinical implantation. Copyright © 2018 John Wiley & Sons, Ltd.

The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals

DEFF Research Database (Denmark)

Nielsen, S D; Sørensen, T U; Aladdin, H

2000-01-01

This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo was ...

Charge initiation schemes for ensuring high-performance operation of cyclic-flow technology cyclic link

Directory of Open Access Journals (Sweden)

S. N. Zharikov

2017-09-01

Full Text Available The authors consider the issue of ensuring the quality of crushing rock mass by drilling and blasting method for high productivity of a cyclic link of a cyclic-flow technology complex. The article contains recommendations for calculating certain parameters of drilling and blasting operations, such as the width of the retaining wall Bp. s, the collapse with account for the retaining wall Вr, the width of the collapse of the rock mass Bf when blasting onto a free surface (for the first row of vertical wells and for the first series of inclined wells, the width of the collapse from the first series of wells B1, the deceleration time τ, the coefficient kβ that takes into account the incline angle of wells β to the horizon. The authors prove the expediency of using a retaining wall in explosions of technological blocks. The authors raise the question about the management of detonation characteristics of explosives produced in the field of application for the most rational impact of an explosion on a rock massif. Since the technological schemes for preparing the rock mass to the excavation, which ensure the high-performance operation of the cyclic link of the cyclic-flow technology, can be different, then the choice of a specific drilling and blasting circuit is depends on the geological conditions and elements of the development system. As a preliminary method of breaking, one can consider the explosion of charges along the diagonal (diagonal blasting schemes on the retaining wall. This method provides sufficient reliability of technological explosions, and with the development of modern means of blasting with decelerations between charges of more than 67 ms, there are nearly no back emissions.

Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors.

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Devandir Antonio de Souza Junior

Full Text Available Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7 in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization.

Cyclic Matching Pursuits with Multiscale Time-frequency Dictionaries

DEFF Research Database (Denmark)

Sturm, Bob L.; Christensen, Mads Græsbøll

2010-01-01

We generalize cyclic matching pursuit (CMP), propose an orthogonal variant, and examine their performance using multiscale time-frequency dictionaries in the sparse approximation of signals. Overall, we find that the cyclic approach of CMP produces signal models that have a much lower approximation...

Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

Science.gov (United States)

Bergstrom, B P; Garris, P A

1999-03-01

The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

Stability of 2 ',3 ' and 3 ',5 ' cyclic nucleotides in formamide and in water: a theoretical insight into the factors controlling the accumulation of nucleic acid building blocks in a prebiotic pool

Czech Academy of Sciences Publication Activity Database

Cassone, Giuseppe; Šponer, Jiří; Saija, F.; Di Mauro, E.; Saitta, A. M.; Šponer, Judit E.

2017-01-01

Roč. 19, č. 3 (2017), s. 1817-1825 ISSN 1463-9076 R&D Projects: GA ČR(CZ) GA14-12010S Institutional support: RVO:68081707 Keywords : density- functional theory * liquid formamide * 2,3-cyclic nucleotides * molecular-dynamics Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 4.123, year: 2016

Association of Marijuana Use and Cyclic Vomiting Syndrome

Directory of Open Access Journals (Sweden)

Mithun B. Pattathan

2012-06-01

Full Text Available Cannabis use has become one of the most commonly abused drugs in the world. It is estimated that each year 2.6 million individuals in the USA become new users and most are younger than 19 years of age. Reports describe marijuana use as high as 40–50% in male Cyclic Vomiting Syndrome patients. It is this interest in cannabis in the World, coupled with recognition of a cyclic vomiting illness associated with its chronic use that beckons a review of the most current articles, as well as a contribution from our own experiences in this area. The similarities we have demonstrated for both cannibinoid hyperemesis syndrome and cyclic vomiting make the case that cannibinoid hyperemesis syndrome is a subset of patients who have the diagnoses of cyclic vomiting syndrome and the role of marijuana should always be considered in the diagnosis of CVS, particularly in males.

Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

Directory of Open Access Journals (Sweden)

Michel Alexandre Yazbek

2011-01-01

Full Text Available INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82. In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9. CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking

Design of a cyclic multiverse

Energy Technology Data Exchange (ETDEWEB)

Piao Yunsong, E-mail: yspiao@gucas.ac.c [College of Physical Sciences, Graduate School of Chinese Academy of Sciences, Beijing 100049 (China)

2010-08-09

Recently, it has been noticed that the amplification of the amplitude of curvature perturbation cycle by cycle can lead to a cyclic multiverse scenario, in which the number of universes increases cycle by cycle. However, this amplification will also inevitably induce either the ultimate end of corresponding cycle, or the resulting spectrum of perturbations inside corresponding universe is not scale invariant, which baffles the existence of observable universes. In this Letter, we propose a design of a cyclic multiverse, in which the observable universe can emerges naturally. The significance of a long period of dark energy before the turnaround of each cycle for this implementing is shown.

Design of a cyclic multiverse

International Nuclear Information System (INIS)

Piao Yunsong

2010-01-01

Recently, it has been noticed that the amplification of the amplitude of curvature perturbation cycle by cycle can lead to a cyclic multiverse scenario, in which the number of universes increases cycle by cycle. However, this amplification will also inevitably induce either the ultimate end of corresponding cycle, or the resulting spectrum of perturbations inside corresponding universe is not scale invariant, which baffles the existence of observable universes. In this Letter, we propose a design of a cyclic multiverse, in which the observable universe can emerges naturally. The significance of a long period of dark energy before the turnaround of each cycle for this implementing is shown.

The cyclical character of economic policy in Serbia 2001-2012

Directory of Open Access Journals (Sweden)

Radović-Stojanović Jelena

2014-01-01

Full Text Available This paper investigates the cyclical character of economic policy in Serbia in the period 2001-2012. For this purpose the cyclical movement of the following monetary and fiscal variables have been analysed: M2 money supply, the retail price index, the consumer price index, and the real effective exchange rate as the monetary policy indicators, and budget revenues and budget expenditures as the fiscal policy indicators. In the evaluation of the cyclical character of the economic policy, cross-correlation between the cyclical component of economic policy indicators and the gross domestic product at various lags has been observed. The results of cross-correlation analysis suggest that the budget expenditures are countercyclical and lead the aggregate cycle while the budget revenues are procyclical. The cyclical character of M2 money supply in the Serbian economy is somewhat contradictory, so further investigations of the cyclical character of monetary policy and mutual interdependence of money and output are required. The real effective exchange rate is countercyclical. The prices are procyclical and lag behind the cycles in aggregate economic activity. The procyclical character of prices indicates that the causes of the cyclical fluctuations of aggregate economic activities in Serbia in the period from 2001 to 2012 were on the demand side.

Elevational gradient in the cyclicity of a forest-defoliating insect

Science.gov (United States)

Kyle J. Haynes; Andrew M. Liebhold; Derek M. Johnson

2012-01-01

Observed changes in the cyclicity of herbivore populations along latitudinal gradients and the hypothesis that shifts in the importance of generalist versus specialist predators explain such gradients has long been a matter of intense interest. In contrast, elevational gradients in population cyclicity are largely unexplored. We quantified the cyclicity of gypsy moth...

Robust Cyclic MUSIC Algorithm for Finding Directions in Impulsive Noise Environment

Directory of Open Access Journals (Sweden)

Sen Li

2017-01-01

Full Text Available This paper addresses the issue of direction finding of a cyclostationary signal under impulsive noise environments modeled by α-stable distribution. Since α-stable distribution does not have finite second-order statistics, the conventional cyclic correlation-based signal-selective direction finding algorithms do not work effectively. To resolve this problem, we define two robust cyclic correlation functions which are derived from robust statistics property of the correntropy and the nonlinear transformation, respectively. The MUSIC algorithm with the robust cyclic correlation matrix of the received signals of arrays is then used to estimate the direction of cyclostationary signal in the presence of impulsive noise. The computer simulation results demonstrate that the two proposed robust cyclic correlation-based algorithms outperform the conventional cyclic correlation and the fractional lower order cyclic correlation based methods.

Human Granulocyte Colony-Stimulating Factor (hG-CSF) Expression in Plastids of Lactuca sativa

OpenAIRE

Sharifi Tabar, Mehdi; Habashi, Ali Akbar; Rajabi Memari, Hamid

2013-01-01

Background: Human granulocyte colony-stimulating factor (hG-CSF) can serve as valuable biopharmaceutical for research and treatment of the human blood cancer. Transplastomic plants have been emerged as a new and high potential candidate for production of recombinant biopharmaceutical proteins in comparison with transgenic plants due to extremely high level expression, biosafety and many other advantages. Methods: hG-CSF gene was cloned into pCL vector between prrn16S promoter and TpsbA ter...

Engineering a pharmacologically superior form of granulocyte-colony-stimulating factor by fusion with gelatin-like-protein polymer.

Science.gov (United States)

Huang, Yan-Shan; Wen, Xiao-Fang; Wu, Yi-Liang; Wang, Ye-Fei; Fan, Min; Yang, Zhi-Yu; Liu, Wei; Zhou, Lin-Fu

2010-03-01

The plasma half-life of therapeutic proteins is a critical factor in many clinical applications. Therefore, new strategies to prolong plasma half-life of long-acting peptides and protein drugs are in high demand. Here, we designed an artificial gelatin-like protein (GLK) and fused this hydrophilic GLK polymer to granulocyte-colony-stimulating factor (G-CSF) to generate a chimeric GLK/G-CSF fusion protein. The genetically engineered recombinant GLK/G-CSF (rGLK/G-CSF) fusion protein was purified from Pichia pastoris. In vitro studies demonstrated that rGLK/G-CSF possessed an enlarged hydrodynamic radius, improved thermal stability and retained full bioactivity compared to unfused G-CSF. Following a single subcutaneous administration to rats, the rGLK/G-CSF fusion protein displayed a slower plasma clearance rate and stimulated greater and longer lasting increases in circulating white blood cells than G-CSF. Our findings indicate that fusion with this artificial, hydrophilic, GLK polymer provides many advantages in the construction of a potent hematopoietic factor with extended plasma half-life. This approach could be easily applied to other therapeutic proteins and have important clinical applications. (c) 2009 Elsevier B.V. All rights reserved.

Centrifuge modelling of a laterally cyclic loaded pile

DEFF Research Database (Denmark)

Klinkvort, Rasmus Tofte; Leth, Caspar Thrane; Hededal, Ole

2010-01-01

A total number of 9 static and 6 cyclic centrifuge tests on laterally loaded piles in very dense, dry sand was erformed. The prototype dimensions of the piles were 1 meter in diameter and penetration depths varying from 6 to 10 meters. The static tests were used to investigate the initial subgrade...... reaction modulus and as a reference for cyclic tests. For the cyclic tests the accumulation of deflections and the change in secant stiffness of the soil from repetitive loading were investigated. From all the tests carried out accumulations of deflections were seen. rom the centrifuge tests it was seen...

Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan synthesis and expression of growth factor-related genes in human nucleus pulposus cell line

Directory of Open Access Journals (Sweden)

Y Kobayashi

2009-06-01

Full Text Available Low-intensity pulsed ultrasound (LIPUS stimulation has been shown to effect differentiation and activation of human chondrocytes. A study involving stimulation of rabbit disc cells with LIPUS revealed upregulation of cell proliferation and proteoglycan (PG synthesis. However, the effect of LIPUS on human nucleus pulposus cells has not been investigated. In the present study, therefore, we investigated whether LIPUS stimulation of a human nucleus pulposus cell line (HNPSV-1 exerted a positive effect on cellular activity. HNPSV-1 cells were encapsulated in 1.2% sodium alginate solution at 1x105 cells/ml and cultured at 10 beads/well in 6-well plates. The cells were stimulated for 20 min each day using a LIPUS generator, and the effects of LIPUS were evaluated by measuring DNA and PG synthesis. Furthermore, mRNA expression was analyzed by cDNA microarray using total RNA extracted from the cultured cells. Our study revealed no significant difference in cell proliferation between the control and the ultrasound treated groups. However, PG production was significantly upregulated in HNPSV cells stimulated at intensities of 15, 30, 60, and 120 mW/cm2 compared with the control. The results of cDNA array showed that LIPUS significantly stimulated the gene expression of growth factors and their receptors (BMP2, FGF7, TGFbetaR1 EGFRF1, VEGF. These findings suggest that LIPUS stimulation upregulates PG production in human nucleus pulposus cells by the enhancement of several matrix-related genes including growth factor-related genes. Safe and non-invasive stimulation using LIPUS may be a useful treatment for delaying the progression of disc degeneration.

Accelerate Genomic Aging in Congenital Neutropenia

Science.gov (United States)

2017-10-01

reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...neutropenia; Shwachman Diamond syndrome; Cyclic neutropenia; Hematopoietic stem cells; Granulocyte colony- stimulating factor; Acute myeloid leukemia...high rate of leukemic transformation. For example, granulocyte colony stimulating factor (G-CSF) expression is induced by neutropenia and may increase

Cyclic and heteroclinic flows near general static spherically symmetric black holes: semi-cyclic flows - addendum and corrigendum

Energy Technology Data Exchange (ETDEWEB)

Azreg-Ainou, Mustapha [Baskent University, Engineering Faculty, Ankara (Turkey)

2017-01-15

We present new accretion solutions of a polytropic perfect fluid onto an f(R)-gravity de Sitter-like black hole. We consider two f(R)-gravity models and obtain finite-period cyclic flows oscillating between the event and cosmological horizons as well as semi-cyclic critical flows executing a two-way motion from and back to the same horizon. Besides the generalizations and new solutions presented in this work, a corrigendum to Eur. Phys. J. C (2016) 76:280 is provided. (orig.)

Radioprotection of mouse intestine by inhibitors of cyclic amp phosphodiesterase

International Nuclear Information System (INIS)

Lehnert, S.

1979-01-01

The survival of colony-forming units of the jejunal crypt was used to assay the radioprotective capacity of various inhibitors of cyclic AMP phosphodiesterase. DL-152, RO-20-1724 and the methyl xanthines, caffeine, theophylline, and methyl isbutyl xanthine (MIX) were all found to have some radioprotective effect. The degree of radioprotecton depended on the route of administration of the drug and on the timing of administration with respect to irradiation. Optimum survival of crypt stem cells was found following intraperitoneal administration of DL-152 (60 min before irradiation) or MIX (30 min before irradiaton), and following intravenous administration of caffeine (60 to 120 min before irradiaton) or theophylline (60 min before irradiation). When these protocols were used, crypt stem cell survival could be enhanced by a factor of from 6 to 7. All the compounds investigated produced some elevation of cyclic AMP content of the whole jejunum; this was found to be simultaneous with or to precede the period of maximum radioprotection. Cyclic AMP was localized with immunofluorescent staining; following injection of DL-152 it was found to be elevated in all parts of the jejunum but to the greatest extent in the lower part of the crypt. Survival curves for crypt stem cells from MIX and DL-152 treated mice were found to have almost the same exponential slope as the saline-injected control, suggesting that the mechanism of protection does not depend on induction of hypoxia

Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

Science.gov (United States)

Xu, Peng; Andreasen, Peter A.; Huang, Mingdong

2017-01-01

This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively. The following affinity maturations significantly enhanced the potencies of the two peptides, 10-fold and >250-fold for upain-1 and mupain-1, respectively. The most potent muPA inhibitor has a potency (Ki = 2 nM) and specificity comparable to mono-clonal antibodies. Furthermore, we also found an unusual feature of mupain-1 that its inhibitory potency can be enhanced by increasing the flexibility, which challenges the traditional viewpoint that higher rigidity leading to higher affinity. Moreover, by changing a few key residues, we converted mupain-1 from a uPA inhibitor to inhibitors of other serine proteases, including plasma kallikrein (PK) and coagulation factor XIa (fXIa). PK and fXIa inhibitors showed Ki values in the low nanomolar range and high specificity. Our studies demonstrate the versatility of small cyclic peptides to engineer inhibitory potency against serine proteases and to provide a new strategy for generating peptide inhibitors of serine proteases. PMID:29104489

HOST liner cyclic facilities

Science.gov (United States)

Schultz, D.

1983-01-01

The HOST Liner Cyclic Program is utilizing two types of test apparatus, rectangular box rigs and a full annular rig. To date two quartz lamp cyclic box rigs have been tested and a third is to begin testing in late October 1983. The box rigs are used to evaluate 5x8 inch rectangular linear samples. A 21 inch diameter outer liner simulator is also being built up for testing beginning in April 1984. All rigs are atmospheric rigs. The first box rig, a three 6-kVA lamp installation, was operated under adverse conditions to determine feasibility of using quartz lamps for cyclic testing. This work was done in December 1981 and looked promising. The second box rig, again using three 6-kVA lamps, was operated to obtain instrumentation durability information and initial data input to a Finite Element Model. This limited test program was conducted in August 1983. Five test plates were run. Instrumentation consisted of strain gages, thermocouples and thermal paint. The strain gages were found to fail at 1200 F as expected though plates were heated to 1700 F. The third box rig, containing four 6-kVA lamps, is in build up for testing to begin in late October 1983. In addition to 33 percent greater power input, this rig has provision for 400 F backside line cooling air and a viewing port suitable for IR camera viewing. The casing is also water cooled for extended durability.

Effects of cyclic mean pressure of helium gas on performance of integral crank driven stirling cryocooler

Energy Technology Data Exchange (ETDEWEB)

Hong, Yong Ju; Ko, Jun Seok; Kim, Hyo Bong; Park, Seong Je [Korea Institute of Machinery and Materials, Changwon (Korea, Republic of)

2016-09-15

An integral crank driven Stirling cryocooler is solidly based on concepts of direct IR detector mounting on the cryocooler's cold finger, and the integral construction of the cryocooler and Dewar envelope. Performance factors of the cryocooler depend on operating conditions of the cryocooler such as a cyclic mean pressure of the working fluid, a rotational speed of driving mechanism, a thermal environment, a targeted operation temperature and etc.. At given charging condition of helium gas, the cyclic mean pressure of helium gas in the cryocooler changes with temperatures of the cold end and the environment. In this study, effects of the cyclic mean pressure of helium gas on performances of the Stirling cryocooler were investigated by numerical analyses using the Sage software. The simulation model takes into account thermodynamic losses due to an inefficiency of regenerator, a pressure drop, a shuttle heat transfer and solid conductions. Simulations are performed for the performance variation according to the cyclic mean pressure induced by the temperature of the cold end and the environment. This paper presents P-V works in the compression and expansion space, cooling capacity, contribution of losses in the expansion space.

Effects of cyclic mean pressure of helium gas on performance of integral crank driven stirling cryocooler

International Nuclear Information System (INIS)

Hong, Yong Ju; Ko, Jun Seok; Kim, Hyo Bong; Park, Seong Je

2016-01-01

An integral crank driven Stirling cryocooler is solidly based on concepts of direct IR detector mounting on the cryocooler's cold finger, and the integral construction of the cryocooler and Dewar envelope. Performance factors of the cryocooler depend on operating conditions of the cryocooler such as a cyclic mean pressure of the working fluid, a rotational speed of driving mechanism, a thermal environment, a targeted operation temperature and etc.. At given charging condition of helium gas, the cyclic mean pressure of helium gas in the cryocooler changes with temperatures of the cold end and the environment. In this study, effects of the cyclic mean pressure of helium gas on performances of the Stirling cryocooler were investigated by numerical analyses using the Sage software. The simulation model takes into account thermodynamic losses due to an inefficiency of regenerator, a pressure drop, a shuttle heat transfer and solid conductions. Simulations are performed for the performance variation according to the cyclic mean pressure induced by the temperature of the cold end and the environment. This paper presents P-V works in the compression and expansion space, cooling capacity, contribution of losses in the expansion space

THE STRENGTH OF REINFORCED CONCRETE BEAM ELEMENTS UNDER CYCLIC ALTERNATING LOADING AND LOW CYCLE LOAD OF CONSTANT SIGN

Directory of Open Access Journals (Sweden)

Semina Yuliya Anatol'evna

2015-09-01

Full Text Available The behavior of reinforced concrete elements under some types of cyclic loads is described in the paper. The main aim of the investigations is research of the stress-strain state and strength of the inclined sections of reinforced concrete beam elements in conditions of systemic impact of constructive factors and the factor of external influence. To spotlight the problem of cyclic loadings three series of tests were conducted by the author. Firstly, the analysis of the tests showed that especially cyclic alternating loading reduces the bearing capacity of reinforced concrete beams and their crack resistance by 20 % due to the fatigue of concrete and reinforcement. Thus the change of load sign creates serious changes of stress-strain state of reinforced concrete beam elements. Low cycle loads of constant sign effect the behavior of the constructions not so adversely. Secondly, based on the experimental data mathematical models of elements’ strength were obtained. These models allow evaluating the impact of each factor on the output parameter not only separately, but also in interaction with each other. Furthermore, the material spotlighted by the author describes stress-strain state of the investigated elements, cracking mechanism, changes of deflection values, the influence of mode cyclic loading during the tests. Since the data on the subject are useful and important to building practice, the ultimate aim of the tests will be working out for improvement of nonlinear calculation models of span reinforced concrete constructions taking into account the impact of these loads, and also there will be the development of engineering calculation techniques of their strength, crack resistance and deformability.

Regulation of Cancer Cell Responsiveness to Ionizing Radiation Treatment by Cyclic AMP Response Element Binding Nuclear Transcription Factor

Directory of Open Access Journals (Sweden)

Francesca D’Auria

2017-05-01

Full Text Available Cyclic AMP response element binding (CREB protein is a member of the CREB/activating transcription factor (ATF family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR therapy, demonstrating a relationship between IR-induced CREB family members’ activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562. On the other hand, a number of evidences highlight a proapoptotic role of CREB following IR treatment of cancer cells. Since the development of multiple mechanisms of resistance is one key problem of most malignancies, including those of hematological origin, it is highly desirable to identify biological markers of responsiveness/unresponsiveness useful to follow-up the individual response and to adjust anticancer treatments. Taking into account all these considerations, this mini-review will be focused on the involvement of CREB/ATF family members in response to IR therapy, to deepen our knowledge of this topic, and to pave the way to translation into a therapeutic context.

Evolutive masing model, cyclic plasticity, ageing and memory effects

International Nuclear Information System (INIS)

Sidoroff, F.

1987-01-01

Many models are proposed for the mechanical description of the cyclic behaviour of metals and used for structure analysis under cyclic loading. Such a model must include two basic features: Dissipative behaviour on each cycle (hysteresis loop); evolution of this behaviour during the material's life (cyclic hardening or softening, aging,...). However, if both aspects are present in most existing models, the balance between them may be quite different. Many metallurgical investigations have been performed about the microstructure and its evolution during cyclic loading, and it is desirable to introduce these informations in phenomenological models. The evolutive Masing model has been proposed to combine: the accuracy of hereditary models for the description of hysteresis on each cycle, the versatility of internal variables for the state description and evolution, a sufficient microstructural basis to make the interaction easier with microstructural investigations. The purpose of the present work is to discuss this model and to compare different evolution assumptions with respect to some memory effects (cyclic hardening and softening, multilevel tests, aging). Attention is limited to uniaxial, rate independent elasto-plastic behaviour

The enzymatic preparation of [α-32P]nucleoside triphosphates, cyclic [32P]AMP, and cyclic [32P]GMP

International Nuclear Information System (INIS)

Walseth, T.F.; Johnson, R.A.

1979-01-01

A method has been developed for the enzymatic preparation of α- 32 P-labelled ribo- and deoxyribonucleoside triphosphates, cyclic [ 32 P]AMP, and cyclic [ 32 P]GMP of high specific radioactivity and in high yield from 32 Psub(i). The method also enables the preparation of [γ- 32 P]ATP, [γ- 32 P]GTP, [γ- 32 P]ITP, and [γ- 32 P]-dATP of very high specific activity and in high yield. (Auth.)

Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor

International Nuclear Information System (INIS)

Mochizuki, D.Y.; Eisenman, J.R.; Conlon, P.J.; Park, L.S.; Urdal, D.L.

1986-01-01

The expression in yeast of a cDNA clone encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has made possible the purification of large quantities of this recombinant protein. Rabbits immunized with pure recombinant GM-CSF generated antibodies that were shown to be specific for both recombinant GM-CSF and GM-CSF isolated from natural sources. Other lymphokines, including IL 1β, IL 2, IL 3, and recombinant human GM-CSF did not react with the antiserum. The antiserum together with recombinant GM-CSF that had been radiolabeled with 125 I to high specific activity, formed the foundation for a rapid, sensitive, and quantitative radioimmunoassay specific for murine GM-CSF. Furthermore, the antiserum was found to inhibit the biologic activities of GM-CSF as measured in both a bone marrow proliferation assay and a colony assay, and thus should prove to be a useful reagent for dissecting the complex growth factor activities involved in murine hematopoiesis

Myeloprotective Action of Combined Application of Ukrainian Recombinant Granulocyte Colony Stimulating Factor (r-GCSF and Enterosorbent С2 in Rats with Malignant Guerin Carcinoma

Directory of Open Access Journals (Sweden)

Todor, I.M.

2015-03-01

Full Text Available The aim of the study is to analyze myeloprotective effect of novel enterosorbents alone and in combination with two recombinant granulocyte colony stimulating factors: Neupogen (Switzerland and r- GCSF (Ukraine. It is proven that Ukrainian version of recombinant granulocyte colony stimulating factor r-GCSF does not concede officinal drug Neupogen (Switzerland by its experimental therapeutic action and combined use with enterosorbent C2 significantly increases myeloprotective effect of both GCSF versions.

Aliphatic, cyclic, and aromatic organic acids, vitamins, and carbohydrates in soil: a review.

Science.gov (United States)

Vranova, Valerie; Rejsek, Klement; Formanek, Pavel

2013-11-10

Organic acids, vitamins, and carbohydrates represent important organic compounds in soil. Aliphatic, cyclic, and aromatic organic acids play important roles in rhizosphere ecology, pedogenesis, food-web interactions, and decontamination of sites polluted by heavy metals and organic pollutants. Carbohydrates in soils can be used to estimate changes of soil organic matter due to management practices, whereas vitamins may play an important role in soil biological and biochemical processes. The aim of this work is to review current knowledge on aliphatic, cyclic, and aromatic organic acids, vitamins, and carbohydrates in soil and to identify directions for future research. Assessments of organic acids (aliphatic, cyclic, and aromatic) and carbohydrates, including their behaviour, have been reported in many works. However, knowledge on the occurrence and behaviour of D-enantiomers of organic acids, which may be abundant in soil, is currently lacking. Also, identification of the impact and mechanisms of environmental factors, such as soil water content, on carbohydrate status within soil organic matter remains to be determined. Finally, the occurrence of vitamins in soil and their role in biological and biochemical soil processes represent an important direction for future research.

Aliphatic, Cyclic, and Aromatic Organic Acids, Vitamins, and Carbohydrates in Soil: A Review

Directory of Open Access Journals (Sweden)

Valerie Vranova

2013-01-01

Full Text Available Organic acids, vitamins, and carbohydrates represent important organic compounds in soil. Aliphatic, cyclic, and aromatic organic acids play important roles in rhizosphere ecology, pedogenesis, food-web interactions, and decontamination of sites polluted by heavy metals and organic pollutants. Carbohydrates in soils can be used to estimate changes of soil organic matter due to management practices, whereas vitamins may play an important role in soil biological and biochemical processes. The aim of this work is to review current knowledge on aliphatic, cyclic, and aromatic organic acids, vitamins, and carbohydrates in soil and to identify directions for future research. Assessments of organic acids (aliphatic, cyclic, and aromatic and carbohydrates, including their behaviour, have been reported in many works. However, knowledge on the occurrence and behaviour of D-enantiomers of organic acids, which may be abundant in soil, is currently lacking. Also, identification of the impact and mechanisms of environmental factors, such as soil water content, on carbohydrate status within soil organic matter remains to be determined. Finally, the occurrence of vitamins in soil and their role in biological and biochemical soil processes represent an important direction for future research.

Aliphatic, Cyclic, and Aromatic Organic Acids, Vitamins, and Carbohydrates in Soil: A Review

Science.gov (United States)

Vranova, Valerie; Rejsek, Klement; Formanek, Pavel

2013-01-01

Organic acids, vitamins, and carbohydrates represent important organic compounds in soil. Aliphatic, cyclic, and aromatic organic acids play important roles in rhizosphere ecology, pedogenesis, food-web interactions, and decontamination of sites polluted by heavy metals and organic pollutants. Carbohydrates in soils can be used to estimate changes of soil organic matter due to management practices, whereas vitamins may play an important role in soil biological and biochemical processes. The aim of this work is to review current knowledge on aliphatic, cyclic, and aromatic organic acids, vitamins, and carbohydrates in soil and to identify directions for future research. Assessments of organic acids (aliphatic, cyclic, and aromatic) and carbohydrates, including their behaviour, have been reported in many works. However, knowledge on the occurrence and behaviour of D-enantiomers of organic acids, which may be abundant in soil, is currently lacking. Also, identification of the impact and mechanisms of environmental factors, such as soil water content, on carbohydrate status within soil organic matter remains to be determined. Finally, the occurrence of vitamins in soil and their role in biological and biochemical soil processes represent an important direction for future research. PMID:24319374

mMass as a Software Tool for the Annotation of Cyclic Peptide Tandem Mass Spectra

Czech Academy of Sciences Publication Activity Database

Niedermeyer, T. H. J.; Strohalm, Martin

2012-01-01

Roč. 7, č. 9 (2012), e44913 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) ME10013 Institutional research plan: CEZ:AV0Z50200510 Keywords : cyclic peptides * nMass Subject RIV: CE - Biochemistry Impact factor: 3.730, year: 2012

Skin complications in deep brain stimulation for Parkinson's disease: frequency, time course, and risk factors.

Science.gov (United States)

Sixel-Döring, Friederike; Trenkwalder, Claudia; Kappus, Christoph; Hellwig, Dieter

2010-02-01

Deep brain stimulation (DBS) has been recognized as an efficacious treatment for movement disorders. Its beneficial effects however may be lost due to skin complications such as erosions or infections over the implanted foreign material. We sought to document skin complications in the entire Parkinson's disease patient population who received a DBS system at the Marburg/Kassel implantation centre since the start of our DBS program in January 2002 to analyze frequency, time course, and possible risk factors. We investigated 85 consecutive patients with Parkinson's disease (PD) from a single center/single surgeon DBS series for the occurrence of skin complications and analyzed localization, time course, and possible risk factors. Mean follow-up was 3 years (range 1-7 years). In total, 21/85 patients (24.7%) suffered a total of 30 single skin complications. Sixty percent of all incidents occurred within the first post-operative year. Forty percent of all incidents occurred later than the first year following primary implantation. Complications involved the burr hole cap in 37%, the course of the cables in 33%, and the impulse generator (IPG) site in 30%. Six of 21 patients suffered recurring skin complications. Eight patients permanently lost their DBS system. Factor analysis for age, gender, disease duration, disease severity, the incidence of hypertension or diabetes as well as a 2-day period with externalized electrodes for continuous test stimulation did not have any statistically significant impact on skin complications. We conclude that (1) PD patients have a risk for skin complications after DBS as long as the system remains in situ and (2) there are at present no identifiable risk factors for skin complications after DBS, other than PD itself.

Electrooxidation of activated alpha,omega-diols to cyclic tetramethylene acetals of the corresponding dials

Czech Academy of Sciences Publication Activity Database

Hlavatý, Jaromír; Polášek, Miroslav

2006-01-01

Roč. 47, č. 44 (2006), s. 7789-7791 ISSN 0040-4039 R&D Projects: GA ČR GA203/03/0825 Institutional research plan: CEZ:AV0Z40400503 Keywords : anodic oxidation * cyclic tetramethylene acetals * 2,7-dioxepyl derivatives Subject RIV: CG - Electrochemistry Impact factor: 2.509, year: 2006

Identification of cyclic nucleotide gated channels using regular expressions

KAUST Repository

Zelman, Alice K.; Dawe, Adam Sean; Berkowitz, Gerald A.

2013-01-01

Cyclic nucleotide-gated channels (CNGCs) are nonselective cation channels found in plants, animals, and some bacteria. They have a six-transmembrane/one- pore structure, a cytosolic cyclic nucleotide-binding domain, and a cytosolic calmodulin

Cyclic plasticity models and application in fatigue analysis

Science.gov (United States)

Kalev, I.

1981-01-01

An analytical procedure for prediction of the cyclic plasticity effects on both the structural fatigue life to crack initiation and the rate of crack growth is presented. The crack initiation criterion is based on the Coffin-Manson formulae extended for multiaxial stress state and for inclusion of the mean stress effect. This criterion is also applied for the accumulated damage ahead of the existing crack tip which is assumed to be related to the crack growth rate. Three cyclic plasticity models, based on the concept of combination of several yield surfaces, are employed for computing the crack growth rate of a crack plane stress panel under several cyclic loading conditions.

The mycotoxin definition reconsidered towards fungal cyclic depsipeptides.

Science.gov (United States)

Taevernier, Lien; Wynendaele, Evelien; De Vreese, Leen; Burvenich, Christian; De Spiegeleer, Bart

2016-04-02

Currently, next to the major classes, cyclic depsipeptides beauvericin and enniatins are also positioned as mycotoxins. However, as there are hundreds more fungal cyclic depsipeptides already identified, should these not be considered as mycotoxins as well? The current status of the mycotoxin definition revealed a lack of consistency, leading to confusion about what compounds should be called mycotoxins. Because this is of pivotal importance in risk assessment prioritization, a clear and quantitatively expressed mycotoxin definition is proposed, based on data of widely accepted mycotoxins. Finally, this definition is applied to a set of fungal cyclic depsipeptides, revealing that some of these should indeed be considered as mycotoxins.

Holographic entanglement entropy and cyclic cosmology

Science.gov (United States)

Frampton, Paul H.

2018-06-01

We discuss a cyclic cosmology in which the visible universe, or introverse, is all that is accessible to an observer while the extroverse represents the total spacetime originating from the time when the dark energy began to dominate. It is argued that entanglement entropy of the introverse is the more appropriate quantity to render infinitely cyclic, rather than the entropy of the total universe. Since vanishing entanglement entropy implies disconnected spacetimes, at the turnaround when the introverse entropy is zero the disconnected extroverse can be jettisoned with impunity.

Combined Stimulation with the Tumor Necrosis Factor α and the Epidermal Growth Factor Promotes the Proliferation of Hepatocytes in Rat Liver Cultured Slices

Directory of Open Access Journals (Sweden)

Francis Finot

2012-01-01

Full Text Available The culture liver slices are mainly used to investigate drug metabolism and xenobiotic-mediated liver injuries while apoptosis and proliferation remain unexplored in this culture model. Here, we show a transient increase in LDH release and caspase activities indicating an ischemic injury during the slicing procedure. Then, caspase activities decrease and remain low in cultured slices demonstrating a low level of apoptosis. The slicing procedure is also associated with the G0/G1 transition of hepatocytes demonstrated by the activation of stress and proliferation signalling pathways including the ERK1/2 and JNK1/2/3 MAPKinases and the transient upregulation of c-fos. The cells further progress up to mid-G1 phase as indicated by the sequential induction of c-myc and p53 mRNA levels after the slicing procedure and at 24 h of culture, respectively. The stimulation by epidermal growth factor induces the ERK1/2 phosphorylation but fails to activate expression of late G1 and S phase markers such as cyclin D1 and Cdk1 indicating that hepatocytes are arrested in mid-G1 phase of the cell cycle. However, we found that combined stimulation by the proinflammatory cytokine tumor necrosis factor α and the epidermal growth factor promotes the commitment to DNA replication as observed in vivo during the liver regeneration.

Transforming growth factor-beta 1 stimulates synthesis of proteoglycan aggregates in calf articular cartilage organ cultures

International Nuclear Information System (INIS)

Morales, T.I.

1991-01-01

Previous work showed that transforming growth factor-beta 1 (TGF-beta 1), added alone to bovine cartilage organ cultures, stimulated [35S]sulfate incorporation into macromolecular material but did not investigate the fidelity of the stimulated system to maintain synthesis of cartilage-type proteoglycans. This paper provides evidence that chondrocytes synthesize the appropriate proteoglycan matrix under TGF-beta 1 stimulation: (1) there is a coordinated increase in hyaluronic acid and proteoglycan monomer synthesis, (2) link-stable proteoglycan aggregates are assembled, (3) the hybrid chondroitin sulfate/keratan sulfate monomeric species is synthesized, and (4) there is an increase in protein core synthesis. Some variation in glycosylation patterns was observed when proteoglycans synthesized under TGF-beta 1 stimulation were compared to those synthesized under basal conditions. Thus comparing TGF-beta 1 to basal samples respectively, the monomers were larger (Kav on Sepharose CL-2B = 0.29 vs 0.41), the chondroitin sulfate chains were longer by approximately 3.5 kDa, the percentage of total glycosaminoglycan in keratan sulfate increased slightly from approximately 4% (basal) to approximately 6%, and the unsulfated disaccharide decreased from 28% (basal) to 12%. All of these variations are in the direction of a more anionic proteoglycan. Since the ability of proteoglycans to confer resiliency to the cartilage matrix is directly related to their anionic nature, these changes would presumably have a beneficial effect on tissue function

Test method research on weakening interface strength of steel - concrete under cyclic loading

Science.gov (United States)

Liu, Ming-wei; Zhang, Fang-hua; Su, Guang-quan

2018-02-01

The mechanical properties of steel - concrete interface under cyclic loading are the key factors affecting the rule of horizontal load transfer, the calculation of bearing capacity and cumulative horizontal deformation. Cyclic shear test is an effective method to study the strength reduction of steel - concrete interface. A test system composed of large repeated direct shear test instrument, hydraulic servo system, data acquisition system, test control software system and so on is independently designed, and a set of test method, including the specimen preparation, the instrument preparation, the loading method and so on, is put forward. By listing a set of test results, the validity of the test method is verified. The test system and the test method based on it provide a reference for the experimental study on mechanical properties of steel - concrete interface.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

Energy Technology Data Exchange (ETDEWEB)

Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C. (Univ. of California, San Francisco (USA))

1990-06-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection.

The effect of diet on tumor necrosis factor stimulation of hepatic lipogenesis

International Nuclear Information System (INIS)

Feingold, K.R.; Soued, M.; Serio, M.K.; Adi, S.; Moser, A.H.; Grunfeld, C.

1990-01-01

In this study, we determined the effects of tumor necrosis factor (TNF) on serum lipid levels and hepatic lipid synthesis in animals whose diets and feeding conditions were varied to induce changes in baseline serum lipid levels and/or rates of hepatic lipid synthesis. In animals studied at both the nadir and peak of the diurnal cycle of hepatic lipid synthesis, TNF acutely increases serum triglyceride levels, stimulates hepatic fatty acid synthesis, and increases the quantity of newly synthesized fatty acids found in the serum. Similarly, in animals ingesting either high-sucrose or cholesterol-enriched diets, TNF induces the characteristic rapid increase in serum triglyceride levels, hepatic fatty acid synthesis, and quantity of labeled fatty acids in the serum. In animals fed a diet high in triglycerides, using either corn oil or lard, TNF stimulates hepatic fatty acid synthesis and increases the quantity of newly synthesized fatty acids in the serum, but serum triglyceride levels do not change. However, TNF inhibits gastric emptying, which results in a marked decrease in fat absorption in TNF-treated animals. It is likely that a decrease in the dietary contribution to serum triglyceride levels during high-triglyceride feeding counterbalances the increased hepatic contribution induced by TNF treatment. In animals fasted before TNF administration there was no acute change in either serum lipid levels, hepatic fatty acid synthesis, or the quantity of labeled fatty acids in the serum. Thus, TNF stimulates hepatic fatty acid synthesis and increases serum triglyceride levels under many diverse dietary conditions, suggesting that there is a strong linkage between the immune system and lipid metabolism that is independent of most dietary manipulations and may be of fundamental importance in the body's response to infection

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans.

Science.gov (United States)

Gordon, Tessa

2016-04-01

Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

Glucose Stimulation of Transforming Growth Factor-β Bioactivity in Mesangial Cells Is Mediated by Thrombospondin-1

Science.gov (United States)

Poczatek, Maria H.; Hugo, Christian; Darley-Usmar, Victor; Murphy-Ullrich, Joanne E.

2000-01-01

Glucose is a key factor in the development of diabetic complications, including diabetic nephropathy. The development of diabetic glomerulosclerosis is dependent on the fibrogenic growth factor, transforming growth factor-β (TGF-β). Previously we showed that thrombospondin-1 (TSP-1) activates latent TGF-β both in vitro and in vivo. Activation occurs as the result of specific interactions of latent TGF-β with TSP-1, which potentially alter the conformation of latent TGF-β. As glucose also up-regulates TSP-1 expression, we hypothesized that the increased TGF-β bioactivity observed in rat and human mesangial cells cultured with high glucose concentrations is the result of latent TGF-β activation by autocrine TSP-1. Glucose-induced bioactivity of TGF-β in mesangial cell cultures was reduced to basal levels by peptides from two different sequences that antagonize activation of latent TGF-β by TSP, but not by the plasmin inhibitor, aprotinin. Furthermore, glucose-dependent stimulation of matrix protein synthesis was inhibited by these antagonist peptides. These studies demonstrate that glucose stimulation of TGF-β activity and the resultant matrix protein synthesis are dependent on the action of autocrine TSP-1 to convert latent TGF-β to its biologically active form. These data suggest that antagonists of TSP-dependent TGF-β activation may be the basis of novel therapeutic approaches for ameliorating diabetic renal fibrosis. PMID:11021838

Application of cyclic activation to in vivo elemental analysis

International Nuclear Information System (INIS)

Spyrou, N.M.

1984-01-01

Experience over the past seven years with a prototype cyclic system, based on an oscillating 5Ci AmBe neutron source, suggests that multielemental in vivo analysis is possible and more specifically indicates that the determination of selenium and cadmium in liver may allow the examination of the interaction of the two elements at acceptable doses. Detection limits obtained for selenium and cadmium, in the same experiment but through different modes of detection i.e. the measurement of delayed gamma-rays from short-lived Se-77m (17.6 s) and prompt gamma-rays from Cd-114, in a cyclic sequence of irradiations, are 0.4 ppm and 6 ppm respectively, for a total irradiation period of 1800s and an equivalent dose to the irradiated region of 5mSv. The redesigning of the prototype system is being considered in order to decrease the detection limit of selenium to a value of 0.1 ppm or less and the effect of increasing the neutron flux tenfold is investigated. This could result in an improvement by a factor of 4 to 5 in detection, for the same dose. 36 references, 6 figures

Effects of hypokinesia on cyclic nucleotides and hormonal regulation ...

African Journals Online (AJOL)

PTH), calcitonin (CT), cyclic nucleotides (cAMP, cGMP) and calcium in the blood of rats, while in urine - phosphate, calcium and cyclic nucleotides. Design: Laboratory based experiment. Setting: Laboratory in the Department of Biochemistry, ...

Evaluating cyclic fatigue of sealants during outdoor testing

Science.gov (United States)

R. Sam Williams; Steven Lacher; Corey Halpin; Christopher White

2009-01-01

A computer-controlled test apparatus (CCTA) and other instrumentation for subjecting sealant specimens to cyclic fatigue during outdoor exposure was developed. The CCTA enables us to use weather-induced conditions to cyclic fatigue specimens and to conduct controlled tests in-situ during the outdoor exposure. Thermally induced dimensional changes of an aluminum bar...

Cyclic inelastic deformation aspects of fatigue-crack-growth analysis

Energy Technology Data Exchange (ETDEWEB)

Leis, B.N.; Zahoor, A.

1980-01-01

This paper concentrates on a J-integral analysis of fatigue crack growth. Data on cyclic plasticity are analyzed showing that there are limitations to the usefulness of the deformation theory in applications to cyclic plasticity. 56 refs.

First attempts towards the early detection of fatigued substructures using cyclic-loaded 20 MnMoNi 5 5 steel

International Nuclear Information System (INIS)

Dobmann, G.; Seibold, A.

1992-01-01

Materials subjected to cyclic loading undergo substructural changes which may affect service life. The low alloy, fine-grained structural steel 20 MnMoNi 5 5 is used to demonstrate how substructural changes detected using TEM techniques are a function of the number of cycles undergone. For a given cyclic loading the usage factor η=N/N f =0.5 can be derived. Initial investigations using nondestructive examination methods have indicated that substructural changes and magnetic variables can be correlated. (orig.)

Investigation on effectiveness of a prefabricated vertical drain during cyclic loading

International Nuclear Information System (INIS)

Indraratna, B; Ni, J; Rujikiatkamjorn, C

2010-01-01

The effectiveness of prefabricated vertical drains (PVDs) in enhancing the stability of soft soils during cyclic loading was investigated using triaxial cyclic loading tests. Both undrained and with PVD tests were employed to study the associated excess pore pressure and accumulated strain under the repeated loading condition. The loading frequency and cyclic stress ratio have been chosen to be the variables which influence the performance of soft clays. The experimental results illustrate that with PVDs, the excess pore water pressure generation during cyclic loading decreases significantly. It is found that the excess pore water pressure build up depends on both loading frequency and cyclic stress ratio. The excess pore water pressure will increase when each of them is increased. Furthermore, when the loading frequency is 0.1 Hz, the ratio of coefficient of consolidation under cyclic loading to that under static loading is almost one. With the increasing loading frequency, this ratio increases accordingly.

Comparison of phosphorylation of ribosomal proteins from HeLa and Krebs II ascites-tumour cells by cyclic AMP-dependent and cyclic GMP-dependent protein kinases

DEFF Research Database (Denmark)

Issinger, O G; Beier, H; Speichermann, N

1980-01-01

Phosphorylation of eukaryotic ribosomal proteins in vitro by essentially homogeneous preparations of cyclic AMP-dependent protein kinase catalytic subunit and cyclic GMP-dependent protein kinase was compared. Each protein kinase was added at a concentration of 30nM. Ribosomal proteins were...... by the cyclic AMP-dependent enzyme. Between 0.1 and 0.2 mol of phosphate was incorporated/mol of these phosphorylated proteins. With the exception of protein S7, the same proteins were also major substrates for the cyclic GMP-dependent protein kinase. Time courses of the phosphorylation of individual proteins...... from the small and large ribosomal subunits in the presence of either protein kinase suggested four types of phosphorylation reactions: (1) proteins S2, S10 and L5 were preferably phosphorylated by the cyclic GMP-dependent protein kinase; (2) proteins S3 and L6 were phosphorylated at very similar rates...

Probabilistic Simulation of Combined Thermo-Mechanical Cyclic Fatigue in Composites

Science.gov (United States)

Chamis, Christos C.

2011-01-01

A methodology to compute probabilistically-combined thermo-mechanical fatigue life of polymer matrix laminated composites has been developed and is demonstrated. Matrix degradation effects caused by long-term environmental exposure and mechanical/thermal cyclic loads are accounted for in the simulation process. A unified time-temperature-stress-dependent multifactor-interaction relationship developed at NASA Glenn Research Center has been used to model the degradation/aging of material properties due to cyclic loads. The fast probability-integration method is used to compute probabilistic distribution of response. Sensitivities of fatigue life reliability to uncertainties in the primitive random variables (e.g., constituent properties, fiber volume ratio, void volume ratio, ply thickness, etc.) computed and their significance in the reliability-based design for maximum life is discussed. The effect of variation in the thermal cyclic loads on the fatigue reliability for a (0/+/-45/90)s graphite/epoxy laminate with a ply thickness of 0.127 mm, with respect to impending failure modes has been studied. The results show that, at low mechanical-cyclic loads and low thermal-cyclic amplitudes, fatigue life for 0.999 reliability is most sensitive to matrix compressive strength, matrix modulus, thermal expansion coefficient, and ply thickness. Whereas at high mechanical-cyclic loads and high thermal-cyclic amplitudes, fatigue life at 0.999 reliability is more sensitive to the shear strength of matrix, longitudinal fiber modulus, matrix modulus, and ply thickness.

Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

International Nuclear Information System (INIS)

Carter, M.G.; Shukla, S.D.

1987-01-01

Human platelet concentrate from the American Red Cross Blood Center was stored at 24 degree C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying 32 P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 x 10 -7 M PAF at 37 degree C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for 32 P-phosphoinositides. The percent stimulation of 32 P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

Energy Technology Data Exchange (ETDEWEB)

Kosheverova, Vera V., E-mail: kosheverova_vera@incras.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kamentseva, Rimma S., E-mail: rkamentseva@yandex.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Gonchar, Ilya V., E-mail: ample@mail.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kharchenko, Marianna V., E-mail: mariannakharchenko@gmail.com [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kornilova, Elena S., E-mail: lenkor@mail.cytspb.rssi.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, 29, Polytechnicheskaya, St.Petersburg, 195251 (Russian Federation)

2016-04-22

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

International Nuclear Information System (INIS)

Kosheverova, Vera V.; Kamentseva, Rimma S.; Gonchar, Ilya V.; Kharchenko, Marianna V.; Kornilova, Elena S.

2016-01-01

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

The Role of Cyclic Nucleotide Signaling Pathways in Cancer: Targets for Prevention and Treatment

Energy Technology Data Exchange (ETDEWEB)

Fajardo, Alexandra M.; Piazza, Gary A. [Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave, Suite 3029, Mobile, AL 36604 (United States); Tinsley, Heather N., E-mail: htinsley@montevallo.edu [Department of Biology, Chemistry, and Mathematics, University of Montevallo, Station 6480, Montevallo, AL 35115 (United States)

2014-02-26

For more than four decades, the cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP (cGMP) have been recognized as important signaling molecules within cells. Under normal physiological conditions, cyclic nucleotides regulate a myriad of biological processes such as cell growth and adhesion, energy homeostasis, neuronal signaling, and muscle relaxation. In addition, altered cyclic nucleotide signaling has been observed in a number of pathophysiological conditions, including cancer. While the distinct molecular alterations responsible for these effects vary depending on the specific cancer type, several studies have demonstrated that activation of cyclic nucleotide signaling through one of three mechanisms—induction of cyclic nucleotide synthesis, inhibition of cyclic nucleotide degradation, or activation of cyclic nucleotide receptors—is sufficient to inhibit proliferation and activate apoptosis in many types of cancer cells. These findings suggest that targeting cyclic nucleotide signaling can provide a strategy for the discovery of novel agents for the prevention and/or treatment of selected cancers.

Computational simulation of static/cyclic cell stimulations to investigate mechanical modulation of an individual mesenchymal stem cell using confocal microscopy

International Nuclear Information System (INIS)

Alihemmati, Zakieh; Vahidi, Bahman; Haghighipour, Nooshin; Salehi, Mohammad

2017-01-01

It has been found that cells react to mechanical stimuli, while the type and magnitude of these cells are different in various physiological and pathological conditions. These stimuli may affect cell behaviors via mechanotransduction mechanisms. The aim of this study is to evaluate mechanical responses of a mesenchymal stem cell (MSC) to a pressure loading using finite elements method (FEM) to clarify procedures of MSC mechanotransduction. The model is constructed based on an experimental set up in which statics and cyclic compressive loads are implemented on a model constructed from a confocal microscopy 3D image of a stem cell. Both of the applied compressive loads are considered in the physiological loading regimes. Moreover, a viscohyperelastic material model was assumed for the cell through which the finite elements simulation anticipates cell behavior based on strain and stress distributions in its components. As a result, high strain and stress values were captured from the viscohyperelastic model because of fluidic behavior of cytosol when compared with the obtained results through the hyperelastic models. It can be concluded that the generated strain produced by cyclic pressure is almost 8% higher than that caused by the static load and the von Mises stress distribution is significantly increased to about 150 kPa through the cyclic loading. In total, the results does not only trace the efficacy of an individual 3D model of MSC using biomechanical experiments of cell modulation, but these results provide knowledge in interpretations from cell geometry. The current study was performed to determine a realistic aspect of cell behavior. - Graphical abstract: Based on confocal microscopy images and through finite elements analysis, we simulate mechanical behavior of the stem cell components (the cell membrane, cytoplasm and nucleus) under a compressive load. A major novelty of this investigation is the usage of viscohyperelastic behavior for the realistic stem

Pedagogical Factors Stimulating the Self-Development of Students' Multi-Dimensional Thinking in Terms of Subject-Oriented Teaching

Science.gov (United States)

Andreev, Valentin I.

2014-01-01

The main aim of this research is to disclose the essence of students' multi-dimensional thinking, also to reveal the rating of factors which stimulate the raising of effectiveness of self-development of students' multi-dimensional thinking in terms of subject-oriented teaching. Subject-oriented learning is characterized as a type of learning where…

The influence of dibutyryl adenosine cyclic monophosphate on cell proliferation in the epithelium of the jejunal crypts, the colonic crypts and in colonic carcinomata of rat.

Science.gov (United States)

Tutton, P J; Barkla, D H

1980-01-01

1. Cell proliferation in the jejunal crypts, the colonic crypts and in dimethylhydrazine (DMH)-induced adenocarcinomata of rat colon was measured using a stathmokinetic technique. 2. Dibutryl cyclic adneosine monophosphate (dibutyryl cAMP) was found to inhibit cell proliferation in colonic crypts and in colonic adenocarcinomata. 3. Dibutryl cAMP at very high doses was found to inhibit jejunal crypt cell proliferation but at lower doses was found to accelerate jejunal crypt cell proliferation. 4. Neither bilateral adrenalectomy nor chemical sympathectomy was found to abolish the ability of dibutryl cAMP to stimulate jejunal crypt cell proliferation. 5. The present results are difficult to interpret in terms of known hormonal influences on cell proliferation in the tissues examined and of established actions, of these hormones on cyclic nucleotide metabolism in other tissues.

Infinity-Norm Permutation Covering Codes from Cyclic Groups

OpenAIRE

Karni, Ronen; Schwartz, Moshe

2017-01-01

We study covering codes of permutations with the $\\ell_\\infty$-metric. We provide a general code construction, which uses smaller building-block codes. We study cyclic transitive groups as building blocks, determining their exact covering radius, and showing linear-time algorithms for finding a covering codeword. We also bound the covering radius of relabeled cyclic transitive groups under conjugation.

Influence of cyclic torsional preloading on cyclic fatigue resistance of nickel - titanium instruments.

Science.gov (United States)

Pedullà, E; Lo Savio, F; Boninelli, S; Plotino, G; Grande, N M; Rapisarda, E; La Rosa, G

2015-11-01

To evaluate the effect of different torsional preloads on cyclic fatigue resistance of endodontic rotary instruments constructed from conventional nickel-titanium (NiTi), M-Wire or CM-Wire. Eighty new size 25, 0.06 taper Mtwo instruments (Sweden & Martina), size 25, 0.06 taper HyFlex CM (Coltene/Whaledent, Inc) and X2 ProTaper Next (Dentsply Maillefer) were used. The Torque and distortion angles at failure of new instruments (n = 10) were measured, and 0% (n = 10), 25%, 50% and 75% (n = 20) of the mean ultimate torsional strength as preloading condition were applied according to ISO 3630-1 for each brand. The twenty files tested for every extent of preload were subjected to 20 or 40 torsional cycles (n = 10). After torsional preloading, the number of cycles to failure was evaluated in a simulated canal with 60° angle of curvature and 5 mm of radius of curvature. Data were analysed using two-way analysis of variance. The fracture surface of each fragment was examined with a scanning electron microscope (SEM). Data were analysed by two-way analyses of variance. Preload repetitions did not influence the cyclic fatigue of the three brands; however, the 25%, 50% and 75% torsional preloading significantly reduced the fatigue resistance of all instruments tested (P 0.05). Torsional preloads reduced the cyclic fatigue resistance of conventional and treated (M-wire and CM-wire) NiTi rotary instruments except for size 25, 0.06 taper HyFlex CM instruments with a 25% of torsional preloading. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Cyclic plastic response of nickel-based superalloy at room and at elevated temperatures

Czech Academy of Sciences Publication Activity Database

Polák, Jaroslav; Petrenec, Martin; Chlupová, Alice; Tobiáš, Jiří; Petráš, Roman

2015-01-01

Roč. 57, č. 2 (2015), s. 119-125 ISSN 0025-5300 R&D Projects: GA ČR(CZ) GA13-23652S; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081723 Keywords : cyclic plasticity * elevat ed temperature * superalloys * hysteresis loop * statistical theory Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 0.266, year: 2015

Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis

DEFF Research Database (Denmark)

Zohlnhofer, D.; Dibra, A.; Koppara, T.

2008-01-01

OBJECTIVES: The objective of this meta-analysis was to evaluate the effect of stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) on myocardial regeneration on the basis of a synthesis of the data generated by randomized, controlled clinical trials of G-CSF after acute...

Entire cyclic cohomology and modular theory

International Nuclear Information System (INIS)

Stoytchev, O.Ts.

1992-04-01

We display a close relationship between C* and W*-dynamical systems with KMS states on them and entire cyclic cohomology theory. We construct a character form which assigns to each such system (A, α, R) an even entire cyclic cocycle of the subalgebra A of differentiable (with respect to the given automorphism group) elements of A. We argue that the most interesting case is the von Neumann algebra one, where the automorphism group is determined uniquely by the faithful normal state on the algebra (the modular group) and where the character may provide important information about the algebra. (author). 11 refs

A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea

Directory of Open Access Journals (Sweden)

Noelia Campillo

2016-07-01

Full Text Available Intermittent hypoxia (IH, a hallmark of obstructive sleep apnea (OSA, plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS and consists of a cylindrical well covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time 6 s. Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1α (HIF-1α expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch.

Cloning and expression of porcine Colony Stimulating Factor-1 (CSF-1) and Colony Stimulating Factor-1 Receptor (CSF-1R) and analysis of the species specificity of stimulation by CSF-1 and Interleukin 34

Science.gov (United States)

Gow, Deborah J.; Garceau, Valerie; Kapetanovic, Ronan; Sester, David P.; Fici, Greg J.; Shelly, John A.; Wilson, Thomas L.; Hume, David A.

2012-01-01

Macrophage Colony Stimulating Factor (CSF-1) controls the survival, differentiation and proliferation of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, Interleukin 34 (IL-34), has been described, but its physiological role is not yet known. The domestic pig provides an alternative to traditional rodent models for evaluating potential therapeutic applications of CSF-1R agonists and antagonists. To enable such studies, we cloned and expressed active pig CSF-1. To provide a bioassay, pig CSF-1R was expressed in the factor-dependent Ba/F3 cell line. On this transfected cell line, recombinant porcine CSF-1 and human CSF-1 had identical activity. Mouse CSF-1 does not interact with the human CSF-1 receptor but was active on pig. By contrast, porcine CSF-1 was active on mouse, human, cat and dog cells. IL-34 was previously shown to be species-specific, with mouse and human proteins demonstrating limited cross-species activity. The pig CSF-1R was equally responsive to both mouse and human IL-34. Based upon the published crystal structures of CSF-1/CSF-1R and IL34/CSF-1R complexes, we discuss the molecular basis for the species specificity. PMID:22974529

Riboflavin in cyclic vomiting syndrome: efficacy in three children.

Science.gov (United States)

Martinez-Esteve Melnikova, Anastasia; Schäppi, Michela G; Korff, Christian

2016-01-01

Cyclic vomiting syndrome is an episodic disorder considered to be a migraine variant. Riboflavin is efficient in the prophylactic treatment of migraines in adults. We describe the effectiveness and tolerance of riboflavin treatment in three children with cyclic vomiting syndrome. All of them fulfilled the diagnosis criteria for cyclic vomiting syndrome. They received prophylactic monotherapy with riboflavin for at least 12 months. Excellent response and tolerability was observed. Based on clinical observation in three cases, riboflavin may be an effective and safe prophylactic treatment for children with cyclic vomiting syndrome. CVS is one of the "childhood periodic syndromes" classified as a migraine subtype by the International Headache Society. Riboflavin is currently used as a prophylactic treatment in patients with migraine. Riboflavin may be an effective and safe prophylactic treatment for children with CVS. Increasing doses of riboflavin and long periods of prophylaxis may be needed in some children..

Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer

NARCIS (Netherlands)

deGraaf, H; Willemse, PHB; Bong, SB; Piersma, H; Tjabbes, T; vanVeelen, H; Coenen, JLLM; deVries, EGE

1996-01-01

The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF

Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

DEFF Research Database (Denmark)

Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller

2008-01-01

AMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho......-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of c......AMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response....

Anisotropic yield surfaces in bi-axial cyclic plasticity

International Nuclear Information System (INIS)

Rider, R.J.; Harvey, S.J.; Breckell, T.H.

1985-01-01

Some aspects of the behaviour of yield surfaces and work-hardening surfaces occurring in biaxial cyclic plasticity have been studied experimentally and theoretically. The experimental work consisted of subjecting thin-walled tubular steel specimens to cyclic plastic torsion in the presence of sustained axial loads of various magnitudes. The experimental results show that considerable anisotropy is induced when the cyclic shear strains are dominant. Although the true shapes of yield and work-hardening surfaces can be very complex, a mathematical model is presented which includes both anisotropy and Bauschinger effects. The model is able to qualitatively predict the deformation patterns during a cycle of applied plastic shear strain for a range of sustained axial stresses and also indicate the material response to changes in axial stress. (orig.)

Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells

International Nuclear Information System (INIS)

Horiuchi, Rie; Akimoto, Takayuki; Hong, Zhang; Ushida, Takashi

2012-01-01

Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling. -- Highlights: ► The expression of Nanog, which is an essential regulator of “stemness” was reduced during embryonic stem (ES) cell differentiation. ► Cyclic mechanical strain attenuated the reduction of Nanog expression. ► Cyclic mechanical strain promoted PI3K-Akt signaling and mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor and an inhibitor of actin polymerization.

Degradation forecast for PEMFC cathode-catalysts under cyclic loads

Science.gov (United States)

Moein-Jahromi, M.; Kermani, M. J.; Movahed, S.

2017-08-01

Degradation of Fuel Cell (FC) components under cyclic loads is one of the biggest bottlenecks in FC commercialization. In this paper, a novel experimental based algorithm is presented to predict the Catalyst Layer (CL) performance loss during cyclic load. The algorithm consists of two models namely Models 1 and 2. The Model 1 calculates the Electro-Chemical Surface Area (ECSA) and agglomerate size (e.g. agglomerate radius, rt,agg) for the catalyst layer under cyclic load. The Model 2 is the already-existing model from our earlier studies that computes catalyst performance with fixed structural parameters. Combinations of these two Models predict the CL performance under an arbitrary cyclic load. A set of parametric/sensitivity studies is performed to investigate the effects of operating parameters on the percentage of Voltage Degradation Rate (VDR%) with rank 1 for the most influential one. Amongst the considered parameters (such as: temperature, relative humidity, pressure, minimum and maximum voltage of the cyclic load), the results show that temperature and pressure have the most and the least influences on the VDR%, respectively. So that, increase of temperature from 60 °C to 80 °C leads to over 20% VDR intensification, the VDR will also reduce 1.41% by increasing pressure from 2 atm to 4 atm.

Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily.

Science.gov (United States)

Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Franks, Stephen; Hardy, Kate

2017-04-01

Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.

Curcumin attenuates lipolysis stimulated by tumor necrosis factor-α or isoproterenol in 3T3-L1 adipocytes.

Science.gov (United States)

Xie, Xiao-yun; Kong, Po-Ren; Wu, Jin-feng; Li, Ying; Li, Yan-xiang

2012-12-15

Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes. Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation. Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (p<0.05). The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by curcumin (10-20 μM, p<0.05), which was compatible with reduced perilipin phosphorylation(29%, p<0.05) and hormone-sensitive lipase translocation(20%, p<0.05). This study provides evidence that curcumin acts on adipocytes to suppress the lipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity. Copyright © 2012 Elsevier GmbH. All rights reserved.

Proliferation kinetics and cyclic AMP as prognostic factors in adult acute leukemia.

Science.gov (United States)

Paietta, E; Mittermayer, K; Schwarzmeier, J

1980-07-01

In 41 adult patients with acute leukemia (myeloblastic, lymphoblastic, and undifferentiated), proliferation kinetics (as determined by double-label autoradiography) and cyclic adenosine 3',5'-monophosphate (cAMP) concentration were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly shorter turnover times and higher labeling indices in the bone marrow than did those who failed to respond to treatment. Cases for which cell kinetics did not correlate with clinical response were explained by variance in the distribution of leukemic blasts between the proliferative cell cycle and the resting pool. Good clinical response was also found to be associated with low levels of cAMP in leukemic cells prior to therapy, whereas high cAMP contents predicted failure. Low cAMP concentrations, however, did not necessarily correlate with short turnover times and vice versa. This might be due to fluctuations of the cAMP concentrations during the cell cycle.

Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors.

Science.gov (United States)

El-Gamal, Mohammed I; Al-Ameen, Shahad K; Al-Koumi, Dania M; Hamad, Mawadda G; Jalal, Nouran A; Oh, Chang-Hyun

2018-01-17

Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the CSF-1R. Another ligand, interlukin-34 (IL-34), was recently reported to activate the CSF-1R receptor in a different manner. The relationship between CSF-1R and microglia has been reviewed. Both CSF-1 antibodies and small molecule CSF-1R kinase inhibitors have now been tested in animal models and in humans. In this Perspective, we discuss the role of CSF-1 and IL-34 in producing cancer, bone disorders, and inflammation. We also review the newly discovered and improved small molecule kinase inhibitors and monoclonal antibodies that have shown potent activity toward CSF-1R, reported from 2012 until 2017.

Characterization of cyclical phases in the manufacturing industry in Spain

OpenAIRE

Sala, Mercè; Torres, Teresa; Farré, Mariona

2014-01-01

Purpose: The purpose of this paper is to characterize the cyclical phases of the manufacturing industry in Spain and detect which industries have more influence on the Spanish business cycle. We assume that economic growth is a priority; we are going to determine which industries have a more/less appropriate cyclical behavior according this priority. We analyze if the industries with better cyclical behavior are the ones that achieve greater co-movement with the business cycle of the Spanish...

Chronic, percutaneous connector for electrical recording and stimulation with microelectrode arrays.

Science.gov (United States)

Shah, Kedar G; Lee, Kye Young; Tolosa, Vanessa; Tooker, Angela; Felix, Sarah; Benett, William; Pannu, Satinderpall

2014-01-01

The translation of advances in neural stimulation and recording research into clinical practice hinges on the ability to perform chronic experiments in awake and behaving animal models. Advances in microelectrode array technology, most notably flexible polymer arrays, have significantly improved reliability of the neural interface. However, electrical connector technology has lagged and is prone to failure from non-biocompatibility, large size, contamination, corrosion, and difficulty of use. We present a novel chronic, percutaneous electrical connector system that is suitable for neural stimulation and recording. This system features biocompatible materials, low connect and disconnect forces, passive alignment, and a protective cap during non-use. We have successfully designed, assembled, and tested in vitro both a 16-channel system and a high density 64-channel system. Custom, polyimide, 16-channel, microelectrode arrays were electrically assembled with the connector system and tested using cyclic voltammetry and electrochemical impedance spectroscopy. This connector system is versatile and can be used with a variety of microelectrode array technologies for chronic studies.

Cyclic Creep Behavior of Modified 9Cr-1Mo Steel at 600 .deg. C

International Nuclear Information System (INIS)

Kim, Woo Gon; Kim, Dae Whan; Jang, Jin Sung; Park, Jae Young

2012-01-01

Cyclic deformation behavior is important in practice because high-temperature structural components are exposed under the cyclic conditions of repeated loading. In static creep (SC), the response of the material is simple as a static state of monotonic loading. However, in cyclic creep (CC), it is complex as dynamic loading. Cyclic creep data have been rarely reported until now. In particular, it is not understood well whether cyclic creep will accelerate or retard the creep rate compared with static creep, because it is not only the plastic deformation under cyclic loading is drastically different from monotonic loading, but also the cyclic response is dependent on the cycling frequency, stress range, stress ratio, and hold periods of cycling. Therefore, it is necessary to clarify the cyclic creep behavior influencing the creep deformation and fracture process. In this study, a series of cyclic creep tests was carried out using magnitudes of stress range of constant stress ratio (R=0.1) under continuous tension-tension loading cycles at a hold time of 10 minutes. Cyclic curves were monitored and obtained with time variations, and the properties of the cyclic creep tests were compared with those of static creep tests. The fracture microstructures were observed and analyzed

High levels of cyclic-di-GMP in plant-associated Pseudomonas correlate with evasion of plant immunity.

Science.gov (United States)

Pfeilmeier, Sebastian; Saur, Isabel Marie-Luise; Rathjen, John Paul; Zipfel, Cyril; Malone, Jacob George

2016-05-01

The plant innate immune system employs plasma membrane-localized receptors that specifically perceive pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). This induces a defence response called pattern-triggered immunity (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to potential immune recognition and must employ strategies to evade and/or suppress PTI to successfully colonize the plant. During plant infection, the flagellum has an ambiguous role, acting as both a virulence factor and also as a potent immunogen as a result of the recognition of its main building block, flagellin, by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2 (FLS2). Therefore, strict control of flagella synthesis is especially important for plant-associated bacteria. Here, we show that cyclic-di-GMP [bis-(3'-5')-cyclic di-guanosine monophosphate], a central regulator of bacterial lifestyle, is involved in the evasion of PTI. Elevated cyclic-di-GMP levels in the pathogen Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1 and the commensal P. protegens Pf-5 inhibit flagellin synthesis and help the bacteria to evade FLS2-mediated signalling in Nicotiana benthamiana and Arabidopsis thaliana. Despite this, high cellular cyclic-di-GMP concentrations were shown to drastically reduce the virulence of Pto DC3000 during plant infection. We propose that this is a result of reduced flagellar motility and/or additional pleiotropic effects of cyclic-di-GMP signalling on bacterial behaviour. © 2015 THE AUTHORS MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

METHODOLOGICAL ASPECTS OF ECONOMIC EVENTS CYCLICITY METHOD CONSIDERATION

Directory of Open Access Journals (Sweden)

Yaskova Natalia Yur'ievna

2017-07-01

Full Text Available The cyclicity of economic phenomena is not only their immanent property but also the subject of economic analysis. The modern way of making managerial decisions requires analysis of a number of cycles that fill any kind of activity. Accounting and reconciliation of construction, design, investment, purchasing, reproduction, leasing and other cycles is important for the investment and construction sector, both from the point of view of the need for their synchronization and from the position of determining trends in sectoral development. The analysis has showed that three main types of development are characteristic for investment and construction activity. Increasing intensity is inherent in a high level of cyclic synchronization. The degradation trend arises as a result of mismatched cycles. The stabilization character is inherent in the regular modes of maintaining the established proportions and cyclical inter-conformity. The study of the cyclical nature of investment and building processes is impossible without understanding their co-ordination. The principles of synchronization and subordination of the cycles should be used not only for the construction of cost-effective systems but also for the development of management tools.

Cyclic deformation and fatigue behaviors of Hadfield manganese steel

Energy Technology Data Exchange (ETDEWEB)

Kang, J. [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); Zhang, F.C., E-mail: zfc@ysu.edu.cn [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); Long, X.Y. [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004 (China); Lv, B. [School of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004 (China)

2014-01-03

The cyclic deformation characteristics and fatigue behaviors of Hadfield manganese steel have been investigated by means of its ability to memorize strain and stress history. Detailed studies were performed on the strain-controlled low cycle fatigue (LCF) and stress-controlled high cycle fatigue (HCF). Initial cyclic hardening to saturation or peak stress followed by softening to fracture occurred in LCF. Internal stress made the dominant contribution to the fatigue crack propagation until failure. Effective stress evolution revealed the existence of C–Mn clusters with short-range ordering in Hadfield manganese steel and demonstrated that the interaction between C atoms in the C–Mn cluster and dislocation was essential for its cyclic hardening. The developing/developed dislocation cells and stacking faults were the main cyclic deformation microstructures on the fractured sample surface in LCF and HCF, which manifested that fatigue failure behavior of Hadfield manganese steel was induced by plastic deformation during strain-controlled or stress-controlled testing.

The Role of Growth Factors (VEGF, TGF-β1 and Cyclic Guanosine Monophosphate in the Formation of Pulmonary Hypertension in Children with Bronchopulmonary Dysplasia

Directory of Open Access Journals (Sweden)

A.S. Senatorova

2013-10-01

Full Text Available In 82 children with bronchopulmonary dysplasia (from 1 to 36 months of corrected age we investigated the level of VEGF, TGF-β1 in blood and cyclic guanosine monophosphate (cGMP in sputum. It was revealed that children with bronchopulmonary dysplasia had a significant increase in TGF-β1 (p < 0.05 and cGMP (p < 0.01–0.001, reduced VEGF (p < 0.05, indicating inhibition of angiogenesis, activation of fibrosis factors and endothelium-dependent vasodilation. Reliable direct dependence of activation of TGF-β1 in blood and cGMP in sputum, as well as inverse correlation between VEGF in blood and rLA had been proved, which gave reason to think of pulmonary hypertension as an adverse factor in fibrosis activation and angiogenesis inhibition in children with bronchopulmonary dysplasia. Reduced oxygen saturation and oxygen partial pressure moderately activated cGMP, but did not provide a sufficient reduction of pressure in the pulmonary artery.

In vivo cyclic loading as a potent stimulatory signal for bone formation inside tissue engineering scaffold

Directory of Open Access Journals (Sweden)

A Roshan-Ghias

2010-02-01

Full Text Available In clinical situations, bone defects are often located at load bearing sites. Tissue engineering scaffolds are future bone substitutes and hence they will be subjected to mechanical stimulation. The goal of this study was to test if cyclic loading can be used as stimulatory signal for bone formation in a bone scaffold. Poly(L-lactic acid (PLA/ 5% beta-tricalcium phosphate (beta-TCP scaffolds were implanted in both distal femoral epiphyses of eight rats. Right knees were stimulated (10N, 4Hz, 5 min five times, every two days, starting from the third day after surgery while left knees served as control. Finite element study of the in vivo model showed that the strain applied to the scaffold is similar to physiological strains. Using micro-computed tomography (CT, all knees were scanned five times after the surgery and the related bone parameters of the newly formed bone were quantified. Statistical modeling was used to estimate the evolution of these parameters as a function of time and loading. The results showed that mechanical stimulation had two effects on bone volume (BV: an initial decrease in BV at week 2, and a long-term increase in the rate of bone formation by 28%. At week 13, the BV was then significantly higher in the loaded scaffolds.

The Synthesis of Unsubstituted Cyclic Imides Using Hydroxylamine under Microwave Irradiation

Directory of Open Access Journals (Sweden)

Yousef Hijji

2008-01-01

Full Text Available Unsubstituted cyclic imides were synthesized from a series of cyclic anhydrides,hydroxylamine hydrochloride (NH2OH·HCl, and 4-N,N-dimethylamino-pyridine (DMAP,base catalyst under microwave irradiation in monomode and multimode microwaves. Thisnovel microwave synthesis produced high yields of the unsubstituted cyclic imides forboth the monomode (61 - 81% and multimode (84 - 97% microwaves.

Classifying spaces with virtually cyclic stabilizers for linear groups

DEFF Research Database (Denmark)

Degrijse, Dieter Dries; Köhl, Ralf; Petrosyan, Nansen

2015-01-01

We show that every discrete subgroup of GL(n, ℝ) admits a finite-dimensional classifying space with virtually cyclic stabilizers. Applying our methods to SL(3, ℤ), we obtain a four-dimensional classifying space with virtually cyclic stabilizers and a decomposition of the algebraic K-theory of its...

Cyclic GMP-mediated memory enhancement in the object recognition test by inhibitors of phosphodiesterase-2 in mice.

Science.gov (United States)

Lueptow, Lindsay M; Zhan, Chang-Guo; O'Donnell, James M

2016-02-01

Cyclic nucleotide phosphodiesterase-2 (PDE2) is a potential therapeutic target for the treatment of cognitive dysfunction. Using the object recognition test (ORT), this study assessed the effects of two PDE2 inhibitors, Bay 60-7550 and ND7001, on learning and memory, and examined underlying mechanisms. To assess the role of PDE2 inhibition on phases of memory, Bay 60-7550 (3 mg/kg) was administered: 30 min prior to training; 0, 1, or 3 h after training; or 30 min prior to recall testing. To assess cyclic nucleotide involvement in PDE2 inhibitor-enhanced memory consolidation, either the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg; intraperitoneal (IP)), soluble guanylyl cyclase inhibitor 1H-[-1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 20 mg/kg; IP), protein kinase G inhibitor KT5823 (2.5 μg; intracerebroventricular (ICV)), or protein kinase A inhibitor H89 (1 μg; ICV) was administered 30 min prior to the PDE2 inhibitor Bay 60-7550 (3 mg/kg) or ND7001 (3 mg/kg). Changes in the phosphorylation of 3'5'-cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) at Ser-133 and vasodilator-stimulated phosphoprotein (VASP) at Ser-239 were determined to confirm activation of cAMP and 3'5'-cyclic guanosine monophosphate (cGMP) signaling. Bay 60-7550 (3 mg/kg) enhanced memory of mice in the ORT when given 30 min prior to training, immediately after training, or 30 min prior to recall. Inhibitors of the cGMP pathway blocked the memory-enhancing effects of both Bay 60-7550 (3 mg/kg) and ND7001 (3 mg/kg) on early consolidation processes. Bay 60-7550 (3 mg/kg) enhanced phosphorylation of CREB and VASP, both targets of cGMP-dependent protein kinase (PKG). These results confirm a potential of PDE2, or components of its signaling pathway, as a therapeutic target for drug discovery focused on restoring memory function.

Constitutive model and electroplastic analysis of structures under cyclic loading

International Nuclear Information System (INIS)

Wang, X.; Lei, Y; Du, Q.

1989-01-01

Many engineering structures in nuclear reactors, thermal power stations, chemical plants and aerospace vehicles are subjected to cyclic mechanic-thermal loading, which is the main cause of structural fatigue failure. Over the past twenty years, designers and researchers have paid great attention to the research on life prediction and elastoplastic analysis of structures under cyclic loading. One of the key problems in elastoplastic analysis is to construct a reasonable constitutive model for cyclic plasticity. In the paper, the constitutive equations are briefly outlined. Then, the model is implemented in a finite element code to predict the response of cyclic loaded structural components such as a double-edge-notched plate, a grooved bar and a nozzle in spherical shell. Numerical results are compared with those from other theories and experiments

Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice.

Science.gov (United States)

Park, Dong-Wook; Ness, Jared P; Brodnick, Sarah K; Esquibel, Corinne; Novello, Joseph; Atry, Farid; Baek, Dong-Hyun; Kim, Hyungsoo; Bong, Jihye; Swanson, Kyle I; Suminski, Aaron J; Otto, Kevin J; Pashaie, Ramin; Williams, Justin C; Ma, Zhenqiang

2018-01-23

Electrical stimulation using implantable electrodes is widely used to treat various neuronal disorders such as Parkinson's disease and epilepsy and is a widely used research tool in neuroscience studies. However, to date, devices that help better understand the mechanisms of electrical stimulation in neural tissues have been limited to opaque neural electrodes. Imaging spatiotemporal neural responses to electrical stimulation with minimal artifact could allow for various studies that are impossible with existing opaque electrodes. Here, we demonstrate electrical brain stimulation and simultaneous optical monitoring of the underlying neural tissues using carbon-based, fully transparent graphene electrodes implanted in GCaMP6f mice. Fluorescence imaging of neural activity for varying electrical stimulation parameters was conducted with minimal image artifact through transparent graphene electrodes. In addition, full-field imaging of electrical stimulation verified more efficient neural activation with cathode leading stimulation compared to anode leading stimulation. We have characterized the charge density limitation of capacitive four-layer graphene electrodes as 116.07-174.10 μC/cm 2 based on electrochemical impedance spectroscopy, cyclic voltammetry, failure bench testing, and in vivo testing. This study demonstrates the transparent ability of graphene neural electrodes and provides a method to further increase understanding and potentially improve therapeutic electrical stimulation in the central and peripheral nervous systems.

Modeling Cyclic Variation of Intracranial Pressure

National Research Council Canada - National Science Library

Daley, M

2001-01-01

...) recording during mechanical ventilation are due to cyclic extravascular compressional modulation primarily of the cerebral venous bed, an established isovolumetric model of cerebrospinal fluid...

Prognosis of Cyclic Vomiting Syndrome

Directory of Open Access Journals (Sweden)

J. Gordon Millichap

2016-03-01

Full Text Available Investigators from Teikyo University School of Medicine, Tokyo, Japan, evaluated the clinical features, prognosis, and prophylaxis of cyclic vomiting syndrome and the relationship between the syndrome and levels of adrenocorticotropic/antidiuretic hormones (ACTH/ADH.

Existence and Convergence of Best Proximity Points for Semi Cyclic Contraction Pairs

Directory of Open Access Journals (Sweden)

Balwant Singh Thakur

2014-02-01

Full Text Available In this article, we introduce the notion of a semi cyclic ϕ-contraction pair of mappings, which contains semi cyclic contraction pairs as a subclass. Existence and convergence results of best proximity points for semi cyclic ϕ- contraction pair of mappings are obtained.

A Practical Beginner's Guide to Cyclic Voltammetry

Science.gov (United States)

Elgrishi, Noémie; Rountree, Kelley J.; McCarthy, Brian D.; Rountree, Eric S.; Eisenhart, Thomas T.; Dempsey, Jillian L.

2018-01-01

Despite the growing popularity of cyclic voltammetry, many students do not receive formalized training in this technique as part of their coursework. Confronted with self-instruction, students can be left wondering where to start. Here, a short introduction to cyclic voltammetry is provided to help the reader with data acquisition and…

Biosynthesis of cyclic 2,3-diphosphoglycerate. Isolation and characterization of 2-phosphoglycerate kinase and cyclic 2,3-diphosphoglycerate synthetase from Methanothermus fervidus.

Science.gov (United States)

Lehmacher, A; Vogt, A B; Hensel, R

1990-10-15

Starting from 2-phosphoglycerate the biosynthesis of cDPG comprises two steps: (i) the phosphorylation of 2-phosphoglycerate to 2,3-diphosphoglycerate and (ii) the intramolecular cyclization to cyclic 2,3-diphosphoglycerate. The involved enzymes, 2-phosphoglycerate kinase and cyclic 2,3-diphosphoglycerate synthetase, were purified form Methanothermus fervidus. Their molecular and catalytic properties were characterized.

An electromagnetic compressive force by cell exciter stimulates chondrogenic differentiation of bone marrow-derived mesenchymal stem cells.

Science.gov (United States)

Park, Sang-Hyug; Sim, Woo Young; Park, Sin Wook; Yang, Sang Sik; Choi, Byung Hyune; Park, So Ra; Park, Kwideok; Min, Byoung-Hyun

2006-11-01

In this study, we present a biological micro-electromechanical system and its application to the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (MSCs). Actuated by an electromagnetic force, the micro cell exciter was designed to deliver a cyclic compressive load (CCL) with various magnitudes. Two major parts in the system are an actuator and a cartridge-type chamber. The former has a permanent magnet and coil, and the latter is equipped with 7 sample dishes and 7 metal caps. Mixed with a 2.4% alginate solution, the alginate/MSC layers were positioned in the sample dishes; the caps contained chondrogenic defined medium without transforming growth factor-beta (TGF-beta). Once powered, the actuator coil-derived electromagnetic force pulled the metal caps down, compressing the samples. The cyclic load was given at 1-Hz frequency for 10 min twice a day. Samples in the dishes without a cap served as a control. The samples were analyzed at 3, 5, and 7 days after stimulation for cell viability, biochemical assays, histologic features, immunohistochemistry, and gene expression of the chondrogenic markers. Applied to the alginate/MSC layer, the CCL system enhanced the synthesis of cartilage-specific matrix proteins and the chondrogenic markers, such as aggrecan, type II collagen, and Sox9. We found that the micromechanically exerted CCL by the cell exciter was very effective in enhancing the chondrogenic differentiation of MSCs, even without using exogenous TGF-beta.

Topological chaos, braiding and bifurcation of almost-cyclic sets.

Science.gov (United States)

Grover, Piyush; Ross, Shane D; Stremler, Mark A; Kumar, Pankaj

2012-12-01

In certain two-dimensional time-dependent flows, the braiding of periodic orbits provides a way to analyze chaos in the system through application of the Thurston-Nielsen classification theorem (TNCT). We expand upon earlier work that introduced the application of the TNCT to braiding of almost-cyclic sets, which are individual components of almost-invariant sets [Stremler et al., "Topological chaos and periodic braiding of almost-cyclic sets," Phys. Rev. Lett. 106, 114101 (2011)]. In this context, almost-cyclic sets are periodic regions in the flow with high local residence time that act as stirrers or "ghost rods" around which the surrounding fluid appears to be stretched and folded. In the present work, we discuss the bifurcation of the almost-cyclic sets as a system parameter is varied, which results in a sequence of topologically distinct braids. We show that, for Stokes' flow in a lid-driven cavity, these various braids give good lower bounds on the topological entropy over the respective parameter regimes in which they exist. We make the case that a topological analysis based on spatiotemporal braiding of almost-cyclic sets can be used for analyzing chaos in fluid flows. Hence, we further develop a connection between set-oriented statistical methods and topological methods, which promises to be an important analysis tool in the study of complex systems.

Micromechanics of soil responses in cyclic simple shear tests

Directory of Open Access Journals (Sweden)

Cui Liang

2017-01-01

Full Text Available Offshore wind turbine (OWT foundations are subjected to a combination of cyclic and dynamic loading arising from wind, wave, rotor and blade shadowing. Under cyclic loading, most soils change their characteristics including stiffness, which may cause the system natural frequency to approach the loading frequency and lead to unplanned resonance and system damage or even collapse. To investigate such changes and the underlying micromechanics, a series of cyclic simple shear tests were performed on the RedHill 110 sand with different shear strain amplitudes, vertical stresses and initial relative densities of soil. The test results showed that: (a Vertical accumulated strain is proportional to the shear strain amplitude but inversely proportional to relative density of soil; (b Shear modulus increases rapidly in the initial loading cycles and then the rate of increase diminishes and the shear modulus remains below an asymptote; (c Shear modulus increases with increasing vertical stress and relative density, but decreasing with increasing strain amplitude. Coupled DEM simulations were performed using PFC2D to analyse the micromechanics underlying the cyclic behaviour of soils. Micromechanical parameters (e.g. fabric tensor, coordination number were examined to explore the reasons for the various cyclic responses to different shear strain amplitudes or vertical stresses. Both coordination number and magnitude of fabric anisotropy contribute to the increasing shear modulus.

Chairside CAD/CAM materials. Part 3: Cyclic fatigue parameters and lifetime predictions.

Science.gov (United States)

Wendler, Michael; Belli, Renan; Valladares, Diana; Petschelt, Anselm; Lohbauer, Ulrich

2018-06-01

Chemical and mechanical degradation play a key role on the lifetime of dental restorative materials. Therefore, prediction of their long-term performance in the oral environment should base on fatigue, rather than inert strength data, as commonly observed in the dental material's field. The objective of the present study was to provide mechanistic fatigue parameters of current dental CAD/CAM materials under cyclic biaxial flexure and assess their suitability in predicting clinical fracture behaviors. Eight CAD/CAM materials, including polycrystalline zirconia (IPS e.max ZirCAD), reinforced glasses (Vitablocs Mark II, IPS Empress CAD), glass-ceramics (IPS e.max CAD, Suprinity PC, Celtra Duo), as well as hybrid materials (Enamic, Lava Ultimate) were evaluated. Rectangular plates (12×12×1.2mm 3 ) with highly polished surfaces were prepared and tested in biaxial cyclic fatigue in water until fracture using the Ball-on-Three-Balls (B3B) test. Cyclic fatigue parameters n and A* were obtained from the lifetime data for each material and further used to build SPT diagrams. The latter were used to compare in-vitro with in-vivo fracture distributions for IPS e.max CAD and IPS Empress CAD. Susceptibility to subcritical crack growth under cyclic loading was observed for all materials, being more severe (n≤20) in lithium-based glass-ceramics and Vitablocs Mark II. Strength degradations of 40% up to 60% were predicted after only 1 year of service. Threshold stress intensity factors (K th ) representing the onset of subcritical crack growth (SCG), were estimated to lie in the range of 0.37-0.44 of K Ic for the lithium-based glass-ceramics and Vitablocs Mark II and between 0.51-0.59 of K Ic for the other materials. Failure distributions associated with mechanistic estimations of strength degradation in-vitro showed to be useful in interpreting failure behavior in-vivo. The parameter K th stood out as a better predictor of clinical performance in detriment to the SCG n

Constraining cyclic peptides to mimic protein structure motifs

DEFF Research Database (Denmark)

Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik

2014-01-01

peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides...... and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic pepti-domimetics that refine peptide structure and confer biological properties....

Increased macrophage colony-stimulating factor levels in patients with Graves' disease.

Science.gov (United States)

Morishita, Eriko; Sekiya, Akiko; Hayashi, Tomoe; Kadohira, Yasuko; Maekawa, Mio; Yamazaki, Masahide; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2008-10-01

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves' disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P production of M-CSF in patients with GD.

The Cyclic Stress-Strain Curve of Polycrystals

DEFF Research Database (Denmark)

Pedersen, Ole Bøcker; Rasmussen, K. V.; Winter, A. T.

1982-01-01

The internal stresses implied by the Sachs model are estimated for individual PSBs at low plastic strain amplitudes and for homogeneously sheared grains at higher plastic strain amplitudes. The analysis shows that the Sachs model can account semi-quantitatively for experimentally measured cyclic...... stress-strain curves for copper. A similar approximative analysis of the Taylor model cannot account for the data. An interesting feature of the Sachs model is that, although it is assumed that the flow condition is entirely controlled by the PSBs. the predicted cyclic stress-strain curve displays...

Ekpyrotic and cyclic cosmology

International Nuclear Information System (INIS)

Lehners, Jean-Luc

2008-01-01

Ekpyrotic and cyclic cosmologies provide theories of the very early and of the very late universe. In these models, the big bang is described as a collision of branes - and thus the big bang is not the beginning of time. Before the big bang, there is an ekpyrotic phase with equation of state w=P/(ρ) >>1 (where P is the average pressure and ρ the average energy density) during which the universe slowly contracts. This phase resolves the standard cosmological puzzles and generates a nearly scale-invariant spectrum of cosmological perturbations containing a significant non-Gaussian component. At the same time it produces small-amplitude gravitational waves with a blue spectrum. The dark energy dominating the present-day cosmological evolution is reinterpreted as a small attractive force between our brane and a parallel one. This force eventually induces a new ekpyrotic phase and a new brane collision, leading to the idea of a cyclic universe. This review discusses the detailed properties of these models, their embedding in M-theory and their viability, with an emphasis on open issues and observational signatures

Paresthesia-Independence: An Assessment of Technical Factors Related to 10 kHz Paresthesia-Free Spinal Cord Stimulation.

Science.gov (United States)

De Carolis, Giuliano; Paroli, Mery; Tollapi, Lara; Doust, Matthew W; Burgher, Abram H; Yu, Cong; Yang, Thomas; Morgan, Donna M; Amirdelfan, Kasra; Kapural, Leonardo; Sitzman, B Todd; Bundschu, Richard; Vallejo, Ricardo; Benyamin, Ramsin M; Yearwood, Thomas L; Gliner, Bradford E; Powell, Ashley A; Bradley, Kerry

2017-05-01

Spinal cord stimulation (SCS) has been successfully used to treat chronic intractable pain for over 40 years. Successful clinical application of SCS is presumed to be generally dependent on maximizing paresthesia-pain overlap; critical to achieving this is positioning of the stimulation field at the physiologic midline. Recently, the necessity of paresthesia for achieving effective relief in SCS has been challenged by the introduction of 10 kHz paresthesia-free stimulation. In a large, prospective, randomized controlled pivotal trial, HF10 therapy was demonstrated to be statistically and clinically superior to paresthesia-based SCS in the treatment of severe chronic low back and leg pain. HF10 therapy, unlike traditional paresthesia-based SCS, requires no paresthesia to be experienced by the patient, nor does it require paresthesia mapping at any point during lead implant or post-operative programming. To determine if pain relief was related to technical factors of paresthesia, we measured and analyzed the paresthesia responses of patients successfully using HF10 therapy. Prospective, multicenter, non-randomized, non-controlled interventional study. Outpatient pain clinic at 10 centers across the US and Italy. Patients with both back and leg pain already implanted with an HF10 therapy device for up to 24 months were included in this multicenter study. Patients provided pain scores prior to and after using HF10 therapy. Each patient's most efficacious HF10 therapy stimulation program was temporarily modified to a low frequency (LF; 60 Hz), wide pulse width (~470 mus), paresthesia-generating program. On a human body diagram, patients drew the locations of their chronic intractable pain and, with the modified program activated, all regions where they experienced LF paresthesia. Paresthesia and pain drawings were then analyzed to estimate the correlation of pain relief outcomes to overlap of pain by paresthesia, and the mediolateral distribution of paresthesia (as a

The effects of irradiation on the cytosol glucocorticoid receptor and concentrations of corticosterone and cyclic nucleotides in the rat liver

International Nuclear Information System (INIS)

Teshima, Teruki; Mori, Masaki; Honke, Yoshifumi

1983-01-01

The effects of irradiation on both the cytosol glucocorticoid receptor and concentrations of corticosterone and cyclic nucleotides in the rat liver were investigated. The liver concentrations of corticosterone and cyclic nucleotides were measured by radioimmunoassay before and after the irradiation of 1,000 rad/l fraction. The glucocorticoid receptor in the liver cytosol was determined by the measurement of the cytosol binding to 3 H-dexamethasone. The cytosol and nuclear corticosterone levels reached a peak 1 day after the irradiation of the rat liver and declined to the control levels after 2 days. The increase in corticosterone levels may be due to the direct stimulation of the right adrenal gland and/ or the stress induced by the irradiation. The binding capacity of the glucocorticoid receptor in rat liver cytosol decreased to the minimum 1 day after the irradiation, and the recovery occurred at 4 days. The Kd value of the glucocorticoid receptor remained unchanged from 1 hour until 4 days but was high at 4 and 7 days. The distinctly increased levels of cyclic GMP in the rat liver were found from 1 hour through 7 days after the irradiation, while cyclic AMP did not change. The inversed relationship between the cytosol glucocorticoid receptor and corticosterone levels in cytosol and the nuclei indicates that the receptor-bound corticosterone in cytosol can be transferred to a nucleus and remain there in the presence of appropriate amounts of corticosterone in cytosol, after which the receptor is released from the nucleus into cytosol. The high Kd values observed 4 -- 7 days after the irradiation may be either due to the direct effect of irradiation or to the replenishment of the receptor with a low affinity. (author)

Cyclic mechanical strain maintains Nanog expression through PI3K/Akt signaling in mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Horiuchi, Rie [Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Akimoto, Takayuki, E-mail: akimoto@m.u-tokyo.ac.jp [Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Waseda-tsurumaki, Shinjuku, Tokyo 162-0041 (Japan); Hong, Zhang [Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Waseda-tsurumaki, Shinjuku, Tokyo 162-0041 (Japan); Ushida, Takashi [Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan)

2012-08-15

Mechanical strain has been reported to affect the proliferation/differentiation of many cell types; however, the effects of mechanotransduction on self-renewal as well as pluripotency of embryonic stem (ES) cells remains unknown. To investigate the effects of mechanical strain on mouse ES cell fate, we examined the expression of Nanog, which is an essential regulator of self-renewal and pluripotency as well as Nanog-associated intracellular signaling during uniaxial cyclic mechanical strain. The mouse ES cell line, CCE was plated onto elastic membranes, and we applied 10% strain at 0.17 Hz. The expression of Nanog was reduced during ES cell differentiation in response to the withdrawal of leukemia inhibitory factor (LIF); however, two days of cyclic mechanical strain attenuated this reduction of Nanog expression. On the other hand, the cyclic mechanical strain promoted PI3K-Akt signaling, which is reported as an upstream of Nanog transcription. The cyclic mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor wortmannin. Furthermore, cytochalasin D, an inhibitor of actin polymerization, also inhibited the mechanical strain-induced increase in phospho-Akt. These findings imply that mechanical force plays a role in regulating Nanog expression in ES cells through the actin cytoskeleton-PI3K-Akt signaling. -- Highlights: Black-Right-Pointing-Pointer The expression of Nanog, which is an essential regulator of 'stemness' was reduced during embryonic stem (ES) cell differentiation. Black-Right-Pointing-Pointer Cyclic mechanical strain attenuated the reduction of Nanog expression. Black-Right-Pointing-Pointer Cyclic mechanical strain promoted PI3K-Akt signaling and mechanical strain-induced Akt phosphorylation was blunted by the PI3K inhibitor and an inhibitor of actin polymerization.

Stimulation of phagocytosis by sulforaphane

International Nuclear Information System (INIS)

Suganuma, Hiroyuki; Fahey, Jed W.; Bryan, Kelley E.; Healy, Zachary R.; Talalay, Paul

2011-01-01

Research highlights: → Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. → This effect does not require Nrf2-dependent induction of phase 2 genes. → Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-μm diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2 -/- mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

Stimulation of phagocytosis by sulforaphane

Energy Technology Data Exchange (ETDEWEB)

Suganuma, Hiroyuki, E-mail: hsuganu1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Fahey, Jed W., E-mail: jfahey@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Bryan, Kelley E., E-mail: kbryanm1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Healy, Zachary R., E-mail: zhealy1@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States); Talalay, Paul, E-mail: ptalalay@jhmi.edu [Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205 (United States)

2011-02-04

Research highlights: {yields} Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. {yields} This effect does not require Nrf2-dependent induction of phase 2 genes. {yields} Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-{mu}m diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2{sup -/-} mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

Protective, restorative, and therapeutic properties of recombinant colony-stimulating factors

International Nuclear Information System (INIS)

Talmadge, J.E.; Tribble, H.; Pennington, R.; Bowersox, O.; Schneider, M.A.; Castelli, P.; Black, P.L.; Abe, F.

1989-01-01

Pretreatment of mice with recombinant murine (rM) colony-stimulating factor-granulocyte-macrophage (CSF-gm) or recombinant human (rH) CSF-g provides partial protection from the lethal effects of ionizing radiation or the alkylating agent cyclophosphamide (CTX). In addition, these agents can significantly prolong survival if administered following lethal doses of irradiation or CTX. To induce protective activity, cytokines were injected 20 hours before lethal irradiation or CTX administration. To accelerate recovery from lethal irradiation, the cytokines must be administered shortly following irradiation, and the induction of maximal levels of activity is dependent on chronic administration. In contrast, because of their longer half-lives, accelerated recovery from alkylating agents requires a delay of at least 24 to 48 hours to allow complete clearance of CTX before administration of a CSF. Studies quantitating peripheral blood leukocytes and bone marrow cellularity as well as colony-forming units per culture (CFU-C) frequency and CFU-C per femur revealed a significant correlation between these parameters and the ability to survive lethal irradiation

Is the Fiscal Policy of the Czech Republic Pro-cyclical?

Directory of Open Access Journals (Sweden)

Martin Rolák

2015-01-01

Full Text Available The main goal of this paper is to analyse whether the fiscal policy of the Czech Republic is anti-cyclical. This analysis is carried out through decomposing the government’s balance into its cyclical and structural part. The first differences of the structural part are then put in relation to the output gap to determine whether the fiscal policy is pro- or anti-cyclical. Moreover, the correlation of government expenditures and revenues with the business cycle is also subject of our analysis. We also examine whether the fiscal rules which the Czech Republic would have to adhere to once it enters the euro area limit fiscal policy as a stabilizing mechanism.The paper concludes that the fiscal policy in the Czech Republic was for the most part rather of a random character than anti-cyclical during the examined period 1998–2013. This conclusion has two implications. Firstly, there is still room for improvement in fully and consistently utilizing fiscal policy to stabilise the Czech economy throughout economic cycles. Secondly, fiscal rules would not limit the Czech government to practice anti-cyclical fiscal policy if they have been implemented since 1998.

Cyclic compressive creep-elastoplastic behaviors of in situ TiB_2/Al-reinforced composite

International Nuclear Information System (INIS)

Zhang, Qing; Zhang, Weizheng; Liu, Youyi; Guo, BingBin

2016-01-01

This paper presents a study on the cyclic compressive creep-elastoplastic behaviors of a TiB_2-reinforced aluminum matrix composite (ZL109) at 350 °C and 200 °C. According to the experimental results, under cyclic elastoplasticity and cyclic coupled compressive creep-elastoplasticity, the coupled creep will cause changes in isotropic stress and kinematic stress. Isotropic stress decreases with coupled creep, leading to cyclic softening. Positive kinematic stress, however, increases with coupled creep, leading to cyclic hardening. Transmission electron microscopy (TEM) observations of samples under cyclic compressive creep-elastoplasticity with different temperatures and strain amplitudes indicate that more coupled creep contributes to more subgrain boundaries but fewer intracrystalline dislocations. Based on the macro tests and micro observations, the micro mechanism of compressive creep's influence on cyclic elastoplasticity is elucidated. Dislocations recovering with coupled creep leads to isotropic softening, whereas subgrain structures created by coupled creep lead to kinematic hardening during cyclic deformation.

A Note on the G-Cyclic Operators over a Bounded Semigroup

International Nuclear Information System (INIS)

Hamada, Nuha H.; Jamil, Zeana Z.

2010-08-01

Let H be an infinite-dimensional separable complex Hilbert space, and B(H) be the Banach algebra of all linear bounded operators on H. Let S be a multiplication semigroup of C with 1, an operator T element of B(H) is called G-cyclic operator over S if there is a vector x in H such that {αT n x|α element of S, n ≥ 0} is dense in H. In this case x is called a G-cyclic vector for T over S. If T is G-cyclic operator and S = {1} then T is a hypercyclic operator. In this paper, we study the spectral properties of a G-cyclic operators over a bounded S under the condition that zero is not in the closure of S. We show that the class of all G-cyclic operators is contained in the norm-closure of the class of all hypercyclic operators. (author)

Quantum Codes From Cyclic Codes Over The Ring R 2

International Nuclear Information System (INIS)

Altinel, Alev; Güzeltepe, Murat

2016-01-01

Let R 2 denotes the ring F 2 + μF 2 + υ 2 + μυ F 2 + wF 2 + μwF 2 + υwF 2 + μυwF 2 . In this study, we construct quantum codes from cyclic codes over the ring R 2 , for arbitrary length n, with the restrictions μ 2 = 0, υ 2 = 0, w 2 = 0, μυ = υμ, μw = wμ, υw = wυ and μ (υw) = (μυ) w. Also, we give a necessary and sufficient condition for cyclic codes over R 2 that contains its dual. As a final point, we obtain the parameters of quantum error-correcting codes from cyclic codes over R 2 and we give an example of quantum error-correcting codes form cyclic codes over R 2 . (paper)

Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

Science.gov (United States)

Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

2016-01-01

Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

Separation of isotopes by cyclical processes

International Nuclear Information System (INIS)

Hamrin, C.E. Jr.; Weaver, K.

1976-01-01

Various isotopes of hydrogen are separated by a cyclic sorption process in which a gas stream containing the isotopes is periodically passed through a high pressure column containing a palladium sorbent. A portion of the product from the high pressure column is passed through a second column at lower pressure to act as a purge. Before the sorbent in the high pressure column becomes saturated, the sequence is reversed with the stream flowing through the former low-pressure column now at high pressure, and a portion of the product purging the former high pressure column now at low pressure. The sequence is continued in cyclic manner with the product being enriched in a particular isotope

Cyclic operation of power plant; Cyklisk drift av kraftvaermeverk

Energy Technology Data Exchange (ETDEWEB)

Storesund, Jan

2007-12-15

The great majority of power plants are designed for base load operation with a relatively small number of starts and stops per year. Therefore, there has been no need to consider fatigue at design. Over the last few years operation with more frequent starts and stops exists as a consequence of swinging electricity prices that has become common. This involves significantly higher frequency of damages; not least fatigue relates damages, and the number of severe failures in components that never before have had damage problems may increase as well. In the present work the different types of component that may suffer from cyclic operation related damage are gathered by a literature survey and described as follows: - where and how the damages comes up, - constructions that should be avoided, - non-destructive testing (NDT) for damage that may come up under cyclic operation, - calculation and assessment of integrity of critical components - areas where continued research would be valuable. Recommendations have been put together to be used to prevent cyclic operation related damage and to detect it in time. The target group for this study is i) plant owners of plants where cyclic operation is or may be present, ii) researchers in the area, and, iii) inspectors and NDT-operators. There are quite a number of components where cyclic operation has been found to significantly influence the lift time. Some of these components are described in many papers whereas occasional papers have been found for others. The amount of information that is possible to get for a certain component is likely related to its significance for cyclic operation damage. The most frequently reported problem is ligament cracking of high temperature headers. Other components where extensive studies have been done are: wall panels, creep-fatigue loaded welds and turbine components

Identification of key factors in Accelerated Low Water Corrosion through experimental simulation of tidal conditions: influence of stimulated indigenous microbiota

NARCIS (Netherlands)

Marty, F.; Gueuné, H.; Malard, E.; Sánchez-Amaya, J.M.; Sjögren, L.; Abbas, B.; Quillet, L.; van Loosdrecht, M.C.M.; Muyzer, G.

2014-01-01

Biotic and abiotic factors favoring Accelerated Low Water Corrosion (ALWC) on harbor steel structures remain unclear warranting their study under controlled experimental tidal conditions. Initial stimulation of marine microbial consortia by a pulse of organic matter resulted in localized corrosion

Recent progress on weight distributions of cyclic codes over finite fields

Directory of Open Access Journals (Sweden)

Hai Q. Dinh

2015-01-01

Full Text Available Cyclic codes are an interesting type of linear codes and have wide applications in communication and storage systems due to their efficient encoding and decoding algorithms. In coding theory it is often desirable to know the weight distribution of a cyclic code to estimate the error correcting capability and error probability. In this paper, we present the recent progress on the weight distributions of cyclic codes over finite fields, which had been determined by exponential sums. The cyclic codes with few weights which are very useful are discussed and their existence conditions are listed. Furthermore, we discuss the more general case of constacyclic codes and give some equivalences to characterize their weight distributions.

Cyclic peptides as potential therapeutic agents for skin disorders.

Science.gov (United States)

Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

Heparin-Binding EGF-like Growth Factor (HB-EGF) stimulates the proliferation of Müller glia-derived progenitor cells in avian and murine retinas

Science.gov (United States)

Todd, Levi; Volkov, Leo I.; Zelinka, Chris; Squires, Natalie; Fischer, Andy J.

2015-01-01

Müller glia can be stimulated to de-differentiate, proliferate and form Müller glia-derived progenitor cells (MGPCs) that regenerate retinal neurons. In the zebrafish retina, Heparin-Binding EGF-like Growth Factor (HB-EGF) may be one of the key factors that stimulate the formation of proliferating MGPCs. Currently nothing is known about the influence of HB-EGF on the proliferative potential of Müller glia in retinas of birds and rodents. In the chick retina, we found that levels of both hb-egf and egf-receptor are rapidly and transiently up-regulated following NMDA-induced damage. Although intraocular injections of HB-EGF failed to stimulate cell-signaling or proliferation of Müller glia in normal retinas, HB-EGF stimulated proliferation of MGPCs in damaged retinas. By comparison, inhibition of the EGF-receptor (EGFR) decreased the proliferation of MGPCs in damaged retinas. HB-EGF failed to act synergistically with FGF2 to stimulate the formation of MGPCs in the undamaged retina and inhibition of EGF-receptor did not suppress FGF2-mediated formation of MGPCs. In the mouse retina, HB-EGF stimulated the proliferation of Müller glia following NMDA-induced damage. Furthermore, HB-EGF stimulated not only MAPK-signaling in Müller glia/MGPCs, but also activated mTor- and Jak/Stat-signaling. We propose that levels of expression of EGFR are rate-limiting to the responses of Müller glia to HB-EGF and the expression of EGFR can be induced by retinal damage, but not by FGF2-treatment. We conclude that HB-EGF is mitogenic to Müller glia in both chick and mouse retinas, and HB-EGF is an important player in the formation of MGPCs in damaged retinas. PMID:26500021

Macrophage colony-stimulating factor induces prolactin expression in rat pituitary gland.

Science.gov (United States)

Hoshino, Satoya; Kurotani, Reiko; Miyano, Yuki; Sakahara, Satoshi; Koike, Kanako; Maruyama, Minoru; Ishikawa, Fumio; Sakatai, Ichiro; Abe, Hiroyuki; Sakai, Takafumi

2014-06-01

We investigated the role of macrophage colony-stimulating factor (M-CSF) in the pituitary gland to understand the effect of M-CSF on pituitary hormones and the relationship between the endocrine and immune systems. When we attempted to establish pituitary cell lines from a thyrotropic pituitary tumor (TtT), a macrophage cell line, TtT/M-87, was established. We evaluated M-CSF-like activity in conditioned media (CM) from seven pituitary cell lines using TtT/M-87 cells. TtT/M-87 proliferation significantly increased in the presence of CM from TtT/GF cells, a pituitary folliculostellate (FS) cell line. M-CSF mRNA was detected in TtT/GF and MtT/E cells by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression in TtT/GF cells was increased in a lipopolysaccharide (LPS) dose-dependent manner. M-CSF mRNA expression was also increased in rat anterior pituitary glands by LPS. M-CSF receptor (M-CSFR) mRNA was only detected in TtT/ M-87 cells and increased in the LPS-stimulated rat pituitary glands. In rat pituitary glands, M-CSF and M-CSFR were found to be localized in FS cells and prolactin (PRL)-secreting cells, respectively, by immunohistochemistry. The PRL concentration in rat sera was significantly increased at 24 h after M-CSF administration, and mRNA levels significantly increased in primary culture cells of rat anterior pituitary glands. In addition, TNF-α mRNA was increased in the primary culture cells by M-CSF. These results revealed that M-CSF was secreted from FS cells and M-CSF regulated PRL expression in rat pituitary glands.

Response of monopiles under cyclic lateral loading in sand

DEFF Research Database (Denmark)

Nicolai, Giulio; Ibsen, Lars Bo

2015-01-01

Currently the main design guidelines propose to reduce the lateral resistance of offshore piles when accounting for cyclic loading. The present work provides results from laboratory tests in which such reduction has not occurred. The experimental investigation is based on testing a small......-scale monopile model in dense saturated sand. The experimental setup used to carry out the laboratory tests is able to apply thousands of load cycles and static loading to the monopile model. The purpose of the laboratory tests is to investigate the effects of cyclic loading on the lateral resistance...... of the monopile. It is shown that the soil-pile system becomes stiffer and more resistant after applying cyclic loading, depending on the number of cycles....

Morphogenetic Mechanisms in the Cyclic Regeneration of Hair Follicles and Deer Antlers from Stem Cells

Science.gov (United States)

Li, Chunyi; McMahon, Chris

2013-01-01

We have made comparisons between hair follicles (HFs) and antler units (AUs)—two seemingly unrelated mammalian organs. HFs are tiny and concealed within skin, whereas AUs are gigantic and grown externally for visual display. However, these two organs share some striking similarities. Both consist of permanent and cyclic/temporary components and undergo stem-cell-based organogenesis and cyclic regeneration. Stem cells of both organs reside in the permanent part and the growth centres are located in the temporary part of each respective organ. Organogenesis and regeneration of both organs depend on epithelial-mesenchymal interactions. Establishment of these interactions requires stem cells and reactive/niche cells (dermal papilla cells for HFs and epidermal cells for AUs) to be juxtaposed, which is achieved through destruction of the cyclic part to bring the reactive cells into close proximity to the respective stem cell niche. Developments of HFs and AUs are regulated by similar endocrine (particularly testosterone) and paracrine (particularly IGF1) factors. Interestingly, these two organs come to interplay during antlerogenesis. In conclusion, we believe that investigators from the fields of both HF and AU biology could greatly benefit from a comprehensive comparison between these two organs. PMID:24383056

Facile and Green Synthesis of Saturated Cyclic Amines

Directory of Open Access Journals (Sweden)

Arruje Hameed

2017-10-01

Full Text Available Single-nitrogen containing saturated cyclic amines are an important part of both natural and synthetic bioactive compounds. A number of methodologies have been developed for the synthesis of aziridines, azetidines, pyrrolidines, piperidines, azepanes and azocanes. This review highlights some facile and green synthetic routes for the synthesis of unsubstituted, multisubstituted and highly functionalized saturated cyclic amines including one-pot, microwave assisted, metal-free, solvent-free and in aqueous media.

Deformation localization and cyclic strength in polycrystalline molybdenum

Energy Technology Data Exchange (ETDEWEB)

Sidorov, O.T.; Rakshin, A.F.; Fenyuk, M.I.

1983-06-01

Conditions of deformation localization and its interrelation with cyclic strength in polycrystalline molybdenum were investigated. A fatigue failure of polycrystalline molybdenum after rolling and in an embrittled state reached by recrystallization annealing under cyclic bending at room temperature takes place under nonuniform distribution of microplastic strain resulting in a temperature rise in separate sections of more than 314 K. More intensive structural changes take place in molybdenum after rolling than in recrystallized state.

CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

DEFF Research Database (Denmark)

Jinquan, T; Quan, S; Jacobi, H H

2000-01-01

-induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 m......Ab blocked these functions of gammaIP-10 and Mig but not of chemokine stromal cell-derived factor 1 alpha. gamma IP-10-induced and Mig-induced up-regulation of integrins (CD49a and CD49b) was found to play a crucial role in adhesion of GM-CSF-stimulated CD34(+) progenitors. Moreover, gamma IP-10 and Mig...... stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment...

Cyclic elastic analysis of a PWR nozzle subjected to a repeated thermal shock

International Nuclear Information System (INIS)

Locci, J.M.; Prost, J.P.

1979-01-01

In the primary piping system of a PWR nuclear power plant, some nozzles are subjected to strong thermal shocks due to sudden thermal variations in the internal water flow. The thermal gradients are sufficiently high to induce general elastic plastic behaviour. The design of these nozzles using the simplified elastic plastic analysis given in the ASME III Code NB-3200 generally leads to a very high usage factor. The aim of this work is to show by giving an example that a complete cyclic elastic plastic analysis makes it possible to considerably reduce the usage factor. (orig.)

Induction of dopamine biosynthesis by l-DOPA in PC12 cells: implications of L-DOPA influx and cyclic AMP.

Science.gov (United States)

Jin, Chun Mei; Yang, Yoo Jung; Huang, Hai Shan; Lim, Sung Cil; Kai, Masaaki; Lee, Myung Koo

2008-09-04

The effects of 3,4-dihydroxyphenylalanine (l-DOPA) on dopamine biosynthesis and cytotoxicity were investigated in PC12 cells. l-DOPA treatment (20-200 microM) increased the levels of dopamine by 226%-504% after 3-6 h of treatment and enhanced the activities of tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase (AADC). l-DOPA (20-200 muM) treatment led to a 562%-937% increase in l-DOPA influx at 1 h, which inhibited the activity of TH, but not AADC, during the same period. The extracellular releases of dopamine were also increased by 231%-570% after treatment with 20 and 200 microM l-DOPA for 0.5-3 h. l-DOPA at a concentration of 100-200 microM, but not 20 microM, exerted apoptotic cytotoxicity towards PC12 cells for 24-48 h. l-DOPA (20-200 microM) increased the intracellular cyclic AMP levels by 318%-557% after 0.5-1 h in a concentration-dependent manner. However, the elevated cyclic AMP levels by l-DOPA could not protect against l-DOPA (100-200 microM)-induced cytotoxicity after 24-48 h. In addition, l-DOPA (20-200 microM)-induced increases in cyclic AMP and dopamine were significantly reduced by treatment with SCH23390 (dopamine D(1) receptor antagonist). The increased levels of dopamine by l-DOPA were also reduced by H89 (protein kinase A, PKA, inhibitor) and GF109203X (protein kinase C inhibitor); however, the reduction by GF109203X was not significant. l-DOPA at 20-200 microM stimulated the phosphorylation of PKA and cyclic AMP-response element binding protein and induced the biosynthesis of the TH protein. These results indicate that 20-200 microM l-DOPA induces dopamine biosynthesis by two pathways. One pathway involves l-DOPA directly entering the cells to convert dopamine through AADC activity (l-DOPA decarboxylation). The other pathway involves l-DOPA and/or released dopamine activating TH to enhance dopamine biosynthesis by the dopamine D(1) receptor-cyclic AMP-PKA signaling system (dopamine biosynthesis by TH).

Accelerated Cyclic Reduction: A Distributed-Memory Fast Solver for Structured Linear Systems

KAUST Repository

Chávez, Gustavo

2017-12-15

We present Accelerated Cyclic Reduction (ACR), a distributed-memory fast solver for rank-compressible block tridiagonal linear systems arising from the discretization of elliptic operators, developed here for three dimensions. Algorithmic synergies between Cyclic Reduction and hierarchical matrix arithmetic operations result in a solver that has O(kNlogN(logN+k2)) arithmetic complexity and O(k Nlog N) memory footprint, where N is the number of degrees of freedom and k is the rank of a block in the hierarchical approximation, and which exhibits substantial concurrency. We provide a baseline for performance and applicability by comparing with the multifrontal method with and without hierarchical semi-separable matrices, with algebraic multigrid and with the classic cyclic reduction method. Over a set of large-scale elliptic systems with features of nonsymmetry and indefiniteness, the robustness of the direct solvers extends beyond that of the multigrid solver, and relative to the multifrontal approach ACR has lower or comparable execution time and size of the factors, with substantially lower numerical ranks. ACR exhibits good strong and weak scaling in a distributed context and, as with any direct solver, is advantageous for problems that require the solution of multiple right-hand sides. Numerical experiments show that the rank k patterns are of O(1) for the Poisson equation and of O(n) for the indefinite Helmholtz equation. The solver is ideal in situations where low-accuracy solutions are sufficient, or otherwise as a preconditioner within an iterative method.

Accelerated Cyclic Reduction: A Distributed-Memory Fast Solver for Structured Linear Systems

KAUST Repository

Chá vez, Gustavo; Turkiyyah, George; Zampini, Stefano; Ltaief, Hatem; Keyes, David E.

2017-01-01

We present Accelerated Cyclic Reduction (ACR), a distributed-memory fast solver for rank-compressible block tridiagonal linear systems arising from the discretization of elliptic operators, developed here for three dimensions. Algorithmic synergies between Cyclic Reduction and hierarchical matrix arithmetic operations result in a solver that has O(kNlogN(logN+k2)) arithmetic complexity and O(k Nlog N) memory footprint, where N is the number of degrees of freedom and k is the rank of a block in the hierarchical approximation, and which exhibits substantial concurrency. We provide a baseline for performance and applicability by comparing with the multifrontal method with and without hierarchical semi-separable matrices, with algebraic multigrid and with the classic cyclic reduction method. Over a set of large-scale elliptic systems with features of nonsymmetry and indefiniteness, the robustness of the direct solvers extends beyond that of the multigrid solver, and relative to the multifrontal approach ACR has lower or comparable execution time and size of the factors, with substantially lower numerical ranks. ACR exhibits good strong and weak scaling in a distributed context and, as with any direct solver, is advantageous for problems that require the solution of multiple right-hand sides. Numerical experiments show that the rank k patterns are of O(1) for the Poisson equation and of O(n) for the indefinite Helmholtz equation. The solver is ideal in situations where low-accuracy solutions are sufficient, or otherwise as a preconditioner within an iterative method.

Waiting-time approximations in multi-queue systems with cyclic service

NARCIS (Netherlands)

Boxma, O.J.; Meister, B.W.

1987-01-01

This study is devoted to mean waiting-time approximations in a single-server multi-queue model with cyclic service and zero switching times of the server between consecutive queues. Two different service disciplines are considered: exhaustive service and (ordinary cyclic) nonexhaustive service. For

Ceramic breeder pebble bed packing stability under cyclic loads

Energy Technology Data Exchange (ETDEWEB)

Zhang, Chunbo, E-mail: chunbozhang@fusion.ucla.edu [Fusion Science and Technology Center, University of California, Los Angeles, CA 90095-1597 (United States); Ying, Alice; Abdou, Mohamed A. [Fusion Science and Technology Center, University of California, Los Angeles, CA 90095-1597 (United States); Park, Yi-Hyun [National Fusion Research Institute, Daejeon (Korea, Republic of)

2016-11-01

Highlights: • The feasibility of obtaining packing stability for pebble beds is studied. • The responses of pebble bed to cyclic loads have been presented and analyzed in details. • Pebble bed packing saturation and its applications are discussed. • A suggestion is made regarding the improvement of pebbles filling technique. - Abstract: Considering the optimization of blanket performance, it is desired that the bed morphology and packing state during reactor operation are stable and predictable. Both experimental and numerical work are performed to explore the stability of pebble beds, in particular under pulsed loading conditions. Uniaxial compaction tests have been performed for both KIT’s Li{sub 4}SiO{sub 4} and NFRI’s Li{sub 2}TiO{sub 3} pebble beds at elevated temperatures (up to 750 °C) under cyclic loads (up to 6 MPa). The obtained data shows the stress-strain loop initially moves towards the larger strain and nearly saturates after a certain number of cyclic loading cycles. The characterized FEM CAP material models for a Li{sub 4}SiO{sub 4} pebble bed with an edge-on configuration are used to simulate the thermomechanical behavior of pebble bed under ITER pulsed operations. Simulation results have shown the cyclic variation of temperature/stress/strain/gap and also the same saturation trend with experiments under cyclic loads. Therefore, it is feasible for pebble bed to maintain its packing stability during operation when disregarding pebbles’ breakage and irradiation.

INFLUENCE OF INTERMITTENT CYCLIC LOADING ON REINFORCED CONCRETE RESISTANCE MODEL

Directory of Open Access Journals (Sweden)

Vasyl Karpiuk

2017-01-01

Full Text Available This article describes the study of reinforced concrete span bending structures under conditions of high-level cyclic loading. Previous studies on the development of physical models of bending reinforced concrete element fatigue resistance, cyclic effect of lateral forces, and methods of calculation, are important and appropriate owing to certain features and the essential specificity of the mentioned loading type. These primarily include the nonlinearity of deformation, damage accumulation in the form of fatigue micro- and macro-cracks, and exhausting destruction of construction materials. In this paper, key expressions determining the endurance limits of concrete, longitudinal reinforcement, and anchoring longitudinal reinforcement, which contribute to endurance throughout the entire construction, are considered. Establishing a link between stresses in the elements and deformations in the element under conditions of cyclic loading action is of equal importance because of the presence of cyclic stress-induced creep deformation.

STRATEGIES FOR SUPERIOR PERFORMANCE IN RECESSIONS: PRO OR COUNTER-CYCLICAL?

Directory of Open Access Journals (Sweden)

Claudio Ramos Conti

2015-04-01

Full Text Available Recessions are recurring events in which most firms suffer severe impacts while others are less affected or may even prosper. Strategic management has made little progress in understanding such performance differences. In a scenario of decreased demand, intensified competition, and higher uncertainty, most firms try to survive by pro-cyclically cutting costs and investments. But firms could take advantage of undervalued resources in the market to counter-cyclically invest in new business opportunities to overtake competitors. We survey Brazilian firms in various industries about the 2008-2009 recession and analyze data using PLS-SEM. We find that while most firms pro-cyclically reduce costs and investments in recessions, a counter-cyclical strategy of investing in opportunities created by changes in the market enables superior performance. Most successful are firms with a propensity to recognize opportunities, an entrepreneurial orientation to invest, and the flexibility to efficiently implement investments.

Results on Cyclic Signal Processing Systems

National Research Council Canada - National Science Library

Vaidyanathan, P

1998-01-01

.... A number of related problems such as the paraunitary interpolation problem and the cyclic paraunitary factorizability problem can be understood in a unified way by using the realization matrix...

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

Science.gov (United States)

Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

Effects of multiaxial cyclic loading conditions on the evolution of porous defects

Directory of Open Access Journals (Sweden)

Mbiakop Armel

2014-06-01

Full Text Available Multiaxial loading conditions are one of the important parameters in estimating the lifetime of structure both in high and low cycle fatigue ([1 3]. In order to understand the coupling between the macroscopic multiaxial loading and the microscopic defects, we propose to investigate the evolution of an elasto-plastic porous material up to failure under low cycle fatigue conditions. The analysis is performed numerically, using finite elements, on a periodic 3D unit-cell under the assumption of finite strains and subjected to various stress triaxialities, translated as ratios between deviatoric, hydrostatic stress and Lode angles. The present discussion introduces several novel factors in the analysis: (i 3D geometry in cyclic loading (ii finite strains (iii free evolving void shape (iiii different hardening laws. That one of the important factors is the void shape and that its evolution during cyclic loading depends on its multiaxiality. Moreover, these factors will equally influence the apparent macroscopic hardening or softening of the material and the initiation of localized shear zones at the microscopic level. The Lode angle has a significant impact on the evolution of the aspect ratios and the ellipsoidicity of the pores, but has only a weak influence on the evolution of macroscopic variables such as the stress or the porosity. As a consequence, the results show that multiaxiality of the loading have an important on the evolution and growth of defects, pores in the present case problem, but are less important in the definition of the yield surface.

Isolation, nucleotide sequence and expression of a cDNA encoding feline granulocyte colony-stimulating factor.

Science.gov (United States)

Dunham, S P; Onions, D E

2001-06-21

A cDNA encoding feline granulocyte colony stimulating factor (fG-CSF) was cloned from alveolar macrophages using the reverse transcriptase-polymerase chain reaction. The cDNA is 949 bp in length and encodes a predicted mature protein of 174 amino acids. Recombinant fG-CSF was expressed as a glutathione S-transferase fusion and purified by affinity chromatography. Biological activity of the recombinant protein was demonstrated using the murine myeloblastic cell line GNFS-60, which showed an ED50 for fG-CSF of approximately 2 ng/ml. Copyright 2001 Academic Press.

Well screening for matrix stimulation treatments

International Nuclear Information System (INIS)

Saavedra, N; Solano, R; Gidley, J; Reyes, C.A; Rodriguez; Kondo, F; Hernandez, J

1998-01-01

Matrix acidizing is a stimulation technique only applicable to wells with surrounding damage. It is therefore very important to differentiate the real formation damage from the damage caused by flow Ni dynamic effects. The mechanical damage corresponds to flow restrictions caused by partial penetration, poor perforation as well as to reduce diameters of the production tubing. The dynamic effects are generated by inertia caused by high flow rates and high-pressure differentials. A common practice in our oil fields is to use a general formulation as acid treatment, most of the times without previous lab studies that guarantee the applicability of the treatment in the formation. Additionally, stimulation is randomly applied even treating undamaged wells with negative results and in the best of the cases, loss of the treatment. The selection of the well for matrix stimulation is an essential factor for the success of the treatment. Selection is done through the evaluation of the skin factor (S) and of the economic benefits of reducing the skin in comparison to the cost of the work. The most appropriate tool for skin evaluation is a good pressure test where the radial flow period can be identified. Nevertheless, we normally find-outdated tests most of the times taken with inaccurate tools. The interpretation problem is worsened by completions in which there is simultaneous production from several sand packages and it is difficult to individually differentiate damage factors. This works states a procedure for the selection of wells appropriate for stimulation; it also proposes a method to evaluate the skin factor when there are no accurate interpretations of the pressure tests. A new and increasingly applied methodology to treat wells with high water cuts, which are usually discarded due to the risk of stimulating water zones, is also mentioned

Introduction of a cyclic-fermentation method

Energy Technology Data Exchange (ETDEWEB)

Makarova, C P

1958-01-01

Equipment is described, consisting of 8 kettles, which permits a cyclic fermentation process and continuous ethanol production; 100% yields of ethanol are obtained, based on the starch content in grain.

Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

Science.gov (United States)

Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

1999-03-15

We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

Levels of cyclic-2,3-diphosphoglycerate in Methanobacterium thermoautotrophicum during phosphate limitation.

Science.gov (United States)

Seely, R J; Fahrney, D E

1984-10-01

Batch-grown Methanobacterium thermoautotrophicum cells grew nonexponentially in the absence of exogenous Pi until intracellular cyclic-2,3-diphosphoglycerate (cyclic DPG) had fallen below 2 mumol/g (dry weight), the limit of detection. Growth resumed immediately upon transfer to medium containing Pi Cyclic DPG levels were also below detection in Pi-limited chemostat cultures operating at a dilution rate of 0.173 h-1 (4-h doubling time), with reservoir Pi concentrations below 200 microM. At this dilution rate, the Pi concentration in the culture was 4 microM. An H2-limited steady state was achieved with 400 microM Pi in the inflowing medium (67 microM in the culture). The cyclic DPG content of these cells was 72 to 74 mumol/g, about one-third the amount in batch-grown cells. The specific growth rate accelerated immediately to 0.36 h-1 (1.9-h doubling time) under washout conditions at high dilution rate. The cellular content of cyclic DPG declined over a 2-h period, and then increased rapidly as the Pi level in the medium approached 200 microM. Expansion of the cyclic DPG pool coincided with a marked increase in Pi assimilation. These results indicated that M. thermoautotrophicum accumulated cyclic DPG only when Pi and H2 were readily available.

Levels of cyclic-2,3-diphosphoglycerate in Methanobacterium thermoautotrophicum during phosphate limitation.

Science.gov (United States)

Seely, R J; Fahrney, D E

1984-01-01

Batch-grown Methanobacterium thermoautotrophicum cells grew nonexponentially in the absence of exogenous Pi until intracellular cyclic-2,3-diphosphoglycerate (cyclic DPG) had fallen below 2 mumol/g (dry weight), the limit of detection. Growth resumed immediately upon transfer to medium containing Pi Cyclic DPG levels were also below detection in Pi-limited chemostat cultures operating at a dilution rate of 0.173 h-1 (4-h doubling time), with reservoir Pi concentrations below 200 microM. At this dilution rate, the Pi concentration in the culture was 4 microM. An H2-limited steady state was achieved with 400 microM Pi in the inflowing medium (67 microM in the culture). The cyclic DPG content of these cells was 72 to 74 mumol/g, about one-third the amount in batch-grown cells. The specific growth rate accelerated immediately to 0.36 h-1 (1.9-h doubling time) under washout conditions at high dilution rate. The cellular content of cyclic DPG declined over a 2-h period, and then increased rapidly as the Pi level in the medium approached 200 microM. Expansion of the cyclic DPG pool coincided with a marked increase in Pi assimilation. These results indicated that M. thermoautotrophicum accumulated cyclic DPG only when Pi and H2 were readily available. PMID:6480564

Factors stimulating content marketing

Directory of Open Access Journals (Sweden)

Naser Azad

2016-02-01

Full Text Available This paper presents an empirical investigation to determine factors influencing on content marketing in banking industry. The study designs a questionnaire consists of 40 questions in Likert scale and distributes it among 550 randomly selected regular customers of Bank Mellat in city of Tehran, Iran and 400 properly filled questionnaires are collected. Cronbach alphas for all components of the survey are well above desirable level. Using principle component analysis with Varimax rotation, the study has determined six factors influencing the most on content marketing including organization, details, having new ideas, quality, sensitivity and power while the last component contains only two subcomponents and is removed from the study.

A uniaxial cyclic elastoplastic constitutive law with a discrete memory variable

International Nuclear Information System (INIS)

Taheri, S.

1991-01-01

At present, the study on cyclic elastoplastic constitutive laws is focused on nonproportional loading, but for uniaxial loading, some problems still exist. For example, the possibility for a law to describe simultaneously the ratcheting in nonsymmetrical load-controlled test, elastic and plastic shakedown in symmetrical and nonsymmetrical ones. Here a law is presented, which in addition to previous phenomena, describes the cyclic hardening in a pushpull test, the cyclic softening after overloading and also the dependence of cyclic strain-stress curves on the history of loading. These are the usual properties of 316 stainless steel at room temperature. This law uses an internal discrete memory variable: the plastic strain at the last unloading. On the other hand, the choice of all macroscopic variables is justified by a microscopic analysis. This law has been also extended to a three-dimensional case. Regarding the microstructure under cyclic loading, plastic shakedown and ratcheting are discussed. The definition of macroscopic variables taking account of microstructure and uniaxial constitutive law are described. (K.I.)

Earl Sutherland (1915-1974) [corrected] and the discovery of cyclic AMP.

Science.gov (United States)

Blumenthal, Stanley A

2012-01-01

In 1945, Earl Sutherland (1915-1974) [corrected] and associates began studies of the mechanism of hormone-induced glycogen breakdown in the liver. In 1956, their efforts culminated in the identification of cyclic AMP, an ancient molecule generated in many cell types in response to hormonal and other extracellular signals. Cyclic AMP, the original "second messenger," transmits such signals through pathways that regulate a diversity of cellular functions and capabilities: metabolic processes such as lipolysis and glycogenolysis; hormone secretion; the permeability of ion channels; gene expression; cell proliferation and survival. Indeed, it can be argued that the discovery of cyclic AMP initiated the study of intracellular signaling pathways, a major focus of contemporary biomedical inquiry. This review presents relevant details of Sutherland's career; summarizes key contributions of his mentors, Carl and Gerti Cori, to the knowledge of glycogen metabolism (contributions that were the foundation for his own research); describes the experiments that led to his identification, isolation, and characterization of cyclic AMP; assesses the significance of his work; and considers some aspects of the impact of cyclic nucleotide research on clinical medicine.

Synthesis of Cyclic Antifreeze Glycopeptide and Glycopeptoids and Their Ice Recrystallization Inhibition Activity

International Nuclear Information System (INIS)

Ahn, Mija; Murugan, Ravichandran N.; Bang, Jeong Kyu; Kim, Hak Jun; Shin, Song Yub; Kim, Eunjung; Lee, Jun Hyuck

2012-01-01

Until now, few groups reported the antifreeze activity of cyclic glycopeptides; however, the tedious synthetic procedure is not amenable to study the intensive structure activity relationship. A series of N-linked cyclic glycopeptoids and glycopeptide have been prepared to evaluate antifreeze activity as a function of peptide backbone cyclization and methyl stereochemical effect on the rigid Thr position. This study has combined the cyclization protocol with solid phase peptide synthesis and obtained significant quantities of homogeneous cyclic glycopeptide and glycopeptoids. Analysis of antifreeze activity revealed that our cyclic peptide demonstrated RI activity while cyclic glycopeptoids showed no RI activity. These results suggest that the subtle changes in conformation and Thr orientation dramatically influence RI activity of N-linked glycopeptoids

Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction.

Directory of Open Access Journals (Sweden)

Stéphanie eOlière

2013-09-01

Full Text Available Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamine. Interestingly, recent accumulating evidence points toward the involvement of the endocannabinoid system (ECBS in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep-insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. The aims of this article are to: 1 review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and 2 evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoid in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants.

Cyclic complex loading of 316 stainless steel: Experiments and calculations

International Nuclear Information System (INIS)

Jacquelin, B.; Hourlier, F.; Dang Van, K.; Stolz, C.

1981-01-01

To test the ability of cyclic constitutive law established by mean of uniaxial test a benchmark is proposed. The calculated results using the model of Chaboche-Cordier-Dang Van are compared with experimental data obtained on cylindrical specimens undergoing simultaneously constant torque and cyclic tension. (orig.)

The effect of ultraviolet light on the cyclic nucleotide system of human fibroblasts

International Nuclear Information System (INIS)

Fertel, R.H.; Tejwani, G.A.; Albrightson, C.R.; Hart, R.W.

1981-01-01

The concentrations of cyclic AMP and cyclic GMP in in human skin fibroblasts in culture were determined after exposing the cells to varying fluences of UV (254 nm) light. The cyclic nucleotide concentrations of cells irradiated in the log phase of growth were unchanged relative to controls. In contrast, there was a rise in the concentration of cyclic AMP in cells irradiated after they reached confluency. The increase in concentration was observed as early as 30 min after irradiation, reached a maximum of about 200% of control at 4 to 6 h after exposure, and returned to control values by 24 h after irradiation. The effect was proportional to a UV fluence from 5 to 20 J/m 2 , and was blocked by the addition of the UV absorbing agent para-aminobenzoic acid. In contrast, the results indicated that UV light had no effect on the concentration of cyclic GMP in human fibroblast cell cultures. Because of the importance of cyclic nucleotides in the regulation of cellular function, it is reasonable to hypothesize that changes in cyclic AMP induced by UV light may effect the extranuclear functions of irradiated cells. (author)

The interplay between seasonality and density: consequences for female breeding decisions in a small cyclic herbivore.

Science.gov (United States)

Pinot, Adrien; Gauffre, Bertrand; Bretagnolle, Vincent

2014-05-28

Cyclic rodent population dynamics are subjected to both intrinsic regulatory processes such as density-dependence and extrinsic environmental forcing. Among extrinsic factors, seasonal environmental variation is understood to facilitate cycles. In rodents, these processes have been studied mostly independently and their relative importance for population dynamics is poorly known. We performed a detailed analysis of common vole (Microtus arvalis) reproduction in a cyclic population using a spatially extensive data set over 17 years in central-western France. Environmental seasonality was the main source of explained variation in common vole reproduction. Additionally, inter-annual variation in the environment explained a smaller part of the variance in reproduction in spring and summer than in winter, whereas the effect of density was only found in autumn and winter. In particular, we detected a strong impact of plant productivity on fecundity during the breeding season, with low vegetation productivity being able to bring vole reproduction nearly to a halt. In contrast, vole reproduction during autumn and winter was mainly shaped by intrinsic factors, with only the longer and heavier females being able to reproduce. The effect of population density on reproduction was negative, mediated by direct negative effects on the proportion of breeders in autumn and winter during outbreak years and by a delayed negative effect on litter size the following year. During the main breeding season, variability of female vole reproduction is predominantly shaped by food resources, suggesting that only highly productive environment may induce vole outbreaks. During fall and winter, variability of female vole reproduction is mainly controlled by intrinsic factors, with high population density suppressing reproduction. This suggests, in this cyclic population, that negative direct density dependence on reproduction could explain winter declines after outbreaks.

The role of granulocyte macrophage-colony stimulating factor in gastrointestinal immunity to salmonellosis.

Science.gov (United States)

Coon, C; Beagley, K W; Bao, S

2009-08-01

Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host's immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF(-/-) mice. Furthermore, GM-CSF(-/-) mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80+ effector cells. Moreover in the absence of GM-CSF, a decrease in pro-inflammatory cytokine expression of tumor necrosis factor-alpha, interleukin-12 (IL-12) and IL-18 was found, which may alter the host's immune response to infection. GM-CSF appears to play an important role in the pathogenesis of Salmonellosis, and may contribute significantly to the development of protective gastrointestinal mucosal immune responses against oral pathogens.

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

Directory of Open Access Journals (Sweden)

Stylianos Michalakis

2018-03-01

Full Text Available The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP or cyclic adenosine monophosphate (cAMP. Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN channels and voltage-gated potassium channels (KCN. In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application.

Cyclic Nucleotide Monophosphates and Their Cyclases in Plant Signaling

KAUST Repository

Gehring, Christoph A; Turek, Ilona S.

2017-01-01

The cyclic nucleotide monophosphates (cNMPs), and notably 3′,5′-cyclic guanosine monophosphate (cGMP) and 3′,5′-cyclic adenosine monophosphate (cAMP) are now accepted as key signaling molecules in many processes in plants including growth and differentiation, photosynthesis, and biotic and abiotic defense. At the single molecule level, we are now beginning to understand how cNMPs modify specific target molecules such as cyclic nucleotide-gated channels, while at the systems level, a recent study of the Arabidopsis cNMP interactome has identified novel target molecules with specific cNMP-binding domains. A major advance came with the discovery and characterization of a steadily increasing number of guanylate cyclases (GCs) and adenylate cyclases (ACs). Several of the GCs are receptor kinases and include the brassinosteroid receptor, the phytosulfokine receptor, the Pep receptor, the plant natriuretic peptide receptor as well as a nitric oxide sensor. We foresee that in the near future many more molecular mechanisms and biological roles of GCs and ACs and their catalytic products will be discovered and further establish cNMPs as a key component of plant responses to the environment.

Cyclic Nucleotide Monophosphates and Their Cyclases in Plant Signaling

KAUST Repository

Gehring, Christoph A.

2017-10-04

The cyclic nucleotide monophosphates (cNMPs), and notably 3′,5′-cyclic guanosine monophosphate (cGMP) and 3′,5′-cyclic adenosine monophosphate (cAMP) are now accepted as key signaling molecules in many processes in plants including growth and differentiation, photosynthesis, and biotic and abiotic defense. At the single molecule level, we are now beginning to understand how cNMPs modify specific target molecules such as cyclic nucleotide-gated channels, while at the systems level, a recent study of the Arabidopsis cNMP interactome has identified novel target molecules with specific cNMP-binding domains. A major advance came with the discovery and characterization of a steadily increasing number of guanylate cyclases (GCs) and adenylate cyclases (ACs). Several of the GCs are receptor kinases and include the brassinosteroid receptor, the phytosulfokine receptor, the Pep receptor, the plant natriuretic peptide receptor as well as a nitric oxide sensor. We foresee that in the near future many more molecular mechanisms and biological roles of GCs and ACs and their catalytic products will be discovered and further establish cNMPs as a key component of plant responses to the environment.

Evolution of the cyclic plastic response of Sanicro 25 steel cycled at ambient and elevated temperatures

Czech Academy of Sciences Publication Activity Database

Polák, Jaroslav; Petráš, Roman; Heczko, Milan; Kruml, Tomáš; Chai, G.

2016-01-01

Roč. 83, FEB (2016), s. 75-83 ISSN 0142-1123 R&D Projects: GA ČR(CZ) GA13-23652S Institutional support: RVO:68081723 Keywords : Cyclic plastic ity * Hysteresis loop analysis * Heat resistant steel * Dislocation structure * Effect of temperature Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.899, year: 2016

The participation of elevated levels of cyclic GMP in the recovery from radiation-induced mitotic delay

International Nuclear Information System (INIS)

Daniel, J.W.; Oleinick, N.L.

1984-01-01

The levels of cyclic AMP and cyclic GMP have been measured in Physarum plasmodia before and after treatment with gamma-radiation, 2 mM caffeine, or combinations of the two agents compared to the length of the radiation-induced mitotic delay. Caffeine alone produces a rapid transient elevation of cyclic AMP and a slower delayed elevation of cyclic GMP. Irradiation elicits an immediate transient increase in cyclic AMP and a later cyclic GMP increase which accompanies or precedes the delayed mitosis. A composite pattern is produced by combinations of radiation and caffeine, a distinctive feature of which is an elevated level of cyclic GMP near the time of the radiation-delayed and caffeine-promoted mitosis. With pretreatment by caffeine, the least radiation-induced mitotic delay occurs when plasmodia are irradiated during the caffeine-elicited increase in cyclic GMP. The plasmodium becomes refractory to the reduction of mitotic delay by caffeine at approximately the time it becomes refractory to the further elevation of cyclic GMP by caffeine. The data support a role for cyclic AMP in the onset of and for cyclic GMP in the recovery from mitotic delay induced by ionizing radiation. (author)

High cyclic fatigue of PWR primary piping generated by the pressure pulsations in coolant

International Nuclear Information System (INIS)

Zd'arek, J.; Pecinka, L.; Zeman, V.

1999-01-01

The protection of nuclear piping Class 1, 2 and 3 against fatigue failure is according to standard western practise and is based on - determining the cumulative usage factor (CUF) using equation (11) of ASME Code, Section III, Article NB 3653 for Class 1 piping; - Markl experiments and equation (10) of ASME Code, Section III, Article NC/ND 3653 for Class 2/3 piping. These evaluations cover only low cyclic loading and the possible influence of high cyclic loading as for example vibratory stresses generated by the main circulating pumps are not taken into account. This problem is fully covered in the Czech and Russian codes. The goal of this paper is 1. to clarify the basic principles; 2. to discuss in detail the methodology for the calculation of high frequency vibratory stresses; and 3. to demonstrate with a numerical example, the degree of influence of the CUF. (orig.)

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

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Magda Paula Pereira do Nascimento

2011-09-01

Full Text Available Multinucleated giant cells (MGC are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF in association with other cytokines such as interferon-gamma (IFN-γ, tumour necrosis factor-alpha, interleukin (IL-10 or transforming growth factor beta (TGF-β1 on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg. The generation of MGC was determined by fusion index (FI and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18. The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18.

Numerical modeling of centrifuge cyclic lateral pile load experiments

Science.gov (United States)

Gerolymos, Nikos; Escoffier, Sandra; Gazetas, George; Garnier, Jacques

2009-03-01

To gain insight into the inelastic behavior of piles, the response of a vertical pile embedded in dry sand and subjected to cyclic lateral loading was studied experimentally in centrifuge tests conducted in Laboratoire Central des Ponts et Chaussées. Three types of cyclic loading were applied, two asymmetric and one symmetric with respect to the unloaded pile. An approximately square-root variation of soil stiffness with depth was obtained from indirect in-flight density measurements, laboratory tests on reconstituted samples, and well-established empirical correlations. The tests were simulated using a cyclic nonlinear Winkler spring model, which describes the full range of inelastic phenomena, including separation and re-attachment of the pile from and to the soil. The model consists of three mathematical expressions capable of reproducing a wide variety of monotonic and cyclic experimental p-y curves. The physical meaning of key model parameters is graphically explained and related to soil behavior. Comparisons with the centrifuge test results demonstrate the general validity of the model and its ability to capture several features of pile-soil interaction, including: soil plastification at an early stage of loading, “pinching” behavior due to the formation of a relaxation zone around the upper part of the pile, and stiffness and strength changes due to cyclic loading. A comparison of the p-y curves derived from the test results and the proposed model, as well as those from the classical curves of Reese et al. (1974) for sand, is also presented.

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial.

Science.gov (United States)

Aleyasin, Ashraf; Abediasl, Zhila; Nazari, Atefeh; Sheikh, Mahdi

2016-06-01

Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P=0.007), chemical pregnancy (44.6% vs 19.6%, P=0.005), and clinical pregnancy (37.5% vs 14.3%, P=0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR=2.63, 95% CI=1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI=1.11-7.38) and clinical pregnancy (OR=2.94, 95% CI=1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure. © 2016 Society for Reproduction and Fertility.

Soluble lymphocytic mediators

Science.gov (United States)

Pick, E.

1974-01-01

The effect of a number of drugs on the production of macrophage migration inhibitory factor (MIF) by antigen-stimulated sensitized guinea-pig lymph node cells was studied. The drugs were present during the entire culture period and eliminated from supernatants by dialysis. It was found that MIF secretion is inhibited by exogenous dibutyryl cyclic AMP and by theophylline and chlorphenesin, two agents raising the endogenous level of cyclic AMP. On the other hand, isoproterenol, which stimulates cyclic AMP generation in several tissues, did not block MIF production. The formation of the mediator was also suppressed by the microfilament-affecting drug, cytochalasin B. The microtubular disruptive agents, colchicine and vinblastine sulphate, did not influence MIF production. It is concluded that: (a) endogenous cyclic AMP may act as a regulator of MIF production; (b) the activity of contractile microfilaments is probably required for MIF formation; and (c) microtubules are not involved in the secretory process. PMID:4369184

Toxicity and uptake of cyclic nitramine explosives in ryegrass Lolium perenne

International Nuclear Information System (INIS)

Rocheleau, Sylvie; Lachance, Bernard; Kuperman, Roman G.; Hawari, Jalal; Thiboutot, Sonia; Ampleman, Guy; Sunahara, Geoffrey I.

2008-01-01

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) are cyclic nitramines used as explosives. Their ecotoxicities have been characterized incompletely and little is known about their accumulation potential in soil organisms. We assessed the toxicity and uptake of these explosives in perennial ryegrass Lolium perenne L. exposed in a Sassafras sandy loam (SSL) or in a sandy soil (DRDC, CL-20 only) containing contrasting clay contents (11% and 0.3%, respectively). A 21-d exposure to RDX, HMX or CL-20 in either soil had no adverse effects on ryegrass growth. RDX and HMX were translocated to ryegrass shoots, with bioconcentration factors (BCF) of up to 15 and 11, respectively. In contrast, CL-20 was taken up by the roots (BCF up to 19) with no translocation to the shoots. These studies showed that RDX, HMX, and CL-20 can accumulate in plants and may potentially pose a risk of biomagnification across the food chain. - Cyclic nitramine explosives accumulate in perennial ryegrass and exhibit distinct uptake patterns

Toxicity and uptake of cyclic nitramine explosives in ryegrass Lolium perenne

Energy Technology Data Exchange (ETDEWEB)

Rocheleau, Sylvie; Lachance, Bernard [Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2 (Canada); Kuperman, Roman G. [Edgewood Chemical Biological Center, 5183 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5424 (United States); Hawari, Jalal [Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2 (Canada); Thiboutot, Sonia; Ampleman, Guy [Defense Research and Development Canada, 2459 Pie IX Boulevard, Val Belair, Quebec G3J 1X5 (Canada); Sunahara, Geoffrey I. [Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2 (Canada)], E-mail: geoffrey.sunahara@cnrc-nrc.gc.ca

2008-11-15

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), and 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) are cyclic nitramines used as explosives. Their ecotoxicities have been characterized incompletely and little is known about their accumulation potential in soil organisms. We assessed the toxicity and uptake of these explosives in perennial ryegrass Lolium perenne L. exposed in a Sassafras sandy loam (SSL) or in a sandy soil (DRDC, CL-20 only) containing contrasting clay contents (11% and 0.3%, respectively). A 21-d exposure to RDX, HMX or CL-20 in either soil had no adverse effects on ryegrass growth. RDX and HMX were translocated to ryegrass shoots, with bioconcentration factors (BCF) of up to 15 and 11, respectively. In contrast, CL-20 was taken up by the roots (BCF up to 19) with no translocation to the shoots. These studies showed that RDX, HMX, and CL-20 can accumulate in plants and may potentially pose a risk of biomagnification across the food chain. - Cyclic nitramine explosives accumulate in perennial ryegrass and exhibit distinct uptake patterns.

Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.

Science.gov (United States)