Molecular Stress-inducing Compounds Increase Osteoclast Formation in a Heat Shock Factor 1 Protein-dependent Manner*

Science.gov (United States)

Chai, Ryan C.; Kouspou, Michelle M.; Lang, Benjamin J.; Nguyen, Chau H.; van der Kraan, A. Gabrielle J.; Vieusseux, Jessica L.; Lim, Reece C.; Gillespie, Matthew T.; Benjamin, Ivor J.; Quinn, Julian M. W.; Price, John T.

2014-01-01

Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss. PMID:24692538

Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner.

Science.gov (United States)

Chai, Ryan C; Kouspou, Michelle M; Lang, Benjamin J; Nguyen, Chau H; van der Kraan, A Gabrielle J; Vieusseux, Jessica L; Lim, Reece C; Gillespie, Matthew T; Benjamin, Ivor J; Quinn, Julian M W; Price, John T

2014-05-09

Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss.

A Novel mouse model of enhanced proteostasis: Full-length human heat shock factor 1 transgenic mice

International Nuclear Information System (INIS)

Pierce, Anson; Wei, Rochelle; Halade, Dipti; Yoo, Si-Eun; Ran, Qitao; Richardson, Arlan

2010-01-01

Research highlights: → Development of mouse overexpressing native human HSF1 in all tissues including CNS. → HSF1 overexpression enhances heat shock response at whole-animal and cellular level. → HSF1 overexpression protects from polyglutamine toxicity and favors aggresomes. → HSF1 overexpression enhances proteostasis at the whole-animal and cellular level. -- Abstract: The heat shock response (HSR) is controlled by the master transcriptional regulator heat shock factor 1 (HSF1). HSF1 maintains proteostasis and resistance to stress through production of heat shock proteins (HSPs). No transgenic model exists that overexpresses HSF1 in tissues of the central nervous system (CNS). We generated a transgenic mouse overexpressing full-length non-mutant HSF1 and observed a 2-4-fold increase in HSF1 mRNA and protein expression in all tissues studied of HSF1 transgenic (HSF1 +/0 ) mice compared to wild type (WT) littermates, including several regions of the CNS. Basal expression of HSP70 and 90 showed only mild tissue-specific changes; however, in response to forced exercise, the skeletal muscle HSR was more elevated in HSF1 +/0 mice compared to WT littermates and in fibroblasts following heat shock, as indicated by levels of inducible HSP70 mRNA and protein. HSF1 +/0 cells elicited a significantly more robust HSR in response to expression of the 82 repeat polyglutamine-YFP fusion construct (Q82YFP) and maintained proteasome-dependent processing of Q82YFP compared to WT fibroblasts. Overexpression of HSF1 was associated with fewer, but larger Q82YFP aggregates resembling aggresomes in HSF1 +/0 cells, and increased viability. Therefore, our data demonstrate that tissues and cells from mice overexpressing full-length non-mutant HSF1 exhibit enhanced proteostasis.

Resveratrol Reactivates Latent HIV through Increasing Histone Acetylation and Activating Heat Shock Factor 1.

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Zeng, Xiaoyun; Pan, Xiaoyan; Xu, Xinfeng; Lin, Jian; Que, Fuchang; Tian, Yuanxin; Li, Lin; Liu, Shuwen

2017-06-07

The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC). However, latent HIV was reactivated by resveratrol mediated through increasing histone acetylation and activation of heat shock factor 1 (HSF1). Additionally, synergistic activation of the latent HIV reservoirs was observed under cotreatment with resveratrol and conventional LRAs. Collectively, this research reveals that resveratrol is a natural LRA and shows promise for HIV therapy.

Generation of Two Successive Shock Waves Focusedto a Common Focal Point

Czech Academy of Sciences Publication Activity Database

Šunka, Pavel; Stelmashuk, Vitaliy; Babický, Václav; Člupek, Martin; Beneš, J.; Poučková, P.; Kašpar, J.; Bodnár, M.

2006-01-01

Roč. 34, č. 4 (2006), s. 1382-1385 ISSN 0093-3813. [International Power Modulator Conference. Washington D.C., 14.5.2006-18.5.2006] R&D Projects: GA ČR(CZ) GA202/05/0685 Institutional research plan: CEZ:AV0Z20430508 Keywords : Cavitation collpse * double shocks * focused shock waves * liver injury * secondary shocks Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.144, year: 2006

Heat shock instructs hESCs to exit from the self-renewal program through negative regulation of OCT4 by SAPK/JNK and HSF1 pathway.

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Byun, Kyunghee; Kim, Taek-Kyun; Oh, Jeehyun; Bayarsaikhan, Enkhjargal; Kim, Daesik; Lee, Min Young; Pack, Chan-Gi; Hwang, Daehee; Lee, Bonghee

2013-11-01

Environmental factors affect self-renewal of stem cells by modulating the components of self-renewal networks. Heat shock, an environmental factor, induces heat shock factors (HSFs), which up-regulate stress response-related genes. However, the link of heat shock to self-renewal of stem cells has not been elucidated yet. Here, we present the direct link of heat shock to a core stem cell regulator, OCT4, in the self-renewal network through SAPK/JNK and HSF1 pathway. We first showed that heat shock initiated differentiation of human embryonic stem cells (hESCs). Gene expression analysis revealed that heat shock increased the expression of many genes involved in cellular processes related to differentiation of stem cells. We then examined the effects of HSFs induced by heat shock on core self-renewal factors. Among HSFs, heat shock induced mainly HSF1 in hESCs. The HSF1 repressed the expression of OCT4, leading to the differentiation of hESCs and the above differentiation-related gene expression change. We further examined the effects of the upstream MAP (mitogen-activated protein) kinases of HSF1 on the repression of OCT4 expression by HSF1. Among the MAP kinases, SAPK/JNK controlled predominantly the repression of the OCT4 expression by HSF1. The direct link of heat shock to the core self-renewal regulator through SAPK/JNK and HSF1 provides a fundamental basis for understanding the effect of heat and other stresses involving activation of HSF1 on the self-renewal program and further controlling differentiation of hESCs in a broad spectrum of stem cell applications using these stresses. © 2013.

Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1.

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Kusumoto, Hiroki; Hirohashi, Yoshihiko; Nishizawa, Satoshi; Yamashita, Masamichi; Yasuda, Kazuyo; Murai, Aiko; Takaya, Akari; Mori, Takashi; Kubo, Terufumi; Nakatsugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Kondo, Toru; Sato, Noriyuki; Hara, Isao; Torigoe, Toshihiko

2018-03-01

In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT-PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem-like cells. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Monitoring the Induction of Heat Shock Factor 1/Heat Shock Protein 70 Expression following 17-Allylamino-Demethoxygeldanamycin Treatment by Positron Emission Tomography and Optical Reporter Gene Imaging

Directory of Open Access Journals (Sweden)

Mikhail Doubrovin

2012-01-01

Full Text Available The cell response to proteotoxic cell stresses is mediated primarily through activation of heat shock factor 1 (HSF1. This transcription factor plays a major role in the regulation of the heat shock proteins (HSPs, including HSP70. We demonstrate that an [124I]iodide-pQHNIG70 positron emission tomography (PET reporter system that includes an inducible HSP70 promoter can be used to image and monitor the activation of the HSF1/HSP70 transcription factor in response to drug treatment (17-allylamino-demethoxygeldanamycin [17-AAG]. We developed a dual imaging reporter (pQHNIG70 for noninvasive imaging of the heat shock response in cell culture and living animals previously and now study HSF1/HSP70 reporter activation in both cell culture and tumor-bearing animals following exposure to 17-AAG. 17-AAG (10–1,000 nM induced reporter expression; a 23-fold increase was observed by 60 hours. Good correspondence between reporter expression and HSP70 protein levels were observed. MicroPET imaging based on [124I]iodide accumulation in pQHNIG70-transduced RG2 xenografts showed a significant 6.2-fold reporter response to 17-AAG, with a corresponding increase in tumor HSP70 and in tumor human sodium iodide symporter and green fluorescent protein reporter proteins. The HSF1 reporter system can be used to screen anticancer drugs for induction of cytotoxic stress and HSF1 activation both in vitro and in vivo.

Increased expression of heat shock protein 70 and heat shock factor 1 in chronic dermal ulcer tissues treated with laser-aided therapy.

Science.gov (United States)

Zhou, Jian-da; Luo, Cheng-qun; Xie, Hui-qing; Nie, Xin-min; Zhao, Yan-zhong; Wang, Shao-hua; Xu, Yi; Pokharel, Pashupati Babu; Xu, Dan

2008-07-20

Chronic dermal ulcers are also referred to as refractory ulcers. This study was conducted to elucidate the therapeutic effect of laser on chronic dermal ulcers and the induced expression of heat shock factor 1 (HSF1) and heat shock protein 70 (HSP70) in wound tissues. Sixty patients with 84 chronic dermal ulcers were randomly divided into traditional therapy and laser therapy groups. Laser treatment was performed in addition to traditional therapy in the laser therapy group. The treatment efficacy was evaluated after three weeks. Five tissue sections of healing wounds were randomly collected along with five normal skin sections as controls. HSP70-positive cells from HSP70 immunohistochemical staining were counted and the gray scale of positive cells was measured for statistical analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the mRNA and protein expressions of HSF1 and HSP70. The cure rate of the wounds and the total efficacy in the laser therapy group were significantly higher than those in the traditional therapy group (P ulcers plays a facilitating role in healing due to the mechanism of laser-activated endogenous heat shock protection in cells in wound surfaces.

Heat shock transcription factors regulate heat induced cell death in a ...

Indian Academy of Sciences (India)

2007-03-29

Mar 29, 2007 ... Heat shock transcription factors regulate heat induced cell death in a rat ... the synthesis of heat shock proteins (Hsps) which is strictly regulated by ... The lack of Hsp synthesis in these cells was due to a failure in HSF1 DNA ...

Trehalose: a biophysics approach to modulate the inflammatory response during endotoxic shock.

Science.gov (United States)

Minutoli, Letteria; Altavilla, Domenica; Bitto, Alessandra; Polito, Francesca; Bellocco, Ersilia; Laganà, Giuseppina; Fiumara, Tiziana; Magazù, Salvatore; Migliardo, Federica; Venuti, Francesco Saverio; Squadrito, Francesco

2008-07-28

We evaluated the effects of trehalose against endotoxic shock, a condition in which the loss of bio-membrane integrity plays a pivotal role. In addition we performed a biophysics experiment by quasi elastic neutron scattering (QENS) study, to investigate whether the membrane stability effect of trehalose might be correlated with its high capability to switch-off the water diffusive dynamics and, hence, the kinetic mechanisms of interaction. Endotoxic shock was induced in male rats by a single injection of Salmonella enteritidis lipopolysaccharide (LPS; 20 mg/kg/i.p.). Thirty minutes before and 2 h after LPS injection, the animals were randomized to receive vehicle (1 ml/kg/i.p. 0.9%NaCl), sucrose (1 g/kg/i.p.) or trehalose (1 g/kg/i.p.). Mean arterial blood pressure, nuclear factor-kappaB (NF-kappaB) binding activity, Ikappa-Balpha and toll-like receptor-4 (TLR-4) activation were evaluated in both liver and lung. Plasmatic tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and malondialdehyde (MDA) were also investigated. We studied liver injury by means of blood alanine aminotransferase activity (ALT); inducible nitric oxide synthase (iNOS) expression, myeloperoxidase (MPO) activity and tissue edema evaluation. Lung injury was investigated by means of tissue monocyte chemoattractant protein-1 (MCP-1) levels, MPO activity, iNOS expression and edema formation. Trehalose reduced hypotension, NF-kappaB binding activity, IkappaBalpha protein loss and TLR-4 activation. In addition trehalose reduced TNF-alpha, IL-1, IL-6 and MDA levels. Trehalose also blunted liver and lung injury. QENS measurements showed also that trehalose possesses a high "switching off" capability. Sucrose did not modify endotoxic shock-induced sequelae. Trehalose blocked the inflammatory cascade triggered by endotoxin shock, stabilizing the bio-membranes and switching off the water diffusive dynamics.

Discovering a Reliable Heat-Shock Factor-1 Inhibitor to Treat Human Cancers: Potential Opportunity for Phytochemists

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Murugesan Velayutham

2018-04-01

Full Text Available Heat-shock factor-1 (HSF-1 is an important transcription factor that regulates pathogenesis of many human diseases through its extensive transcriptional regulation. Especially, it shows pleiotropic effects in human cancer, and hence it has recently received increased attention of cancer researchers. After myriad investigations on HSF-1, the field has advanced to the phase where there is consensus that finding a potent and selective pharmacological inhibitor for this transcription factor will be a major break-through in the treatment of various human cancers. Presently, all reported inhibitors have their limitations, made evident at different stages of clinical trials. This brief account summarizes the advances with tested natural products as HSF-1 inhibitors and highlights the necessity of phytochemistry in this endeavor of discovering a potent pharmacological HSF-1 inhibitor.

Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

Science.gov (United States)

Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa

2013-01-01

Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (pmuscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.

Fresh Frozen Plasma Modulates Brain Gene Expression in a Swine Model of Traumatic Brain Injury and Shock

DEFF Research Database (Denmark)

Sillesen, Martin; Bambakidis, Ted; Dekker, Simone E

2017-01-01

BACKGROUND: Resuscitation with fresh frozen plasma (FFP) decreases brain lesion size and swelling in a swine model of traumatic brain injury and hemorrhagic shock. We hypothesized that brain gene expression profiles after traumatic brain injury and hemorrhagic shock would be modulated by FFP resu...

Anticipation of electric shocks modulates low beta power and event-related fields during memory encoding.

Science.gov (United States)

Bauch, Eva M; Bunzeck, Nico

2015-09-01

In humans, the temporal and oscillatory dynamics of pain anticipation and its effects on long-term memory are largely unknown. Here, we investigated this open question by using a previously established behavioral paradigm in combination with magnetoencephalography (MEG). Healthy human subjects encoded a series of scene images, which was combined with cues predicting an aversive electric shock with different probabilities (0.2, 0.5 or 0.8). After encoding, memory for the studied images was tested using a remember/know recognition task. Behaviorally, pain anticipation did not modulate recollection-based recognition memory per se, but interacted with the perceived unpleasantness of the electric shock [visual analogue scale rating from 1 (not unpleasant) to 10 (highly unpleasant)]. More precisely, the relationship between pain anticipation and recollection followed an inverted u-shaped function the more unpleasant the shocks were rated by a subject. At the physiological level, this quadratic effect was mimicked in the event-related magnetic fields associated with successful memory formation ('DM-effect') ∼450ms after image onset at left frontal sensors. Importantly, across all subjects, shock anticipation modulated oscillatory power in the low beta frequency range (13-20Hz) in a linear fashion at left temporal sensors. Taken together, our findings indicate that beta oscillations provide a generic mechanism underlying pain anticipation; the effect on subsequent long-term memory, on the other hand, is much more variable and depends on the level of individual pain perception. As such, our findings give new and important insights into how aversive motivational states can drive memory formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Possible Contribution of Zerumbone-Induced Proteo-Stress to Its Anti-Inflammatory Functions via the Activation of Heat Shock Factor 1.

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Yoko Igarashi

Full Text Available Zerumbone is a sesquiterpene present in Zinger zerumbet. Many studies have demonstrated its marked anti-inflammatory and anti-carcinogenesis activities. Recently, we showed that zerumbone binds to numerous proteins with scant selectivity and induces the expression of heat shock proteins (HSPs in hepatocytes. To dampen proteo-toxic stress, organisms have a stress-responsive molecular machinery, known as heat shock response. Heat shock factor 1 (HSF1 plays a key role in this protein quality control system by promoting activation of HSPs. In this study, we investigated whether zerumbone-induced HSF1 activation contributes to its anti-inflammatory functions in stimulated macrophages. Our findings showed that zerumbone increased cellular protein aggregates and promoted nuclear translocation of HSF1 for HSP expression. Interestingly, HSF1 down-regulation attenuated the suppressive effects of zerumbone on mRNA and protein expressions of pro-inflammatory genes, including inducible nitric oxide synthase and interlukin-1β. These results suggest that proteo-stress induced by zerumbone activates HSF1 for exhibiting its anti-inflammatory functions.

Hormonal modulation of the heat shock response: insights from fish with divergent cortisol stress responses

DEFF Research Database (Denmark)

LeBlanc, Sacha; Höglund, Erik; Gilmour, Kathleen M.

2012-01-01

shock response, we capitalized on two lines of rainbow trout specifically bred for their high (HR) and low (LR) cortisol response to stress. We predicted that LR fish, with a low cortisol but high catecholamine response to stress, would induce higher levels of HSPs after acute heat stress than HR trout....... We found that HR fish have significantly higher increases in both catecholamines and cortisol compared with LR fish, and LR fish had no appreciable stress hormone response to heat shock. This unexpected finding prevented further interpretation of the hormonal modulation of the heat shock response...

The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis.

Science.gov (United States)

Dai, Chengkai

2018-01-19

The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSF1-targeting strategies.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'. © 2017 The Author(s).

Shock ignition targets: gain and robustness vs ignition threshold factor

Science.gov (United States)

Atzeni, Stefano; Antonelli, Luca; Schiavi, Angelo; Picone, Silvia; Volponi, Gian Marco; Marocchino, Alberto

2017-10-01

Shock ignition is a laser direct-drive inertial confinement fusion scheme, in which the stages of compression and hot spot formation are partly separated. The hot spot is created at the end of the implosion by a converging shock driven by a final ``spike'' of the laser pulse. Several shock-ignition target concepts have been proposed and relevant gain curves computed (see, e.g.). Here, we consider both pure-DT targets and more facility-relevant targets with plastic ablator. The investigation is conducted with 1D and 2D hydrodynamic simulations. We determine ignition threshold factors ITF's (and their dependence on laser pulse parameters) by means of 1D simulations. 2D simulations indicate that robustness to long-scale perturbations increases with ITF. Gain curves (gain vs laser energy), for different ITF's, are generated using 1D simulations. Work partially supported by Sapienza Project C26A15YTMA, Sapienza 2016 (n. 257584), Eurofusion Project AWP17-ENR-IFE-CEA-01.

Selective activation of human heat shock gene transcription by nitrosourea antitumor drugs mediated by isocyanate-induced damage and activation of heat shock transcription factor.

Science.gov (United States)

Kroes, R A; Abravaya, K; Seidenfeld, J; Morimoto, R I

1991-01-01

Treatment of cultured human tumor cells with the chloroethylnitrosourea antitumor drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) selectively induces transcription and protein synthesis of a subset of the human heat shock or stress-induced genes (HSP90 and HSP70) with little effect on other stress genes or on expression of the c-fos, c-myc, or beta-actin genes. The active component of BCNU and related compounds appears to be the isocyanate moiety that causes carbamoylation of proteins and nucleic acids. Transcriptional activation of the human HSP70 gene by BCNU is dependent on the heat shock element and correlates with the level of heat shock transcription factor and its binding to the heat shock element in vivo. Unlike activation by heat or heavy metals, BCNU-mediated activation is strongly dependent upon new protein synthesis. This suggests that BCNU-induced, isocyanate-mediated damage to newly synthesized protein(s) may be responsible for activation of the heat shock transcription factor and increased transcription of the HSP90 and HSP70 genes. Images PMID:2052560

Hepatic Shock Differential Diagnosis and Risk Factors: A Review Article.

Science.gov (United States)

Soleimanpour, Hassan; Safari, Saeid; Rahmani, Farzad; Nejabatian, Arezu; Alavian, Seyed Moayed

2015-10-01

Liver as an important organ has a vital role in physiological processes in the body. Different causes can disrupt normal function of liver. Factors such as hypo-perfusion, hypoxemia, infections and some others can cause hepatic injury and hepatic shock. Published research resources from 2002 to May 2015 in some databases (PubMed, Scopus, Index Copernicus, DOAJ, EBSCO-CINAHL, Science direct, Cochrane library and Google scholar and Iranian search database like SID and Iranmedex) were investigated for the present study. Different causes can lead to hepatic shock. Most of these causes can be prevented by early resuscitation and treatment of underlying factors. Hepatic shock is detected in ill patients, especially those with hemodynamic disorders. It can be prevented by early treatment of underlying disease. There is no definite treatment for hepatic shock and should be managed conservatively. Hepatic shock in patients can increase the mortality rate.

Heat shock modulates the subcellular localization, stability, and activity of HIPK2

International Nuclear Information System (INIS)

Upadhyay, Mamta; Bhadauriya, Pratibha; Ganesh, Subramaniam

2016-01-01

The homeodomain-interacting protein kinase-2 (HIPK2) is a highly conserved serine/threonine kinase and is involved in transcriptional regulation. HIPK2 is a highly unstable protein, and is kept at a low level under normal physiological conditions. However, exposure of cells to physiological stress – such as hypoxia, oxidative stress, or UV damage – is known to stabilize HIPK2, leading to the HIPK2-dependent activation of p53 and the cell death pathway. Therefore HIPK2 is also known as a stress kinase and as a stress-activated pro-apoptotic factor. We demonstrate here that exposure of cells to heat shock results in the stabilization of HIPK2 and the stabilization is mediated via K63-linked ubiquitination. Intriguingly, a sub-lethal heat shock (42 °C, 1 h) results in the cytoplasmic localization of HIPK2, while a lethal heat shock (45 °C, 1 h) results in its nuclear localization. Cells exposed to the lethal heat shock showed significantly higher levels of the p53 activity than those exposed to the sub-lethal thermal stress, suggesting that both the level and the nuclear localization are essential for the pro-apoptotic activity of HIPK2 and that the lethal heat shock could retain the HIPK2 in the nucleus to promote the cell death. Taken together our study underscores the importance of HIPK2 in stress mediated cell death, and that the HIPK2 is a generic stress kinase that gets activated by diverse set of physiological stressors.

Heat shock modulates the subcellular localization, stability, and activity of HIPK2

Energy Technology Data Exchange (ETDEWEB)

Upadhyay, Mamta; Bhadauriya, Pratibha; Ganesh, Subramaniam, E-mail: sganesh@iitk.ac.in

2016-04-15

The homeodomain-interacting protein kinase-2 (HIPK2) is a highly conserved serine/threonine kinase and is involved in transcriptional regulation. HIPK2 is a highly unstable protein, and is kept at a low level under normal physiological conditions. However, exposure of cells to physiological stress – such as hypoxia, oxidative stress, or UV damage – is known to stabilize HIPK2, leading to the HIPK2-dependent activation of p53 and the cell death pathway. Therefore HIPK2 is also known as a stress kinase and as a stress-activated pro-apoptotic factor. We demonstrate here that exposure of cells to heat shock results in the stabilization of HIPK2 and the stabilization is mediated via K63-linked ubiquitination. Intriguingly, a sub-lethal heat shock (42 °C, 1 h) results in the cytoplasmic localization of HIPK2, while a lethal heat shock (45 °C, 1 h) results in its nuclear localization. Cells exposed to the lethal heat shock showed significantly higher levels of the p53 activity than those exposed to the sub-lethal thermal stress, suggesting that both the level and the nuclear localization are essential for the pro-apoptotic activity of HIPK2 and that the lethal heat shock could retain the HIPK2 in the nucleus to promote the cell death. Taken together our study underscores the importance of HIPK2 in stress mediated cell death, and that the HIPK2 is a generic stress kinase that gets activated by diverse set of physiological stressors.

HSF1 and HSF3 cooperatively regulate the heat shock response in lizards.

Science.gov (United States)

Takii, Ryosuke; Fujimoto, Mitsuaki; Matsuura, Yuki; Wu, Fangxu; Oshibe, Namiko; Takaki, Eiichi; Katiyar, Arpit; Akashi, Hiroshi; Makino, Takashi; Kawata, Masakado; Nakai, Akira

2017-01-01

Cells cope with temperature elevations, which cause protein misfolding, by expressing heat shock proteins (HSPs). This adaptive response is called the heat shock response (HSR), and it is regulated mainly by heat shock transcription factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master regulator of HSP expression during proteotoxic stress including heat shock in mammals, whereas HSF3 is required for the HSR in birds. To examine whether only one of the HSF family members possesses the potential to induce the HSR in vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes. The reconstructed phylogenetic tree of vertebrate HSFs demonstrated that HSF3 in one species is unrelated with that in other species. We found that the DNA-binding activity of both HSF1 and HSF3 in lizard and frog cells was induced in response to heat shock. Unexpectedly, overexpression of lizard and frog HSF3 as well as HSF1 induced HSP70 expression in mouse cells during heat shock, indicating that the two factors have the potential to induce the HSR. Furthermore, knockdown of either HSF3 or HSF1 markedly reduced HSP70 induction in lizard cells and resistance to heat shock. These results demonstrated that HSF1 and HSF3 cooperatively regulate the HSR at least in lizards, and suggest complex mechanisms of the HSR in lizards as well as frogs.

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

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Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

2016-07-15

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Cosmic-ray acceleration at stellar wind terminal shocks

International Nuclear Information System (INIS)

Webb, G.M.; Forman, M.A.; Axford, W.I.

1985-01-01

Steady-state, spherically symmetric, analytic solutions of the cosmic-ray transport equations, applicable to the problem of acceleration of cosmic rays at the terminal shock to a stellar wind, are studied. The spectra, gradients, and flow patterns of particle modulated and accelerated by the stellar wind and shock are investigated by means of monoenergetic-source solutions at finite radius, as well as solutions with monoenergetic and power-law Galactic spectra. The solutions obtained apply in the test particle limit in which the cosmic rays do not modify the background flow. The solutions show a characteristic power-law momentum spectrum for accelerated particles and a more complex spectrum of particles that are decelerated in the stellar wind. The power-law spectral index depends on the compression ratio of the shock and on the modulation parameters characterizing propagation conditions in the upstream and downstream regions of the shock. Solutions of the transport equations for the total density N (integrated over all energies), pressure P/sub c/, and energy flux F/sub c/ of Galactic cosmic rays interacting with a stellar wind and shock are also studied. The density N(r) increases with radius r, and for strong shocks with large enough modulation parameters, there may be a significant enhancement of the pressure of weakly relativistic particles near the shock compared to the cosmic-ray background pressure P/sub infinity/. The emergent energy flux at infinity is of the order of 4π R 2 V 1 P/sub infinity/ (V 1 is wind velocity upstream of the shock, R is shock radius)

A novel fluid resuscitation strategy modulates pulmonary transcription factor activation in a murine model of hemorrhagic shock

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Todd W. Costantini

2010-01-01

Full Text Available INTRODUCTION: Combining the hemodynamic and immune benefits of hypertonic saline with the anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline (HSPTX as a hemorrhagic shock resuscitation strategy reduces lung injury when compared with the effects of Ringer's lactate (RL. We hypothesized that HSPTX exerts its anti-inflammatory effects by interfering with nuclear factor kappa B/cAMP response element-binding protein (NF-κB-CREB competition for the coactivator CREB-binding protein (CBP in lung tissue, thus affecting pro-inflammatory mediator production. METHODS: Male Sprague-Dawley rats underwent 60 minutes of hemorrhagic shock to reach a mean arterial blood pressure of 35 mmHg followed by resuscitation with either RL or HSPTX (7.5% HS + 25 mg/kg PTX. After four hours, lung samples were collected. NF-κB activation was assessed by measuring the levels of phosphorylated cytoplasmic inhibitor of kappa B (I-κB and nuclear NF-κB p65 by western blot. NF-κB and CREB DNA-binding activity were measured by electrophoretic mobility shift assay (EMSA. Competition between NF-κB and CREB for the coactivator CBP was determined by immunoprecipitation. Interleukin-8 (IL-8 levels in the lung were measured by ELISA. RESULTS: RL resuscitation produced significantly higher levels of lung IL-8 levels, I-κB phosphorylation, p65 phosphorylation, and NF-κB DNA binding compared with HSPTX. NF-κB-CBP-binding activity was similar in both groups, whereas CREB-CBP-binding activity was significantly increased with HSPTX. CREB-DNA binding-activity increased to a greater level with HSPTX compared with RL. DISCUSSION: HSPTX decreases lung inflammation following hemorrhagic shock compared with conventional resuscitation using RL through attenuation of NF-κB signaling and increased CREB-DNA binding activity. HSPTX may have therapeutic potential in the attenuation of ischemia-reperfusion injury observed after severe hemorrhagic shock.

Heat Shock Factor 1 Depletion Sensitizes A172 Glioblastoma Cells to Temozolomide via Suppression of Cancer Stem Cell-Like Properties

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Chang-Nim Im

2017-02-01

Full Text Available Heat shock factor 1 (HSF1, a transcription factor activated by various stressors, regulates proliferation and apoptosis by inducing expression of target genes, such as heat shock proteins and Bcl-2 (B-cell lymphoma 2 interacting cell death suppressor (BIS. HSF1 also directly interacts with BIS, although it is still unclear whether this interaction is critical in the regulation of glioblastoma stem cells (GSCs. In this study, we examined whether small interfering RNA-mediated BIS knockdown decreased protein levels of HSF1 and subsequent nuclear localization under GSC-like sphere (SP-forming conditions. Consistent with BIS depletion, HSF1 knockdown also reduced sex determining region Y (SRY-box 2 (SOX2 expression, a marker of stemness, accompanying the decrease in SP-forming ability and matrix metalloprotease 2 (MMP2 activity. When HSF1 or BIS knockdown was combined with temozolomide (TMZ treatment, a standard drug used in glioblastoma therapy, apoptosis increased, as measured by an increase in poly (ADP-ribose polymerase (PARP cleavage, whereas cancer stem-like properties, such as colony-forming activity and SOX2 protein expression, decreased. Taken together, our findings suggest that targeting BIS or HSF1 could be a viable therapeutic strategy for GSCs resistant to conventional TMZ treatment.

Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans

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Heintz, Caroline; Doktor, Thomas K; Lanjuin, Anne

2017-01-01

via splicing factor 1 (SFA-1; the C. elegans homologue of SF1, also known as branchpoint binding protein, BBP). We show that SFA-1 is specifically required for lifespan extension by dietary restriction and by modulation of the TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 kinase. We also...... homeostasis is a biomarker and predictor of life expectancy in Caenorhabditis elegans. Using transcriptomics and in-depth splicing analysis in young and old animals fed ad libitum or subjected to dietary restriction, we find defects in global pre-mRNA splicing with age that are reduced by dietary restriction...

Numerical evaluation of stress intensity factor for vessel and pipe subjected to thermal shock

International Nuclear Information System (INIS)

Kim, Y.W.; Lee, H.Y.; Yoo, B.

1994-01-01

The thermal weight function method and the finite element method were employed in the numerical computation of the stress intensity factor for a cracked vessel and the cracked pipe subjected to thermal shock. A wall subjected to thermal shock was analyzed, and it has been shown that the effect of thermal shock on the stress intensity factor is dominant for the crack with small crack length to thickness ratio. Convection at the crack face had an influence on the stress intensity factor in the early stage of thermal shock. (Author)

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

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Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

2010-09-01

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

One-chip Integrated Module of MEMS Shock Sensor and Sensing Amplifier LSI using Pseudo-SOC Technology

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Iida, Atsuko; Onozuka, Yutaka; Nishigaki, Michihiko; Yamada, Hiroshi; Funaki, Hideyuki; Itaya, Kazuhiko

We have been developing the pseudo-SOC technology for one-chip module integration of heterogeneous devices that realizes high electrical performance and high density of devices embodying the advantages of both SOC technology and SIP technology. Especially, this technology is available for MEMS-LSI integration. We developed a 0.2mm-thickness one-chip module integrating a MEMS shock sensor and a sensing amplifier LSI by applying this technology. The MEMS shock sensor and the sensing amplifier LSI were connected by high-rigidity epoxy resin optimized the material constants to reduce the stress and the warpage resulting from resin shrinkage due to curing. Then the planar insulating layer and the redistributed conducting layer were formed on it for the global layer. The MEMS shock sensor was preformed to be modularized with a glass cap. Electrical contacts were achieved by bonding of Au bumps on the MEMS fixed electrodes and via holes filled with Ag paste of the glass cap. Functional performance was confirmed by obtaining signal corresponding to the reference signal of the pick-up sensor. Furthermore, stress analysis was performed using the FEM model simulation considering the resin shrinkage.

Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock.

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Wu, Feng; Peng, Zhanglong; Park, Pyong Woo; Kozar, Rosemary A

2017-09-01

Syndecan-1 (Sdc1) is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding of Sdc1 deleterious. Resuscitation with fresh frozen plasma (FFP) has been correlated with restitution of pulmonary Sdc1 and reduction of lung injury, but the precise contribution of Sdc1 to FFPs protection in the lung remains unclear. Human lung endothelial cells were used to assess the time and dose-dependent effect of FFP on Sdc1 expression and the effect of Sdc1 silencing on in vitro endothelial cell permeability and actin stress fiber formation. Wild-type and Sdc1 mice were subjected to hemorrhagic shock followed by resuscitation with lactated Ringers (LR) or FFP and compared with shock alone and shams. Lungs were harvested after 3 h for analysis of permeability, histology, and inflammation and for measurement of syndecan- 2 and 4 expression. In vitro, FFP enhanced pulmonary endothelial Sdc1 expression in time- and dose-dependent manners and loss of Sdc1 in pulmonary endothelial cells worsened permeability and stress fiber formation by FFP. Loss of Sdc1 in vivo led to equivalency between LR and FFP in restoring pulmonary injury, inflammation, and permeability after shock. Lastly, Sdc1 mice demonstrated a significant increase in pulmonary syndecan 4 expression after hemorrhagic shock and FFP-based resuscitation. Taken together, our findings support a key role for Sdc1 in modulating pulmonary protection by FFP after hemorrhagic shock. Our results also suggest that other members of the syndecan family may at least be contributing to FFP's effects on the endothelium, an area that warrants further investigation.

Analysis of transactivation potential of rice (Oryza sativa L.) heat shock factors.

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Lavania, Dhruv; Dhingra, Anuradha; Grover, Anil

2018-06-01

Based on yeast one-hybrid assays, we show that the presence of C-terminal AHA motifs is not a prerequisite for transactivation potential in rice heat shock factors. Transcriptional activation or transactivation (TA) of heat stress responsive genes takes place by binding of heat shock factors (Hsfs) to heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.) Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5, A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of TA potential of the OsHsf family (comprising of 25 members) emerging from this study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076-3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b, A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a, A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3 and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a, A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not analyzed). Thus, the presence or absence of AHA motif is possibly not the only factor determining TA potential of OsHsfs. Our findings will help to identify the transcriptional activators of rice heat shock response.

Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

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Hidekazu Kuwayama

Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

Deteriorated stress response in stationary-phase yeast: Sir2 and Yap1 are essential for Hsf1 activation by heat shock and oxidative stress, respectively.

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Inbal Nussbaum

Full Text Available Stationary-phase cultures have been used as an important model of aging, a complex process involving multiple pathways and signaling networks. However, the molecular processes underlying stress response of non-dividing cells are poorly understood, although deteriorated stress response is one of the hallmarks of aging. The budding yeast Saccharomyces cerevisiae is a valuable model organism to study the genetics of aging, because yeast ages within days and are amenable to genetic manipulations. As a unicellular organism, yeast has evolved robust systems to respond to environmental challenges. This response is orchestrated largely by the conserved transcription factor Hsf1, which in S. cerevisiae regulates expression of multiple genes in response to diverse stresses. Here we demonstrate that Hsf1 response to heat shock and oxidative stress deteriorates during yeast transition from exponential growth to stationary-phase, whereas Hsf1 activation by glucose starvation is maintained. Overexpressing Hsf1 does not significantly improve heat shock response, indicating that Hsf1 dwindling is not the major cause for Hsf1 attenuated response in stationary-phase yeast. Rather, factors that participate in Hsf1 activation appear to be compromised. We uncover two factors, Yap1 and Sir2, which discretely function in Hsf1 activation by oxidative stress and heat shock. In Δyap1 mutant, Hsf1 does not respond to oxidative stress, while in Δsir2 mutant, Hsf1 does not respond to heat shock. Moreover, excess Sir2 mimics the heat shock response. This role of the NAD+-dependent Sir2 is supported by our finding that supplementing NAD+ precursors improves Hsf1 heat shock response in stationary-phase yeast, especially when combined with expression of excess Sir2. Finally, the combination of excess Hsf1, excess Sir2 and NAD+ precursors rejuvenates the heat shock response.

Deteriorated stress response in stationary-phase yeast: Sir2 and Yap1 are essential for Hsf1 activation by heat shock and oxidative stress, respectively.

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Nussbaum, Inbal; Weindling, Esther; Jubran, Ritta; Cohen, Aviv; Bar-Nun, Shoshana

2014-01-01

Stationary-phase cultures have been used as an important model of aging, a complex process involving multiple pathways and signaling networks. However, the molecular processes underlying stress response of non-dividing cells are poorly understood, although deteriorated stress response is one of the hallmarks of aging. The budding yeast Saccharomyces cerevisiae is a valuable model organism to study the genetics of aging, because yeast ages within days and are amenable to genetic manipulations. As a unicellular organism, yeast has evolved robust systems to respond to environmental challenges. This response is orchestrated largely by the conserved transcription factor Hsf1, which in S. cerevisiae regulates expression of multiple genes in response to diverse stresses. Here we demonstrate that Hsf1 response to heat shock and oxidative stress deteriorates during yeast transition from exponential growth to stationary-phase, whereas Hsf1 activation by glucose starvation is maintained. Overexpressing Hsf1 does not significantly improve heat shock response, indicating that Hsf1 dwindling is not the major cause for Hsf1 attenuated response in stationary-phase yeast. Rather, factors that participate in Hsf1 activation appear to be compromised. We uncover two factors, Yap1 and Sir2, which discretely function in Hsf1 activation by oxidative stress and heat shock. In Δyap1 mutant, Hsf1 does not respond to oxidative stress, while in Δsir2 mutant, Hsf1 does not respond to heat shock. Moreover, excess Sir2 mimics the heat shock response. This role of the NAD+-dependent Sir2 is supported by our finding that supplementing NAD+ precursors improves Hsf1 heat shock response in stationary-phase yeast, especially when combined with expression of excess Sir2. Finally, the combination of excess Hsf1, excess Sir2 and NAD+ precursors rejuvenates the heat shock response.

Analytic study of 1D diffusive relativistic shock acceleration

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Keshet, Uri, E-mail: ukeshet@bgu.ac.il [Physics Department, Ben-Gurion University of the Negev, POB 653, Be' er-Sheva 84105 (Israel)

2017-10-01

Diffusive shock acceleration (DSA) by relativistic shocks is thought to generate the dN / dE ∝ E{sup −p} spectra of charged particles in various astronomical relativistic flows. We show that for test particles in one dimension (1D), p {sup −1}=1−ln[γ{sub d}(1+β{sub d})]/ln[γ{sub u}(1+β{sub u})], where β{sub u}(β{sub d}) is the upstream (downstream) normalized velocity, and γ is the respective Lorentz factor. This analytically captures the main properties of relativistic DSA in higher dimensions, with no assumptions on the diffusion mechanism. Unlike 2D and 3D, here the spectrum is sensitive to the equation of state even in the ultra-relativistic limit, and (for a J(üttner-Synge equation of state) noticeably hardens with increasing 1<γ{sub u}<57, before logarithmically converging back to p (γ{sub u→∞})=2. The 1D spectrum is sensitive to drifts, but only in the downstream, and not in the ultra-relativistic limit.

Heat shock-induced accumulation of translation elongation and termination factors precedes assembly of stress granules in S. cerevisiae.

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Tomas Grousl

Full Text Available In response to severe environmental stresses eukaryotic cells shut down translation and accumulate components of the translational machinery in stress granules (SGs. Since they contain mainly mRNA, translation initiation factors and 40S ribosomal subunits, they have been referred to as dominant accumulations of stalled translation preinitiation complexes. Here we present evidence that the robust heat shock-induced SGs of S. cerevisiae also contain translation elongation factors eEF3 (Yef3p and eEF1Bγ2 (Tef4p as well as translation termination factors eRF1 (Sup45p and eRF3 (Sup35p. Despite the presence of the yeast prion protein Sup35 in heat shock-induced SGs, we found out that its prion-like domain is not involved in the SGs assembly. Factors eEF3, eEF1Bγ2 and eRF1 were accumulated and co-localized with Dcp2 foci even upon a milder heat shock at 42°C independently of P-bodies scaffolding proteins. We also show that eEF3 accumulations at 42°C determine sites of the genuine SGs assembly at 46°C. We suggest that identification of translation elongation and termination factors in SGs might help to understand the mechanism of the eIF2α factor phosphorylation-independent repression of translation and SGs assembly.

Mediator Recruitment to Heat Shock Genes Requires Dual Hsf1 Activation Domains and Mediator Tail Subunits Med15 and Med16*

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Kim, Sunyoung; Gross, David S.

2013-01-01

The evolutionarily conserved Mediator complex is central to the regulation of gene transcription in eukaryotes because it serves as a physical and functional interface between upstream regulators and the Pol II transcriptional machinery. Nonetheless, its role appears to be context-dependent, and the detailed mechanism by which it governs the expression of most genes remains unknown. Here we investigate Mediator involvement in HSP (heat shock protein) gene regulation in the yeast Saccharomyces cerevisiae. We find that in response to thermal upshift, subunits representative of each of the four Mediator modules (Head, Middle, Tail, and Kinase) are rapidly, robustly, and selectively recruited to the promoter regions of HSP genes. Their residence is transient, returning to near-background levels within 90 min. Hsf1 (heat shock factor 1) plays a central role in recruiting Mediator, as indicated by the fact that truncation of either its N- or C-terminal activation domain significantly reduces Mediator occupancy, whereas removal of both activation domains abolishes it. Likewise, ablation of either of two Mediator Tail subunits, Med15 or Med16, reduces Mediator recruitment to HSP promoters, whereas deletion of both abolishes it. Accompanying the loss of Mediator, recruitment of RNA polymerase II is substantially diminished. Interestingly, Mediator antagonizes Hsf1 occupancy of non-induced promoters yet facilitates enhanced Hsf1 association with activated ones. Collectively, our observations indicate that Hsf1, via its dual activation domains, recruits holo-Mediator to HSP promoters in response to acute heat stress through cooperative physical and/or functional interactions with the Tail module. PMID:23447536

A Prognostic Model for Development of Profound Shock among Children Presenting with Dengue Shock Syndrome.

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Phung Khanh Lam

Full Text Available To identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS.We analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was "profound DSS", defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock, or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock, and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches.The analysis population included 1207 children of whom 222 (18% progressed to "profound DSS" and 433 (36% had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for "profound DSS" showed acceptable discrimination (AUC=0.69 for internal validation and calibration and is presented as a simple score-chart.Several risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas.

Corticosteroids in the treatment of dengue shock syndrome

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Rajapakse S

2014-05-01

Full Text Available Senaka Rajapakse,1 Chaturaka Rodrigo,1 Sachith Maduranga,1 Anoja Chamarie Rajapakse21Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka; 2Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Sutton-in-Ashfield, Nottinghamshire, UKAbstract: Dengue infection causes significant morbidity and mortality in over 100 countries worldwide, and its incidence is on the rise. The pathophysiological basis for the development of severe dengue, characterized by plasma leakage and the “shock syndrome” are poorly understood. No specific treatment or vaccine is available, and careful monitoring and judicious administration of fluids forms the mainstay of management at present. It is postulated that vascular endothelial dysfunction, induced by cytokine and chemical mediators, is an important mechanism of plasma leakage. Although corticosteroids are potent modulators of the immune system, their role in pharmacological doses in modulating the purported immunological effects that take place in severe dengue has been a subject of controversy. The key evidence related to the role of corticosteroids for various manifestations of dengue are reviewed here. In summary, there is currently no high-quality evidence supporting the beneficial effects of corticosteroids for treatment of shock, prevention of serious complications, or increasing platelet counts. Non-randomized trials of corticosteroids given as rescue medication for severe shock have shown possible benefit. Nonetheless, the evidence base is small, and good-quality trials are lacking. We reiterate the need for well-designed and adequately powered randomized controlled trials of corticosteroids for the treatment of dengue shock.Keywords: dengue, dengue shock, shock, corticosteroids, vascular leak, thrombocytopenia

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

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Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur

2012-01-01

Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

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Martina Kalle

Full Text Available Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

Riboflavin protects mice against liposaccharide-induced shock through expression of heat shock protein 25

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Riboflavin (vitamin B2) is a water-soluble vitamin essential for normal cellular functions, growth and development. The study was aimed at investigating the effects of vitamin B2 on the survival rate, and expressions of tissue heat shock protein 25 (HSP25) and heat shock factor 1 (HSF1) in mice und...

Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

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Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

2009-07-01

We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

Effect of Geranylgeranylacetone on Ultraviolet Radiation Type B-Induced Cataract in Heat-Shock Transcription Factor 1 Heterozygous Mouse.

Science.gov (United States)

Ogasawara, Satoshi; Hashizume, Kouhei; Okuno, Takashi; Imaizumi, Toshiyasu; Inomata, Yui; Tezuka, Yu; Sanbe, Atushi; Kurosaka, Daijiro

2017-05-01

We investigated whether heat-shock transcription factor 1 (HSF1) was involved in ultraviolet radiation type B (UVR-B)-induced lens opacity (cataract) using HSF1 heterozygous mice. We also examined the effects of geranylgeranylacetone (GGA), an inducer of heat-shock proteins via activation of HSF, on the UVR-B-induced cataract. Male HSF1 +/- and WT mice were unilaterally exposed to UVR-B (total: 1200mJ) at 16 weeks of age. At 48 h after the last UVR-B irradiation, the lens was isolated and the induction of the cataract was quantified as the cataract area ratio (opacity area/anterior capsule). GGA was orally administered at a dosage of 500 mg/kg once a day for two days before the first UVR-B exposure until the end of the experiment (21days in total). The HSF1 expression was more greatly decreased in the lens from HSF1 +/- mice than in that from WT mice (p B exposure could mainly induce cataracts in the anterior capsule in both HSF1 +/- and WT mice, while the opacity of the lens was markedly enhanced in HSF 1+/- mice compared to that in WT mice(p (0.01). GGA treatment could prevent the induction of lens opacity by UVR-B exposure in both WT and HSF1 +/- mice as compared with the non-administration group (p B radiation was seen in lens protein levels of αA-crystallin, αB-crystallin, or γ-crystallin with or without GGA administration among all groups of mice. In contrast to the crystallins, the lens protein level of HSP25 was decreased by UVR-B exposure in both HSF1 +/- and WT mice, and was significantly recovered in WT mice by the GGA treatment (p B-induced cataracts, possibly via regulation of HSPs such as HSP25.

pH Modulates the Binding of EGR1 Transcription Factor to DNA

Science.gov (United States)

Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

2013-01-01

EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice.

Science.gov (United States)

Ohno, Y; Egawa, T; Yokoyama, S; Nakai, A; Sugiura, T; Ohira, Y; Yoshioka, T; Goto, K

2015-12-01

Effects of heat shock transcription factor 1 (HSF1) deficiency on heat stress-associated increase in slow soleus muscle mass of mice were investigated. Both HSF1-null and wild-type mice were randomly assigned to control and heat-stressed groups. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anaesthesia. Significant increase in wet and dry weights, and protein content of soleus muscle in wild-type mice was observed seven days after the application of the heat stress. However, heat stress had no impact on soleus muscle mass in HSF1-null mice. Neither type of mice exhibited much effect of heat stress on HSF mRNA expression (HSF1, HSF2 and HSF4). On the other hand, heat stress upregulated heat shock proteins (HSPs) at the mRNA (HSP72) and protein (HSP72 and HSP110) levels in wild-type mice, but not in HSF1-null mice. The population of Pax7-positive nuclei relative to total myonuclei of soleus muscle in wild-type mice was significantly increased by heat stress, but not in HSF1-null mice. Furthermore, the absence of HSF1 gene suppressed heat stress-associated phosphorylation of Akt and p70 S6 kinase (p-p70S6K) in soleus muscle. Heat stress-associated increase in skeletal muscle mass may be induced by HSF1 and/or HSF1-mediated stress response that activates muscle satellite cells and Akt/p70S6K signalling pathway. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Heat shock factors HsfB1 and HsfB2b are involved in the regulation of Pdf1.2 expression and pathogen resistance in Arabidopsis.

Science.gov (United States)

Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

2009-01-01

In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses.

Reactive oxygen species (ROS) and the heat stress response of Daphnia pulex: ROS-mediated activation of hypoxia-inducible factor 1 (HIF-1) and heat shock factor 1 (HSF-1) and the clustered expression of stress genes.

Science.gov (United States)

Klumpen, Eva; Hoffschröer, Nadine; Zeis, Bettina; Gigengack, Ulrike; Dohmen, Elias; Paul, Rüdiger J

2017-01-01

Heat stress in ectotherms involves direct (e.g. protein damage) and/or indirect effects (temperature-induced hypoxia and ROS formation), which cause activation of the transcription factors (TF) heat shock factor 1 (HSF-1) and/or hypoxia-inducible factor 1 (HIF-1). The present study focused on the links between stress (ROS) signals, nuclear (n) and cytoplasmic (c) HSF-1/HIF-1 levels, and stress gene expression on mRNA and protein levels (e.g. heat-shock protein 90, HSP90) upon acute heat and ROS (H 2 O 2 ) stress. Acute heat stress (30°C) evoked fluctuations in ROS level. Different feeding regimens, which affected the glutathione (GSH) level, allowed altering the frequency of ROS fluctuations. Other data showed fluctuation frequency to depend also on ROS production rate. The heat-induced slow or fast ROS fluctuations (at high or low GSH levels) evoked slow or fast fluctuations in the levels of nHIF-1α, nHSF-1 and gene products (mRNAs and protein), albeit after different time delays. Time delays to ROS fluctuations were, for example,shorter for nHIF-1α than for nHSF-1 fluctuations, and nHIF-1α fluctuations preceded and nHSF-1 fluctuations followed fluctuations in HSP90 mRNA level. Cytoplasmic TF levels either changed little (cHIF-1α) or showed a steady increase (cHSF-1). Applying acute H 2 O 2 stress (at 20°C) revealed effects on nHIF-1α and mRNA levels, but no significant effects on nHSF-1 level. Transcriptome data additionally showed coordinated fluctuations of mRNA levels upon acute heat stress, involving mRNAs for HSPs and other stress proteins, with all corresponding genes carrying DNA binding motifs for HIF-1 and HSF-1. This study provided evidence for promoting effects of ROS and HIF-1 on early haemoglobin, HIF-1α and HSP90 mRNA expressions upon heat or ROS stress. The increasing cHSF-1 level likely affected nHSF-1 level and later HSP90 mRNA expression. Heat stress evoked ROS fluctuations, with this stress signal forwarded via nHIF-1 and nHSF-1

Shock and Vibration. Volume 1, Issue 1

National Research Council Canada - National Science Library

Pilkey, Walter D

1994-01-01

..., and earthquake engineering. Among the specific areas to be covered are vibration testing and control, vibration condition monitoring and diagnostics, shock hardenings, modal technology, shock testing, data acquisition, fluid...

MHD intermediate shock discontinuities: Pt. 1

International Nuclear Information System (INIS)

Kennel, C.F.; Blandford, R.D.; Coppi, P.

1989-01-01

Recent numerical investigations have focused attention once more on the role of intermediate shocks in MHD. Four types of intermediate shock are identified using a graphical representation of the MHD Rankine-Hugoniot conditions. This same representation can be used to exhibit the close relationship of intermediate shocks to switch-on shocks and rotational discontinuities. The conditions under which intermediate discontinuities can be found are elucidated. The variations in velocity, pressure, entropy and magnetic-field jumps with upstream parameters in intermediate shocks are exhibited graphically. The evolutionary arguments traditionally advanced against intermediate shocks may fail because the equations of classical MHD are not strictly hyperbolic. (author)

Equation-of-state dependent features in shock-oscillation modulated neutrino and gravitational-wave signals from supernovae

Science.gov (United States)

Marek, A.; Janka, H.-T.; Müller, E.

2009-03-01

We present two-dimensional (axisymmetric) neutrino-hydrodynamic simulations of the long-time accretion phase of a 15 M_⊙ progenitor star after core bounce and before the launch of a supernova explosion, when non-radial hydrodynamic instabilities like convection occur in different regions of the collapsing stellar core and the standing accretion shock instability (SASI) leads to large-amplitude oscillations of the stalled shock with a period of tens of milliseconds. Our simulations were performed with the Prometheus-Vertex code, which includes a multi-flavor, energy-dependent neutrino transport scheme and employs an effective relativistic gravitational potential. Testing the influence of a stiff and a soft equation of state for hot neutron star matter, we find that the non-radial mass motions in the supernova core impose a time variability on the neutrino and gravitational-wave signals with larger amplitudes, as well as higher frequencies in the case of a more compact nascent neutron star. After the prompt shock-breakout burst of electron neutrinos, a more compact accreting remnant produces higher neutrino luminosities and higher mean neutrino energies. The observable neutrino emission in the SASI sloshing direction exhibits a modulation of several ten percent in the luminosities and around 1 MeV in the mean energies with most power at typical SASI frequencies between roughly 20 and 100 Hz. The modulation is caused by quasi-periodic variations in the mass accretion rate of the neutron star in each hemisphere. At times later than ~50-100 ms after bounce, the gravitational-wave amplitude is dominated by the growing low-frequency (⪉200 Hz) signal associated with anisotropic neutrino emission. A high-frequency wave signal results from nonradial gas flows in the outer layers of the anisotropically accreting neutron star. Right after bounce such nonradial mass motions occur due to prompt post-shock convection in both considered cases and contribute mostly to the early

Cold shock protein YB-1 is involved in hypoxia-dependent gene transcription

International Nuclear Information System (INIS)

Rauen, Thomas; Frye, Bjoern C.; Wang, Jialin; Raffetseder, Ute; Alidousty, Christina; En-Nia, Abdelaziz; Floege, Jürgen; Mertens, Peter R.

2016-01-01

Hypoxia-dependent gene regulation is largely orchestrated by hypoxia-inducible factors (HIFs), which associate with defined nucleotide sequences of hypoxia-responsive elements (HREs). Comparison of the regulatory HRE within the 3′ enhancer of the human erythropoietin (EPO) gene with known binding motifs for cold shock protein Y-box (YB) protein-1 yielded strong similarities within the Y-box element and 3′ adjacent sequences. DNA binding assays confirmed YB-1 binding to both, single- and double-stranded HRE templates. Under hypoxia, we observed nuclear shuttling of YB-1 and co-immunoprecipitation assays demonstrated that YB-1 and HIF-1α physically interact with each other. Cellular YB-1 depletion using siRNA significantly induced hypoxia-dependent EPO production at both, promoter and mRNA level. Vice versa, overexpressed YB-1 significantly reduced EPO-HRE-dependent gene transcription, whereas this effect was minor under normoxia. HIF-1α overexpression induced hypoxia-dependent gene transcription through the same element and accordingly, co-expression with YB-1 reduced HIF-1α-mediated EPO induction under hypoxic conditions. Taken together, we identified YB-1 as a novel binding factor for HREs that participates in fine-tuning of the hypoxia transcriptome. - Highlights: • Hypoxia drives nuclear translocation of cold shock protein YB-1. • YB-1 physically interacts with hypoxia-inducible factor (HIF)-1α. • YB-1 binds to the hypoxia-responsive element (HRE) within the erythropoietin (EPO) 3′ enhancer. • YB-1 trans-regulates transcription of hypoxia-dependent genes such as EPO and VEGF.

Factors influencing radiation exposure during the extracorporeal shock wave lithotripsy

Energy Technology Data Exchange (ETDEWEB)

Wei Chuan Chen; Ying Huei Lee; Ming Tsun Chen; Jong Khing Huang; Luke S Chang (Division of Urology, Dept. of Surgery, National Yang-Ming Medical College and Veterans General Hospital-Taipei, Taiwan (China))

1991-01-01

A prospective evaluation of 89 consecutive sessions of extracorporeal shock wave lithotripsy (ESWL) was undertaken to try and find the best way of minimising the amount of exposure to radiation. Forty-two patients were randomly allocated to undergo ESWL treatment by experienced surgeons (group A), and 47 to undergo the treatment by inexperienced surgeons (group B). The mean calculated entrance radiation exposure was 3.01 rads (group A: 2.64 (0.97) rads, range 1.00-4.48, group B: 3.38 (0.86) rads, range 1.11-5.75). Among factors that influenced radiation exposure, the tissue: air ratio should be borne in mind and the level of skill in controlling movement of gantry was the most important in reducing the exposure to radiation. (au).

Factors influencing radiation exposure during the extracorporeal shock wave lithotripsy

International Nuclear Information System (INIS)

Wei Chuan Chen; Ying Huei Lee; Ming Tsun Chen; Jong Khing Huang; Luke S Chang

1991-01-01

A prospective evaluation of 89 consecutive sessions of extracorporeal shock wave lithotripsy (ESWL) was undertaken to try and find the best way of minimising the amount of exposure to radiation. Forty-two patients were randomly allocated to undergo ESWL treatment by experienced surgeons (group A), and 47 to undergo the treatment by inexperienced surgeons (group B). The mean calculated entrance radiation exposure was 3.01 rads (group A: 2.64 (0.97) rads, range 1.00-4.48, group B: 3.38 (0.86) rads, range 1.11-5.75). Among factors that influenced radiation exposure, the tissue: air ratio should be borne in mind and the level of skill in controlling movement of gantry was the most important in reducing the exposure to radiation. (au)

Shock equation of state of 6LiH to 1.1 TPa

Science.gov (United States)

Lazicki, A.; London, R. A.; Coppari, F.; Erskine, D.; Whitley, H. D.; Caspersen, K. J.; Fratanduono, D. E.; Morales, M. A.; Celliers, P. M.; Eggert, J. H.; Millot, M.; Swift, D. C.; Collins, G. W.; Kucheyev, S. O.; Castor, J. I.; Nilsen, J.

2017-10-01

Using laser-generated shock waves, we have measured pressure, density, and temperature of LiH on the principal Hugoniot between 260 and 1100 GPa (2.6-11 Mbar) and on a second-shock Hugoniot up to 1400 GPa to near fivefold compression, extending the maximum pressure reached in non-nuclear experiments by a factor of two. We observe the onset of metal-like reflectivity consistent with temperature-induced ionization of the Li 2s electron, and no sign of additional changes in ionization up to the maximum pressure. Our measurements are in good agreement with gas gun, Z-machine, and underground test data and are accurately described by quantum molecular dynamics simulations. The results confirm the validity of equation of state models built on an average-atom description of the electron-thermal contribution to the free energy and a density-dependent Grüneisen parameter to describe shock response of LiH over this pressure range.

Experimental Study of the Effect of Water Mist Location On Blast Overpressure Attenuation in A Shock Tube

Science.gov (United States)

Mataradze, Edgar; Chikhradze, Nikoloz; Bochorishvili, Nika; Akhvlediani, Irakli; Tatishvili, Dimitri

2017-12-01

Explosion protection technologies are based on the formation of a shock wave mitigation barrier between the protection site and the explosion site. Contemporary protective systems use water mist as an extinguishing barrier. To achieve high effectiveness of the protective system, proper selection of water mist characteristics is important. The main factors defining shock wave attenuation in water mist include droplet size distribution, water concentration in the mist, droplet velocity and geometric properties of mist. This paper examines the process of attenuation of shock waves in mist with droplets ranging from 25 to 400 microns under different conditions of water mist location. Experiments were conducted at the Mining Institute with the use of a shock tube to study the processes of explosion suppression by a water mist barrier. The shock tube consists of a blast chamber, a tube, a system for the dosed supply of water, sensors, data recording equipment, and a process control module. Shock wave overpressure reduction coefficient was studied in the shock tube under two different locations of water mist: a) when water mist is created in direct contact with blast chamber and b) the blast chamber and the mist are separated by air space. It is established that in conditions when the air space distance between the blast chamber and the mist is 1 meter, overpressure reduction coefficient is 1.5-1.6 times higher than in conditions when water mist is created in direct contact with blast chamber.

Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor

DEFF Research Database (Denmark)

Kulahin, Nikolaj; Li, Shizhong; Hinsby, Anders Mørkeberg

2008-01-01

The neuronal cell adhesion molecule (CAM) L1 promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). The present study demonstrates a direct interaction between L1 fibronectin type III (FN3) modules I-V and FGFR1 immunoglobulin (Ig) modules II...

Proteasome activity or expression is not altered by activation of the heat shock transcription factor Hsf1 in cultured fibroblasts or myoblasts.

Science.gov (United States)

Taylor, David M; Kabashi, Edor; Agar, Jeffrey N; Minotti, Sandra; Durham, Heather D

2005-01-01

Heat shock proteins (Hsps) with chaperoning function work together with the ubiquitin-proteasome pathway to prevent the accumulation of misfolded, potentially toxic proteins, as well as to control catabolism of the bulk of cytoplasmic, cellular protein. There is evidence for the involvement of both systems in neurodegenerative disease, and a therapeutic target is the heat shock transcription factor, Hsf1, which mediates upregulation of Hsps in response to cellular stress. The mechanisms regulating expression of proteasomal proteins in mammalian cells are less well defined. To assess any direct effect of Hsf1 on expression of proteasomal subunits and activity in mammalian cells, a plasmid encoding a constitutively active form of Hsf1 (Hsf1act) was expressed in mouse embryonic fibroblasts lacking Hsf1 and in cultured human myoblasts. Plasmid encoding an inactivatible form of Hsf1 (Hsf1inact) served as control. In cultures transfected with plasmid hsf1act, robust expression of the major stress-inducible Hsp, Hsp70, occurred but not in cultures transfected with hsf1inact. No significant changes in the level of expression of representative proteasomal proteins (structural [20Salpha], a nonpeptidase beta subunit [20Sbeta3], or 2 regulatory subunits [19S subunit 6b, 11 Salpha]) or in chymotrypsin-, trypsin-, and caspaselike activities of the proteasome were measured. Thus, stress-induced or pharmacological activation of Hsf1 in mammalian cells would upregulate Hsps but not directly affect expression or activity of proteasomes.

Noradrenergic facilitation of shock-probe defensive burying in lateral septum of rats, and modulation by chronic treatment with desipramine.

Science.gov (United States)

Bondi, Corina O; Barrera, Gabriel; Lapiz, M Danet S; Bedard, Tania; Mahan, Amy; Morilak, David A

2007-03-30

We have previously shown that acute stress-induced release of norepinephrine (NE) facilitates anxiety-like behavioral responses to stress, such as reduction in open-arm exploration on the elevated-plus maze and in social behavior on the social interaction test. Since these responses represent inhibition of ongoing behavior, it is important to also address whether NE facilitates a response that represents an activation of behavior. Correspondingly, it is unknown how a chronic elevation in tonic steady-state noradrenergic (NA) neurotransmission induced by NE reuptake blockade might alter this acute modulatory function, a regulatory process that may be pertinent to the anxiolytic effects of NE reuptake blockers such as desipramine (DMI). Therefore, in this study, we investigated noradrenergic modulation of the shock-probe defensive burying response in the lateral septum (LS). In experiment 1, shock-probe exposure induced an acute 3-fold increase in NE levels measured in LS of male Sprague-Dawley rats by microdialysis. Shock-probe exposure also induced a modest rise in plasma ACTH, taken as an indicator of perceived stress, that returned to baseline more rapidly in rats that were allowed to bury the probe compared to rats prevented from burying by providing them with minimal bedding, indicating that the active defensive burying behavior is an effective coping strategy that reduces the impact of acute shock probe-induced stress. In experiment 2, blockade of either alpha(1)- or beta-adrenergic receptors in LS by local antagonist microinjection immediately before testing reduced defensive burying and increased immobility. In the next experiment, chronic DMI treatment increased basal extracellular NE levels in LS, and attenuated the acute shock probe-induced increase in NE release in LS relative to baseline. Chronic DMI treatment decreased shock-probe defensive burying behavior in a time-dependent manner, apparent only after 2 weeks or more of drug treatment. Moreover

Influence of selected factors on bovine spermatozoa cold shock resistance

Directory of Open Access Journals (Sweden)

Luděk Stádník

2015-01-01

Full Text Available The objectives of this study were to determine the effects of sire, extender, and addition of Low Density Lipoprotein (LDL to extenders used on the percentage rate of spermatozoa survival after cold shock. Two groups of extenders were compared: without LDL addition (control variants and LDL enriched (experimental variants. Three extenders were used: AndroMed®, Bioxcell®, and Triladyl®. Experimental variants included 4–8% LDL addition into the AndroMed® and Bioxcell® extenders, and 6–10% LDL addition into the Triladyl® extender. In total, 12 samples of fresh semen were collected from 4 bulls during a period of 8 weeks. Bovine spermatozoa cold shock resistance (1 ± 1 °C, 10 min was evaluated by the percentage rate of live sperm using eosin-nigrosine staining immediately and after heat incubation (37 ± 1 °C, 120 min. The results showed the effect of sire as important and individual differences between selected sires in their sperm resistance against cold shock were confirmed. AndroMed® and Bioxcell® were found to be providing better protection of bull semen to cold shock compared to Triladyl® due to lower decline of live sperm proportion. Our results detected a positive effect of LDL addition on sperm resistance against cold shock, especially on lower decrease of live sperm percentage rate after 120 min of the heat test (P < 0.05. Further studies are needed to assess the optimal concentration of LDL in various kinds of extenders as well to state ideal time and temperature conditions for ensuring LDL reaction with sperm.

Generation of high pressure shocks relevant to the shock-ignition intensity regime

Czech Academy of Sciences Publication Activity Database

Batani, D.; Antonelli, L.; Atzeni, S.; Badziak, J.; Baffigi, F.; Chodukowski, T.; Consoli, F.; Cristoforetti, G.; De Angelis, R.; Dudžák, Roman; Folpini, G.; Giuffrida, L.; Gizzi, L.A.; Kalinowska, Z.; Koester, P.; Krouský, Eduard; Krůs, Miroslav; Labate, L.; Levato, Tadzio; Maheut, Y.; Malka, G.; Margarone, Daniele; Marocchino, A.; Nejdl, Jaroslav; Nicolai, Ph.; O’Dell, T.; Pisarczyk, T.; Renner, Oldřich; Rhee, Y.-J.; Ribeyre, X.; Richetta, M.; Rosinski, M.; Sawicka, Magdalena; Schiavi, A.; Skála, Jiří; Šmíd, Michal; Spindloe, Ch.; Ullschmied, Jiří; Velyhan, Andriy; Vinci, T.

2014-01-01

Roč. 21, č. 3 (2014), 032710-032710 ISSN 1070-664X R&D Projects: GA MŠk(CZ) LC528; GA MŠk LM2010014 Institutional support: RVO:61389021 ; RVO:68378271 Keywords : High-pressure shocks * shock ignition * inertial confinement fusion * PALS laser Subject RIV: BL - Plasma and Gas Discharge Physics; BL - Plasma and Gas Discharge Physics (FZU-D) Impact factor: 2.142, year: 2014 http://dx.doi.org/10.1063/1.4869715

Numerical study of the Kadomtsev-Petviashvili equation and dispersive shock waves

Science.gov (United States)

Grava, T.; Klein, C.; Pitton, G.

2018-02-01

A detailed numerical study of the long time behaviour of dispersive shock waves in solutions to the Kadomtsev-Petviashvili (KP) I equation is presented. It is shown that modulated lump solutions emerge from the dispersive shock waves. For the description of dispersive shock waves, Whitham modulation equations for KP are obtained. It is shown that the modulation equations near the soliton line are hyperbolic for the KPII equation while they are elliptic for the KPI equation leading to a focusing effect and the formation of lumps. Such a behaviour is similar to the appearance of breathers for the focusing nonlinear Schrödinger equation in the semiclassical limit.

Shock compression of synthetic opal

International Nuclear Information System (INIS)

Inoue, A; Okuno, M; Okudera, H; Mashimo, T; Omurzak, E; Katayama, S; Koyano, M

2010-01-01

Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO 4 tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO 2 glass. However, internal silanole groups still remain even at 38.1 GPa.

Shock compression of synthetic opal

Science.gov (United States)

Inoue, A.; Okuno, M.; Okudera, H.; Mashimo, T.; Omurzak, E.; Katayama, S.; Koyano, M.

2010-03-01

Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO4 tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO2 glass. However, internal silanole groups still remain even at 38.1 GPa.

Shock compression of synthetic opal

Energy Technology Data Exchange (ETDEWEB)

Inoue, A; Okuno, M; Okudera, H [Department of Earth Sciences, Kanazawa University Kanazawa, Ishikawa, 920-1192 (Japan); Mashimo, T; Omurzak, E [Shock Wave and Condensed Matter Research Center, Kumamoto University, Kumamoto, 860-8555 (Japan); Katayama, S; Koyano, M, E-mail: okuno@kenroku.kanazawa-u.ac.j [JAIST, Nomi, Ishikawa, 923-1297 (Japan)

2010-03-01

Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO{sub 4} tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO{sub 2} glass. However, internal silanole groups still remain even at 38.1 GPa.

Prospects of engineering thermotolerance in crops through modulation of heat stress transcription factor and heat shock protein networks.

Science.gov (United States)

Fragkostefanakis, Sotirios; Röth, Sascha; Schleiff, Enrico; Scharf, Klaus-Dieter

2015-09-01

Cell survival under high temperature conditions involves the activation of heat stress response (HSR), which in principle is highly conserved among different organisms, but shows remarkable complexity and unique features in plant systems. The transcriptional reprogramming at higher temperatures is controlled by the activity of the heat stress transcription factors (Hsfs). Hsfs allow the transcriptional activation of HSR genes, among which heat shock proteins (Hsps) are best characterized. Hsps belong to multigene families encoding for molecular chaperones involved in various processes including maintenance of protein homeostasis as a requisite for optimal development and survival under stress conditions. Hsfs form complex networks to activate downstream responses, but are concomitantly subjected to cell-type-dependent feedback regulation through factor-specific physical and functional interactions with chaperones belonging to Hsp90, Hsp70 and small Hsp families. There is increasing evidence that the originally assumed specialized function of Hsf/chaperone networks in the HSR turns out to be a complex central stress response system that is involved in the regulation of a broad variety of other stress responses and may also have substantial impact on various developmental processes. Understanding in detail the function of such regulatory networks is prerequisite for sustained improvement of thermotolerance in important agricultural crops. © 2014 John Wiley & Sons Ltd.

Radiation-mediated Shocks in Gamma-Ray Bursts: Pair Creation

Science.gov (United States)

Lundman, Christoffer; Beloborodov, Andrei M.; Vurm, Indrek

2018-05-01

Relativistic sub-photospheric shocks are a possible mechanism for producing prompt gamma-ray burst (GRB) emission. Such shocks are mediated by scattering of radiation. We introduce a time-dependent, special relativistic code which dynamically couples Monte Carlo radiative transfer to the flow hydrodynamics. The code also self-consistently follows electron–positron pair production in photon–photon collisions. We use the code to simulate shocks with properties relevant to GRBs. We focus on plane-parallel solutions, which are accurate deep below the photosphere. The shock generates a power-law photon spectrum through the first-order Fermi mechanism, extending upward from the typical upstream photon energy. Strong (high Mach number) shocks produce rising νF ν spectra. We observe that in non-relativistic shocks the spectrum extends to {E}\\max ∼ {m}e{v}2, where v is the speed difference between the upstream and downstream. In relativistic shocks the spectrum extends to energies E> 0.1 {m}e{c}2 where its slope softens due to Klein–Nishina effects. Shocks with Lorentz factors γ > 1.5 are prolific producers of electron–positron pairs, yielding hundreds of pairs per proton. The main effect of pairs is to reduce the shock width by a factor of ∼ {Z}+/- -1. Most pairs annihilate far downstream of the shock, and the radiation spectrum relaxes to a Wien distribution, reaching equilibrium with the plasma at a temperature determined by the shock jump conditions and the photon number per proton. We discuss the implications of our results for observations of radiation generated by sub-photospheric shocks.

Theoretical Research on Thermal Shock Resistance of Ultra-High Temperature Ceramics Focusing on the Adjustment of Stress Reduction Factor

Directory of Open Access Journals (Sweden)

Daining Fang

2013-02-01

Full Text Available The thermal shock resistance of ceramics depends on not only the mechanical and thermal properties of materials, but also the external constraint and thermal condition. So, in order to study the actual situation in its service process, a temperature-dependent thermal shock resistance model for ultra-high temperature ceramics considering the effects of the thermal environment and external constraint was established based on the existing theory. The present work mainly focused on the adjustment of the stress reduction factor according to different thermal shock situations. The influences of external constraint on both critical rupture temperature difference and the second thermal shock resistance parameter in either case of rapid heating or cooling conditions had been studied based on this model. The results show the necessity of adjustment of the stress reduction factor in different thermal shock situations and the limitations of the applicable range of the second thermal shock resistance parameter. Furthermore, the model was validated by the finite element method.

Voyager 1 in the foreshock, termination shock, and heliosheath.

Science.gov (United States)

Decker, R B; Krimigis, S M; Roelof, E C; Hill, M E; Armstrong, T P; Gloeckler, G; Hamilton, D C; Lanzerotti, L J

2005-09-23

Voyager 1 (V1) began measuring precursor energetic ions and electrons from the heliospheric termination shock (TS) in July 2002. During the ensuing 2.5 years, average particle intensities rose as V1 penetrated deeper into the energetic particle foreshock of the TS. Throughout 2004, V1 observed even larger, fluctuating intensities of ions from 40 kiloelectron volts (keV) to >/=50 megaelectron volts per nucleon and of electrons from >26 keV to >/=350 keV. On day 350 of 2004 (2004/350), V1 observed an intensity spike of ions and electrons that was followed by a sustained factor of 10 increase at the lowest energies and lesser increases at higher energies, larger than any intensities since V1 was at 15 astronomical units in 1982. The estimated solar wind radial flow speed was positive (outward) at approximately +100 kilometers per second (km s(-1)) from 2004/352 until 2005/018, when the radial flows became predominantly negative (sunward) and fluctuated between approximately -50 and 0 km s(-1) until about 2005/110; they then became more positive, with recent values (2005/179) of approximately +50 km s(-1). The energetic proton spectrum averaged over the postshock period is apparently dominated by strongly heated interstellar pickup ions. We interpret these observations as evidence that V1 was crossed by the TS on 2004/351 (during a tracking gap) at 94.0 astronomical units, evidently as the shock was moving radially inward in response to decreasing solar wind ram pressure, and that V1 has remained in the heliosheath until at least mid-2005.

Modulation of transcription factors by curcumin.

Science.gov (United States)

Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

2007-01-01

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

Multi-shocks generation and collapsing instabilities induced by competing nonlinearities

KAUST Repository

Crosta, Matteo; Trillo, Stefano; Fratalocchi, Andrea

2012-01-01

We investigate dispersive shock dynamics in materials with competing cubic-quintic nonlinearities. Whitham theory of modulation, hydrodynamic analysis and numerics demonstrate a rich physical scenario, ranging from multi-shock generation to collapse.

Mapping temperature-induced conformational changes in the Escherichia coli heat shock transcription factor sigma 32 by amide hydrogen exchange

DEFF Research Database (Denmark)

Rist, Wolfgang; Jørgensen, Thomas J D; Roepstorff, Peter

2003-01-01

Stress conditions such as heat shock alter the transcriptional profile in all organisms. In Escherichia coli the heat shock transcription factor, sigma 32, out-competes upon temperature up-shift the housekeeping sigma-factor, sigma 70, for binding to core RNA polymerase and initiates heat shock...... gene transcription. To investigate possible heat-induced conformational changes in sigma 32 we performed amide hydrogen (H/D) exchange experiments under optimal growth and heat shock conditions combined with mass spectrometry. We found a rapid exchange of around 220 of the 294 amide hydrogens at 37...... degrees C, indicating that sigma 32 adopts a highly flexible structure. At 42 degrees C we observed a slow correlated exchange of 30 additional amide hydrogens and localized it to a helix-loop-helix motif within domain sigma 2 that is responsible for the recognition of the -10 region in heat shock...

Cosmic Rays Accelerated at Cosmological Shock Waves Renyi Ma1 ...

Indian Academy of Sciences (India)

Cosmic Rays Accelerated at Cosmological Shock Waves. Renyi Ma1,2,∗ ... ratio of CR to thermal energy in the ICM and WHIM based on numerical simulations and diffusive shock ... Hence, the nonthermal radiation of CRs may provide us a.

On possible structures of transverse ionizing shock waves

International Nuclear Information System (INIS)

Liberman, M.A.; Velikovich, A.L.

1978-01-01

The possible structures of ionizing shock waves propagating in gases across the magnetic field are investigated taking account of both ionization kinetics and the non-isothermality of the plasma which is formed within the shock front. It is shown that a definite factor in shaping the structure of the transverse ionizing shock wave is photo-ionization of the neutral gas across the front. The paper includes a study of the evolution of the transverse ionizing shock front with regard to photo-ionization, disclosing that a stable stationary shock structure emerges only in boundary conditions which are close to magnetohydrodynamic ones, i.e. upsilon 1 H 1 = upsilon 2 H 2 . In the case of strong transverse ionizing shock waves, when the flux of ionizing radiation across the front is great, the shock structure is obviously magnetohydrodynamic. (author)

Effects of response-shock interval and shock intensity on free-operant avoidance responding in the pigeon1

Science.gov (United States)

Klein, Marty; Rilling, Mark

1972-01-01

Two experiments investigated free-operant avoidance responding with pigeons using a treadle-pressing response. In Experiment I, pigeons were initially trained on a free-operant avoidance schedule with a response-shock interval of 32 sec and a shock-shock interval of 10 sec, and were subsequently exposed to 10 values of the response-shock parameter ranging from 2.5 to 150 sec. The functions relating response rate to response-shock interval were similar to the ones reported by Sidman in his 1953 studies employing rats, and were independent of the order of presentation of the response-shock values. Shock rates decreased as response-shock duration increased. In Experiment II, a free-operant avoidance schedule with a response-shock interval of 20 sec and a shock-shock interval of 5 sec was used, and shock intensities were varied over five values ranging from 2 to 32 mA. Response rates increased markedly as shock intensity increased from 2 to 8 mA, but rates changed little with further increases in shock intensity. Shock rates decreased as intensity increased from 2 to 8 mA, and showed little change as intensity increased from 8 to 32 mA. PMID:4652617

IL-1B rs16944 polymorphism is related to septic shock and death.

Science.gov (United States)

Jiménez-Sousa, María Ángeles; Medrano, Luz M; Liu, Pilar; Almansa, Raquel; Fernández-Rodríguez, Amanda; Gómez-Sánchez, Esther; Rico, Lucía; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Resino, Salvador

2017-01-01

IL-1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL-1B rs16944 polymorphism is associated with the onset of septic shock and death after major surgery. We performed a case-control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL-1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC). The frequency of septic shock was higher in patients with IL-1B rs16944 AA genotype than in patients with IL-1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL-1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population [adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042], but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL-1B rs16944 AA genotype was also associated with higher likelihood of septic shock-related death in all population [aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035]. IL-1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

RhoA Activation Sensitizes Cells to Proteotoxic Stimuli by Abrogating the HSF1-Dependent Heat Shock Response.

Directory of Open Access Journals (Sweden)

Roelien A M Meijering

Full Text Available The heat shock response (HSR is an ancient and highly conserved program of stress-induced gene expression, aimed at reestablishing protein homeostasis to preserve cellular fitness. Cells that fail to activate or maintain this protective response are hypersensitive to proteotoxic stress. The HSR is mediated by the heat shock transcription factor 1 (HSF1, which binds to conserved heat shock elements (HSE in the promoter region of heat shock genes, resulting in the expression of heat shock proteins (HSP. Recently, we observed that hyperactivation of RhoA conditions cardiomyocytes for the cardiac arrhythmia atrial fibrillation. Also, the HSR is annihilated in atrial fibrillation, and induction of HSR mitigates sensitization of cells to this disease. Therefore, we hypothesized active RhoA to suppress the HSR resulting in sensitization of cells for proteotoxic stimuli.Stimulation of RhoA activity significantly suppressed the proteotoxic stress-induced HSR in HL-1 atrial cardiomyocytes as determined with a luciferase reporter construct driven by the HSF1 regulated human HSP70 (HSPA1A promoter and HSP protein expression by Western Blot analysis. Inversely, RhoA inhibition boosted the proteotoxic stress-induced HSR. While active RhoA did not preclude HSF1 nuclear accumulation, phosphorylation, acetylation, or sumoylation, it did impair binding of HSF1 to the hsp genes promoter element HSE. Impaired binding results in suppression of HSP expression and sensitized cells to proteotoxic stress.These results reveal that active RhoA negatively regulates the HSR via attenuation of the HSF1-HSE binding and thus may play a role in sensitizing cells to proteotoxic stimuli.

Strong shock wave and areal mass oscillations associated with impulsive loading of planar laser targets

International Nuclear Information System (INIS)

Velikovich, A.L.; Schmitt, A.J.; Metzler, N.; Gardner, J.H.

2003-01-01

When a rippled surface of a planar target is irradiated with a short (subnanosecond) laser pulse, the shock wave launched into the target and the mass distribution of the shocked plasma will oscillate. These oscillations are found to be surprisingly strong compared, for example, to the case when the laser radiation is not turned off but rather keeps pushing the shock wave into the target. Being stronger than the areal mass oscillations due to ablative Richtmyer-Meshkov instability and feedout in planar targets, which have recently been observed at the Naval Research Laboratory (NRL) [Aglitskiy et al., Phys. Plasmas 9, 2264 (2002)], these oscillations should therefore be directly observable with the same diagnostic technique. Irradiation of a target with a short laser pulse represents a particular case of an impulsive loading, a fast release of finite energy in a thin layer near the surface of a target. Renewed interest to the impulsive loading in the area of direct-drive laser fusion is due to the recent proposals of using a short pulse prior to the drive pulse to make the target more resistant to laser imprint and Rayleigh-Taylor growth. Impulsive loading produces a shock wave that propagates into the target and is immediately followed by an expansion wave, which gradually reduces the shock strength. If the irradiated surface is rippled, then, while the shock wave propagates through the target, its modulation amplitude grows, exceeding the initial ripple amplitude by a factor of 2 or more. The oscillating areal mass reaches the peak values that exceed the initial mass modulation amplitude (density times ripple height) by a factor of 5-7 or more, and reverses its phase several times after the laser pulse is over. The oscillatory growth is more pronounced in fluids with higher shock compressibility and is probably related to the Vishniac's instability of a blast wave. Frequency of the oscillations is determined by the speed of sound in the shocked material, and

Extrapolating the Trends of Test Drop Data with Opening Shock Factor Calculations: the Case of the Orion Main and Drogue Parachutes Inflating to 1st Reefed Stage

Science.gov (United States)

Potvin, Jean; Ray, Eric

2017-01-01

We describe a new calculation of the opening shock factor C (sub k) characterizing the inflation performance of NASA's Orion spacecraft main and drogue parachutes opening under a reefing constraint (1st stage reefing), as currently tested in the Capsule Parachute Assembly System (CPAS) program. This calculation is based on an application of the Momentum-Impulse Theorem at low mass ratio (R (sub m) is less than 10 (sup -1)) and on an earlier analysis of the opening performance of drogues decelerating point masses and inflating along horizontal trajectories. Herein we extend the reach of the Theorem to include the effects of payload drag and gravitational impulse during near-vertical motion - both important pre-requisites for CPAS parachute analysis. The result is a family of C (sub k) versus R (sub m) curves which can be used for extrapolating beyond the drop-tested envelope. The paper proves this claim in the case of the CPAS Mains and Drogues opening while trailing either a Parachute Compartment Drop Test Vehicle or a Parachute Test Vehicle (an Orion capsule boiler plate). It is seen that in all cases the values of the opening shock factor can be extrapolated over a range in mass ratio that is at least twice that of the test drop data.

Constraining Relativistic Bow Shock Properties in Rotation-powered Millisecond Pulsar Binaries

Energy Technology Data Exchange (ETDEWEB)

Wadiasingh, Zorawar; Venter, Christo; Böttcher, Markus [Centre for Space Research, North–West University, Potchefstroom (South Africa); Harding, Alice K. [Astrophysics Science Division, NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Baring, Matthew G., E-mail: zwadiasingh@gmail.com [Department of Physics and Astronomy, Rice University, Houston, TX 77251 (United States)

2017-04-20

Multiwavelength follow-up of unidentified Fermi sources has vastly expanded the number of known galactic-field “black widow” and “redback” millisecond pulsar binaries. Focusing on their rotation-powered state, we interpret the radio to X-ray phenomenology in a consistent framework. We advocate the existence of two distinct modes differing in their intrabinary shock orientation, distinguished by the phase centering of the double-peaked X-ray orbital modulation originating from mildly relativistic Doppler boosting. By constructing a geometric model for radio eclipses, we constrain the shock geometry as functions of binary inclination and shock standoff R {sub 0}. We develop synthetic X-ray synchrotron orbital light curves and explore the model parameter space allowed by radio eclipse constraints applied on archetypal systems B1957+20 and J1023+0038. For B1957+20, from radio eclipses the standoff is R {sub 0} ∼ 0.15–0.3 fraction of binary separation from the companion center, depending on the orbit inclination. Constructed X-ray light curves for B1957+20 using these values are qualitatively consistent with those observed, and we find occultation of the shock by the companion as a minor influence, demanding significant Doppler factors to yield double peaks. For J1023+0038, radio eclipses imply R {sub 0} ≲ 0.4, while X-ray light curves suggest 0.1 ≲ R {sub 0} ≲ 0.3 (from the pulsar). Degeneracies in the model parameter space encourage further development to include transport considerations. Generically, the spatial variation along the shock of the underlying electron power-law index should yield energy dependence in the shape of light curves, motivating future X-ray phase-resolved spectroscopic studies to probe the unknown physics of pulsar winds and relativistic shock acceleration therein.

Constraining Relativistic Bow Shock Properties in Rotation-Powered Millisecond Pulsar Binaries

Science.gov (United States)

Wadiasingh, Zorawar; Harding, Alice K.; Venter, Christo; Bottcher, Markus; Baring, Matthew G.

2017-01-01

Multiwavelength follow-up of unidentified Fermi sources has vastly expanded the number of known galactic-field "black widow" and "redback" millisecond pulsar binaries. Focusing on their rotation-powered state, we interpret the radio to X-ray phenomenology in a consistent framework. We advocate the existence of two distinct modes differing in their intrabinary shock orientation, distinguished by the phase-centering of the double-peaked X-ray orbital modulation originating from mildly-relativistic Doppler boosting. By constructing a geometric model for radio eclipses, we constrain the shock geometry as functions of binary inclination and shock stand-off R(sub 0). We develop synthetic X-ray synchrotron orbital light curves and explore the model parameter space allowed by radio eclipse constraints applied on archetypal systems B1957+20 and J1023+0038. For B1957+20, from radio eclipses the stand-off is R(sub 0) approximately 0:15 - 0:3 fraction of binary separation from the companion center, depending on the orbit inclination. Constructed X-ray light curves for B1957+20 using these values are qualitatively consistent with those observed, and we find occultation of the shock by the companion as a minor influence, demanding significant Doppler factors to yield double peaks. For J1023+0038, radio eclipses imply R(sub 0) is approximately less than 0:4 while X-ray light curves suggest 0:1 is approximately less than R(sub 0) is approximately less than 0:3 (from the pulsar). Degeneracies in the model parameter space encourage further development to include transport considerations. Generically, the spatial variation along the shock of the underlying electron power-law index should yield energy-dependence in the shape of light curves motivating future X-ray phase-resolved spectroscopic studies to probe the unknown physics of pulsar winds and relativistic shock acceleration therein.

CONSTRAINING RELATIVISTIC BOW SHOCK PROPERTIES IN ROTATION-POWERED MILLISECOND PULSAR BINARIES

Science.gov (United States)

Wadiasingh, Zorawar; Harding, Alice K.; Venter, Christo; Böttcher, Markus; Baring, Matthew G.

2018-01-01

Multiwavelength followup of unidentified Fermi sources has vastly expanded the number of known galactic-field “black widow” and “redback” millisecond pulsar binaries. Focusing on their rotation-powered state, we interpret the radio to X-ray phenomenology in a consistent framework. We advocate the existence of two distinct modes differing in their intrabinary shock orientation, distinguished by the phase-centering of the double-peaked X-ray orbital modulation originating from mildly-relativistic Doppler boosting. By constructing a geometric model for radio eclipses, we constrain the shock geometry as functions of binary inclination and shock stand-off R0. We develop synthetic X-ray synchrotron orbital light curves and explore the model parameter space allowed by radio eclipse constraints applied on archetypal systems B1957+20 and J1023+0038. For B1957+20, from radio eclipses the stand-off is R0 ~ 0.15–0.3 fraction of binary separation from the companion center, depending on the orbit inclination. Constructed X-ray light curves for B1957+20 using these values are qualitatively consistent with those observed, and we find occultation of the shock by the companion as a minor influence, demanding significant Doppler factors to yield double peaks. For J1023+0038, radio eclipses imply R0 ≲ 0.4 while X-ray light curves suggest 0.1 ≲ R0 ≲ 0.3 (from the pulsar). Degeneracies in the model parameter space encourage further development to include transport considerations. Generically, the spatial variation along the shock of the underlying electron power-law index should yield energy-dependence in the shape of light curves motivating future X-ray phase-resolved spectroscopic studies to probe the unknown physics of pulsar winds and relativistic shock acceleration therein. PMID:29651167

Shock in the emergency department

DEFF Research Database (Denmark)

Holler, Jon Gitz; Henriksen, Daniel Pilsgaard; Mikkelsen, Søren

2016-01-01

BACKGROUND: The knowledge of the frequency and associated mortality of shock in the emergency department (ED) is limited. The aim of this study was to describe the incidence, all-cause mortality and factors associated with death among patients suffering shock in the ED. METHODS: Population...... failures. Outcomes were annual incidence per 100,000 person-years at risk (pyar), all-cause mortality at 0-7, and 8-90 days and risk factors associated with death. RESULTS: We identified 1646 of 438,191 (0.4 %) ED patients with shock at arrival. Incidence of shock increased from 53.8 to 80.6 cases per 100...

Thermoluminescence of annealed and shock-loaded feldspar

International Nuclear Information System (INIS)

Hartmetz, C.P.

1988-01-01

Samples of oligoclase and bytownite were shock-loaded to a variety of pressures, and annealed for a variety of temperatures and times. The effect of Mrad doses of gamma-rays on oligoclase TL were also studied. After these treatments, thermoluminescence (TL) and X-ray diffraction (XRD) measurements were made to: (1) determine the effects of shock on terrestrial feldspar and compare with variations in the TL emission of ordinary chondrites (OCs); (2) determine if disordering in feldspar was responsible for any related changes in TL properties of OCs; (3) determine if the combined effect of shock plus annealing causes the changes in TL properties; (4) see if radiation damage from cosmic ray exposure plays a role in the TL variations; (5) examine the implications of this work to the thermal and shock histories of OCs. The lightly shock-loaded and annealed oligoclase samples have a dominant peak temperature of 120-140 C, identical to type 3.3-3.5 OCs. The heavily shocked samples dominant peak is at 230C, similar to type > 3.5 OCs . While the heavily annealed/disordered oligoclase samples have a peak at 280C, this peak is rarely observed in OCs. Radiation damage from Mrad doses of gamma-rays produced no change in peak temperature, but facilitated the shift to higher peak temperatures. The TL sensitivity of the shocked samples decreased by a factor of 25. Samples annealed at low temperatures (438-533C) showed a factor of 2 decrease in TL, but at the highest temperatures, the TL was a factor of 8 higher

Is shock index associated with outcome in children with sepsis/septic shock?*.

Science.gov (United States)

Yasaka, Yuki; Khemani, Robinder G; Markovitz, Barry P

2013-10-01

To investigate the association between PICU shock index (the ratio of heart rate to systolic blood pressure) and PICU mortality in children with sepsis/septic shock. To explore cutoff values for shock index for ICU mortality, how change in shock index over the first 6 hours of ICU admission is associated with outcome, and how the use of vasoactive therapy may affect shock index and its association with outcome. Retrospective cohort. Single-center tertiary PICU. Five hundred forty-four children with the diagnosis of sepsis/septic shock. None. From January 2003 to December 2009, 544 children met International Pediatric Sepsis Consensus Conference of 2005 criteria for sepsis/septic shock. Overall mortality was 23.7%. Among all patients, hourly shock index was associated with mortality: odds ratio of ICU mortality at 0 hour, 1.08, 95% CI (1.04-1.12); odds ratio at 1 hour, 1.09 (1.04-1.13); odds ratio at 2 hours, 1.09 (1.05-1.13); and odds ratio at 6 hours, 1.11 (1.06-1.15). When stratified by age, early shock index was associated with mortality only in children 1-3 and more than or equal to 12 years old. Area under the receiver operating characteristic curve in age 1-3 and more than or equal to 12 years old for shock index at admission was 0.69 (95% CI, 0.58-0.80) and 0.62 (95% CI, 0.52-0.72) respectively, indicating a fair predictive marker. Although higher shock index was associated with increased risk of mortality, there was no particular cutoff value with adequate positive or negative likelihood ratios to identify mortality in any age group of children. The improvement of shock index in the first 6 hours of ICU admission was not associated with outcome when analyzed in all patients. However, among patients whose shock index were above the 50th percentile at ICU admission for each age group, improvement of shock index was associated with lower ICU mortality in children between 1-3 and more than or equal to 12 years old (p = 0.02 and p = 0.03, respectively). When

Structure of oblique subcritical bow shocks: ISEE 1 and 2 observations

International Nuclear Information System (INIS)

Mellott, M.M.; Greenstadt, E.W.

1984-01-01

We have studied the structural elements, including shock ramps and precursor wave trains, of a series of oblique low-Mach number terrestrial bow shocks. We used magnetic field data from the dual ISEE 1 and 2 spacecraft to determine the scale lengths of various elements of shock structure as well as wavelengths and wave polarizations. Bow shocks structure under these conditions is esstentially that of a large-amplitude damped whistler mode wave which extends upstream in the form of a precursor wave train. Shock thicknesses, which are determined by the dispersive properties of the ambient plasma, are too broad to support current-driven electrostatic waves, ruling out such turbulence as the source of dissipation in these shocks. Dissipative processes are reflected in the damping of the precursors, and dissipative scale lengths are approx.200--800 km (several times greater than shock thicknesses). Precursor damping is not related to shock normal angle or Mach number, but is correlated with T/sub e//T/sub t/. The source of the dissipation in the shocks does not appear to be wave-wave decay of the whistlers, for which no evidence is found. We cannot rule out the possibility of contribution to the dissipation from ion acoustic and, or lower hybrid mode turbulence, but interaction of the whistler itself with upstream electrons offers a simpler and more self-consistent explanation for the observed wave train damping

Predicting optimal back-shock times in ultrafiltration hollow fibre modules through path-lines

DEFF Research Database (Denmark)

Vinther, Frank; Pinelo, Manuel; Brøns, Morten

2014-01-01

This paper presents a two dimensional mathematical model of back-shocking in ultrafiltration. The model investigates the effect of back-shocking on concentration polarization. The model shows a positive effect on both the volumetric flux and the observed rejection when back-shocking is applied as...

Slow shocks and their transition to fast shocks in the inner solar wind

International Nuclear Information System (INIS)

Wang, Y.C.

1987-01-01

The jump conditions of MHD shocks may be directly calculated as functions of three upstream conditions: the shock Alfven number based on the normal component of the relative shock speed, the shock angle, and the plasma β value. The shock Alfven number is less than 1 for a slow shock and greater than 1 for a fast shock. A traveling, forward shock can be a slow shock in coronal space, where the Alfven speed is of the order of 1000 km/s. The surface of a forward slow shock has a bow-shaped geometry with its nose facing toward the sun. The decrease in the Alfven speed at increasing heliocentric distance causes the shock Alfven number of a forward slow shock to become greater than 1, and the shock eventually evolves from a slow shock into a fast shock. During the transition the shock system consists of a slow shock, a fast shock, and a rotational discontinuity. They intersect along a closed transition line. As the system moves outward from the sun, the area enclosed by the transition line expands, the fast shock grows stronger, and the slow shock becomes weaker. Eventually, the slow shock diminishes, and the entire shock system evolves into a forward fast shock. copyrightAmerican Geophysical Union 1987

High-accuracy self-calibration method for dual-axis rotation-modulating RLG-INS

Science.gov (United States)

Wei, Guo; Gao, Chunfeng; Wang, Qi; Wang, Qun; Long, Xingwu

2017-05-01

Inertial navigation system has been the core component of both military and civil navigation systems. Dual-axis rotation modulation can completely eliminate the inertial elements constant errors of the three axes to improve the system accuracy. But the error caused by the misalignment angles and the scale factor error cannot be eliminated through dual-axis rotation modulation. And discrete calibration method cannot fulfill requirements of high-accurate calibration of the mechanically dithered ring laser gyroscope navigation system with shock absorbers. This paper has analyzed the effect of calibration error during one modulated period and presented a new systematic self-calibration method for dual-axis rotation-modulating RLG-INS. Procedure for self-calibration of dual-axis rotation-modulating RLG-INS has been designed. The results of self-calibration simulation experiment proved that: this scheme can estimate all the errors in the calibration error model, the calibration precision of the inertial sensors scale factor error is less than 1ppm and the misalignment is less than 5″. These results have validated the systematic self-calibration method and proved its importance for accuracy improvement of dual -axis rotation inertial navigation system with mechanically dithered ring laser gyroscope.

Experimental Shock Transformation of Gypsum to Anhydrite: A New Low Pressure Regime Shock Indicator

Science.gov (United States)

Bell, Mary S.; Zolensky, Michael E.

2011-01-01

The shock behavior of gypsum is important in understanding the Cretaceous/Paleogene event and other terrestrial impacts that contain evaporite sediments in their targets (e.g., Mars Exploration Rover Spirit detected sulfate at Gusev crater, [1]). Most interest focuses on issues of devolatilization to quantify the production of SO2 to better understand its role in generating a temporary atmosphere and its effects on climate and biota [2,3]. Kondo and Ahrens [4] measured induced radiation emitted from single crystal gypsum shocked to 30 and 40 GPa. They observed greybody emission spectra corresponding to temperatures in the range of 3,000 to 4,000 K that are a factor of 2 to 10 times greater than calculated pressure-density energy equation of state temperatures (Hugoniot) and are high enough to melt gypsum. Chen et al. [5] reported results of shock experiments on anhydrite, gypsum, and mixtures of these phases with silica. Their observations indicated little or no devolatilization of anhydrite shocked to 42 GPa and that the fraction of sulfur, by mass, that degassed is approx.10(exp -2) of theoretical prediction. In another report of shock experiments on calcite, anhydrite, and gypsum, Badjukov et al. [6] observed only intensive plastic deformation in anhydrite shock loaded at 63 GPa, and gypsum converted to anhydrite when shock loaded at 56 GPa but have not experimentally shocked gypsum in a step-wise manner to constrain possible incipient transformation effects. Schmitt and Hornemann [7] shock loaded anhydrite and quartz to a peak pressure of 60 GPa and report the platy anhydrite grains were completely pseudomorphed by small crystallized anhydrite grains. However, no evidence of interaction between the two phases could be observed and they suggested that recrystallization of anhydrite grains is the result of a solid-state transformation. They concluded that significant decomposition of anhydrite requires shock pressures higher than 60 GPa. Gupta et al. [8

Iron oxide nanoparticles modulate heat shock proteins and organ specific markers expression in mice male accessory organs

Energy Technology Data Exchange (ETDEWEB)

Sundarraj, Kiruthika; Raghunath, Azhwar; Panneerselvam, Lakshmikanthan; Perumal, Ekambaram, E-mail: ekas2009@buc.edu.in

2017-02-15

With increased industrial utilization of iron oxide nanoparticles (Fe{sub 2}O{sub 3}-NPs), concerns on adverse reproductive health effects following exposure have been immensely raised. In the present study, the effects of Fe{sub 2}O{sub 3}-NPs exposure in the seminal vesicle and prostate gland were studied in mice. Mice were exposed to two different doses (25 and 50 mg/kg) of Fe{sub 2}O{sub 3}-NPs along with the control and analyzed the expressions of heat shock proteins (HSP60, HSP70 and HSP90) and organ specific markers (Caltrin, PSP94, and SSLP1). Fe{sub 2}O{sub 3}-NPs decreased food consumption, water intake, and organo-somatic index in mice with elevated iron levels in serum, urine, fecal matter, seminal vesicle and prostate gland. FTIR spectra revealed alterations in the functional groups of biomolecules on Fe{sub 2}O{sub 3}-NPs treatment. These changes are accompanied by increased lactate dehydrogenase levels with decreased total protein and fructose levels. The investigation of oxidative stress biomarkers demonstrated a significant increase in reactive oxygen species, nitric oxide, lipid peroxidation, protein carbonyl content and glutathione peroxidase with a concomitant decrement in the glutathione and ascorbic acid in the male accessory organs which confirmed the induction of oxidative stress. An increase in NADPH-oxidase-4 with a decrease in glutathione-S-transferase was observed in the seminal vesicle and prostate gland of the treated groups. An alteration in HSP60, HSP70, HSP90, Caltrin, PSP94, and SSLP1 expression was also observed. Moreover, accumulation of Fe{sub 2}O{sub 3}-NPs brought pathological changes in the seminal vesicle and prostate gland of treated mice. These findings provide evidence that Fe{sub 2}O{sub 3}-NPs could be an environmental risk factor for reproductive disease. - Highlights: • Fe{sub 2}O{sub 3}-NPs caused adverse effects on the seminal vesicle and prostate gland of mice • Heat shock proteins (Hsp60, 70 and 90) were

Arctigenin from Fructus Arctii is a novel suppressor of heat shock response in mammalian cells

Science.gov (United States)

Ishihara, Keiichi; Yamagishi, Nobuyuki; Saito, Youhei; Takasaki, Midori; Konoshima, Takao; Hatayama, Takumi

2006-01-01

Because heat shock proteins (Hsps) are involved in protecting cells and in the pathophysiology of diseases such as inflammation, cancer, and neurodegenerative disorders, the use of regulators of the expression of Hsps in mammalian cells seems to be useful as a potential therapeutic modality. To identify compounds that modulate the response to heat shock, we analyzed several natural products using a mammalian cell line containing an hsp promoter-regulated reporter gene. In this study, we found that an extract from Fructus Arctii markedly suppressed the expression of Hsp induced by heat shock. A component of the extract arctigenin, but not the component arctiin, suppressed the response at the level of the activation of heat shock transcription factor, the induction of mRNA, and the synthesis and accumulation of Hsp. Furthermore, arctigenin inhibited the acquisition of thermotolerance in mammalian cells, including cancer cells. Thus, arctigenin seemed to be a new suppressive regulator of heat shock response in mammalian cells, and may be useful for hyperthermia cancer therapy. PMID:16817321

Shock absorbency of factors in the shoe/heel interaction--with special focus on role of the heel pad.

Science.gov (United States)

Jørgensen, U; Bojsen-Møller, F

1989-06-01

The heel pad acts as a shock absorber in walking and in heel-strike running. In some patients, a reduction of its shock-absorbing capacity has been connected to the development of overuse injuries. In this article, the shock absorption of the heel pad as well as external shock absorbers are studied. Individual variation and the effect of trauma and confinement on the heel pad were specifically investigated. Drop tests, imitating heel impacts, were performed on a force plate. The test specimens were cadaver heel pads (n = 10); the shoe sole component consisted of ethyl vinyl acetate (EVA) foam and Sorbothane inserts. The shock absorption was significantly greater in the heel pad than in the external shock absorbers. The mean heel pad shock absorption was 1.1 times for EVA foam and 2.1 times for Sorbothane. The shock absorption varied by as much as 100% between heel pads. Trauma caused a decrease in the heel pad shock absorbency (24%), whereas heel pad confinement increased the shock absorbency (49% in traumatized heel pads and 29.5% in nontraumatized heel pads). These findings provide a biomechanical rationale for the clinical observations of a correlation between heel pad shock absorbency loss and heel strike-dependent overuse injuries. To increase shock absorbency, confinement of the heel pad should be attempted in vivo.

pH modulates the binding of early growth response protein 1 transcription factor to DNA.

Science.gov (United States)

Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

2013-08-01

The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

Particle acceleration at quasi-perpendicular shock waves: Theory and observations at 1 AU

International Nuclear Information System (INIS)

Parker, L. Neergaard; Zank, G. P.; Hu, Q.

2014-01-01

The injection of particles into the diffusive shock acceleration mechanism at highly perpendicular (where θ Bn > 70°) interplanetary shocks is investigated. This extends the previous study of Neergaard Parker and Zank which focused on the injection problem at quasi-parallel interplanetary shocks. We use observations at 1 AU to construct upstream Maxwellian and κ-distributions that are then diffusively accelerated by the shock, thus yielding the downstream accelerated particle distribution. We compare the theoretical accelerated particle distribution to observations at 1 AU using Advanced Composition Explorer data. We classify our results for quasi-perpendicular shocks into three subcategories: those with ratios of the theoretical spectral index to observed power law of >1, ∼ 1, and <1, and compare the magnetic power spectral density plots of these categories. We find that in general the assumed upstream particle distribution that best fits the energetic particle observations is best represented by a κ-distribution, with κ = 4. The magnetic field fluctuations were representative of quasi-perpendicular shocks and showed no particular bias toward our spectral ratio subcategories. The subcategory with spectral ratio <0.9 yielded the largest injection energies for all groups. In all but two of the cases in this study, there were enough particles in the solar wind thermal core to account for the accelerated distribution, thereby giving a lower limit to the required injection energy needed to diffusively accelerate particles at a quasi-perpendicular interplanetary shock. In the remaining two cases, an additional population of particles was required to match the appropriate amplitude of the spectral index. For these cases, we used a low energy (1-50 keV) v –5 spectrum advocated by Fisk and Gloeckler.

The series elastic shock absorber: tendon elasticity modulates energy dissipation by muscle during burst deceleration.

Science.gov (United States)

Konow, Nicolai; Roberts, Thomas J

2015-04-07

During downhill running, manoeuvring, negotiation of obstacles and landings from a jump, mechanical energy is dissipated via active lengthening of limb muscles. Tendon compliance provides a 'shock-absorber' mechanism that rapidly absorbs mechanical energy and releases it more slowly as the recoil of the tendon does work to stretch muscle fascicles. By lowering the rate of muscular energy dissipation, tendon compliance likely reduces the risk of muscle injury that can result from rapid and forceful muscle lengthening. Here, we examine how muscle-tendon mechanics are modulated in response to changes in demand for energy dissipation. We measured lateral gastrocnemius (LG) muscle activity, force and fascicle length, as well as leg joint kinematics and ground-reaction force, as turkeys performed drop-landings from three heights (0.5-1.5 m centre-of-mass elevation). Negative work by the LG muscle-tendon unit during landing increased with drop height, mainly owing to greater muscle recruitment and force as drop height increased. Although muscle strain did not increase with landing height, ankle flexion increased owing to increased tendon strain at higher muscle forces. Measurements of the length-tension relationship of the muscle indicated that the muscle reached peak force at shorter and likely safer operating lengths as drop height increased. Our results indicate that tendon compliance is important to the modulation of energy dissipation by active muscle with changes in demand and may provide a mechanism for rapid adjustment of function during deceleration tasks of unpredictable intensity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Factors influencing flow steadiness in laminar boundary layer shock interactions

Science.gov (United States)

Tumuklu, Ozgur; Levin, Deborah A.; Gimelshein, Sergey F.; Austin, Joanna M.

2016-11-01

The Direct Simulation Monte Carlo method has been used to model laminar shock wave boundary interactions of hypersonic flow over a 30/55-deg double-wedge and "tick-shaped" model configurations studied in the Hypervelocity Expansion Tube facility and T-ADFA free-piston shock tunnel, respectively. The impact of thermochemical effects on these interactions by changing the chemical composition from nitrogen to air as well as argon for a stagnation enthalpy of 8.0 MJ/kg flow are investigated using the 2-D wedge model. The simulations are found to reproduce many of the classic features related to Edney Type V strong shock interactions that include the attached, oblique shock formed over the first wedge, the detached bow shock from the second wedge, the separation zone, and the separation and reattachment shocks that cause complex features such as the triple point for both cases. However, results of a reacting air flow case indicate that the size of the separation length, and the movement of the triple point toward to the leading edge is much less than the nitrogen case.

Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review.

Science.gov (United States)

Moura, Carolina Soares; Lollo, Pablo Christiano Barboza; Morato, Priscila Neder; Amaya-Farfan, Jaime

2018-05-28

Interest in the heat shock proteins (HSPs), as a natural physiological toolkit of living organisms, has ranged from their chaperone function in nascent proteins to the remedial role following cell stress. As part of the defence system, HSPs guarantee cell tolerance against a variety of stressors, including exercise, oxidative stress, hyper and hypothermia, hyper and hypoxia and improper diets. For the past couple of decades, research on functional foods has revealed a number of substances likely to trigger cell protection through mechanisms that involve the induction of HSP expression. This review will summarize the occurrence of the most easily inducible HSPs and describe the effects of dietary proteins, peptides, amino acids, probiotics, high-fat diets and other food-derived substances reported to induce HSP response in animals and humans studies. Future research may clarify the mechanisms and explore the usefulness of this natural alternative of defense and the modulating mechanism of each substance.

On possible structures of normal ionizing shock waves in electromagnetic shock tubes

International Nuclear Information System (INIS)

Liberman, M.A.; Synakh, V.S.; Zakajdakhov, V.V.; Velikovich, A.L.

1982-01-01

The problem of possible structures of normal ionizing shock waves is studied. On the basis of the general theory of ionizing shock waves in magnetic fields, a similarity solution of the piston problem for an impenetrable piston and a magnetic piston is described and a numerical solution of the non-stationary piston problem is obtained. It is shown that precursor photo-ionization of the neutral gas by the radiation of the shock-heated gas is the dominant factor in shaping normal ionizing shock structures. In particular, it is shown that the strong overheating of atoms and ions in shock fronts is due to the tensor form of Ohm's law in the precursor region. (author)

Effects of Alfvénic Drift on Diffusive Shock Acceleration at Weak Cluster Shocks

Science.gov (United States)

Kang, Hyesung; Ryu, Dongsu

2018-03-01

Non-detection of γ-ray emission from galaxy clusters has challenged diffusive shock acceleration (DSA) of cosmic-ray (CR) protons at weak collisionless shocks that are expected to form in the intracluster medium. As an effort to address this problem, we here explore possible roles of Alfvén waves self-excited via resonant streaming instability during the CR acceleration at parallel shocks. The mean drift of Alfvén waves may either increase or decrease the scattering center compression ratio, depending on the postshock cross-helicity, leading to either flatter or steeper CR spectra. We first examine such effects at planar shocks, based on the transport of Alfvén waves in the small amplitude limit. For the shock parameters relevant to cluster shocks, Alfvénic drift flattens the CR spectrum slightly, resulting in a small increase of the CR acceleration efficiency, η. We then consider two additional, physically motivated cases: (1) postshock waves are isotropized via MHD and plasma processes across the shock transition, and (2) postshock waves contain only forward waves propagating along with the flow due to a possible gradient of CR pressure behind the shock. In these cases, Alfvénic drift could reduce η by as much as a factor of five for weak cluster shocks. For the canonical parameters adopted here, we suggest η ∼ 10‑4–10‑2 for shocks with sonic Mach number M s ≈ 2–3. The possible reduction of η may help ease the tension between non-detection of γ-rays from galaxy clusters and DSA predictions.

Force Factor Modulation in Electro Dynamic Loudspeakers

DEFF Research Database (Denmark)

Risbo, Lars; Agerkvist, Finn T.; Tinggaard, Carsten

2016-01-01

The relationship between the non-linear phenomenon of ’reluctance force’ and the position dependency of the voice coil inductance was established in 1949 by Cunningham, who called it ’magnetic attraction force’. This paper revisits Cunningham’s analysis and expands it into a generalised form...... that includes the frequency dependency and applies to coils with non-inductive (lossy) blocked impedance. The paper also demonstrates that Cunningham’s force can be explained physically as a modulation of the force factor which again is directly linked to modulation of the flux of the coil. A verification based...... on both experiments and simulations is presented along discussions of the impact of force factor modulation for various motor topologies. Finally, it is shown that the popular L2R2 coil impedance model does not correctly predict the force unless the new analysis is applied....

Destabilization and recovery of a yeast prion after mild heat shock.

Science.gov (United States)

Newnam, Gary P; Birchmore, Jennifer L; Chernoff, Yury O

2011-05-06

Yeast prion [PSI(+)] is a self-perpetuating amyloid of the translational termination factor Sup35. Although [PSI(+)] propagation is modulated by heat shock proteins (Hsps), high temperature was previously reported to have little or no effect on [PSI(+)]. Our results show that short-term exposure of exponentially growing yeast culture to mild heat shock, followed by immediate resumption of growth, leads to [PSI(+)] destabilization, sometimes persisting for several cell divisions after heat shock. Prion loss occurring in the first division after heat shock is preferentially detected in a daughter cell, indicating the impairment of prion segregation that results in asymmetric prion distribution between a mother cell and a bud. Longer heat shock or prolonged incubation in the absence of nutrients after heat shock led to [PSI(+)] recovery. Both prion destabilization and recovery during heat shock depend on protein synthesis. Maximal prion destabilization coincides with maximal imbalance between Hsp104 and other Hsps such as Hsp70-Ssa. Deletions of individual SSA genes increase prion destabilization and/or counteract recovery. The dynamics of prion aggregation during destabilization and recovery are consistent with the notion that efficient prion fragmentation and segregation require a proper balance between Hsp104 and other (e.g., Hsp70-Ssa) chaperones. In contrast to heat shock, [PSI(+)] destabilization by osmotic stressors does not always depend on cell proliferation and/or protein synthesis, indicating that different stresses may impact the prion via different mechanisms. Our data demonstrate that heat stress causes asymmetric prion distribution in a cell division and confirm that the effects of Hsps on prions are physiologically relevant. Copyright © 2011 Elsevier Ltd. All rights reserved.

BROAD N2H+ EMISSION TOWARD THE PROTOSTELLAR SHOCK L1157-B1

International Nuclear Information System (INIS)

Codella, C.; Fontani, F.; Gómez-Ruiz, A.; Vasta, M.; Viti, S.; Ceccarelli, C.; Lefloch, B.; Podio, L.; Benedettini, M.; Busquet, G.; Caselli, P.

2013-01-01

We present the first detection of N 2 H + toward a low-mass protostellar outflow, namely, the L1157-B1 shock, at ∼0.1 pc from the protostellar cocoon. The detection was obtained with the IRAM 30 m antenna. We observed emission at 93 GHz due to the J = 1-0 hyperfine lines. Analysis of this emission coupled with HIFI CHESS multiline CO observations leads to the conclusion that the observed N 2 H + (1-0) line originated from the dense (≥10 5 cm –3 ) gas associated with the large (20''-25'') cavities opened by the protostellar wind. We find an N 2 H + column density of a few 10 12 cm –2 corresponding to an abundance of (2-8) × 10 –9 . The N 2 H + abundance can be matched by a model of quiescent gas evolved for more than 10 4 yr, i.e., for more than the shock kinematical age (≅2000 yr). Modeling of C-shocks confirms that the abundance of N 2 H + is not increased by the passage of the shock. In summary, N 2 H + is a fossil record of the pre-shock gas, formed when the density of the gas was around 10 4 cm –3 , and then further compressed and accelerated by the shock

Nonrelativistic grey Sn-transport radiative-shock solutions

International Nuclear Information System (INIS)

Ferguson, J. M.; Morel, J. E.; Lowrie, R. B.

2017-01-01

We present semi-analytic radiative-shock solutions in which grey Sn-transport is used to model the radiation, and we include both constant cross sections and cross sections that depend on temperature and density. These new solutions solve for a variable Eddington factor (VEF) across the shock domain, which allows for interesting physics not seen before in radiative-shock solutions. Comparisons are made with the grey nonequilibrium-diffusion radiative-shock solutions of Lowrie and Edwards [1], which assumed that the Eddington factor is constant across the shock domain. It is our experience that the local Mach number is monotonic when producing nonequilibrium-diffusion solutions, but that this monotonicity may disappear while integrating the precursor region to produce Sn-transport solutions. For temperature- and density-dependent cross sections we show evidence of a spike in the VEF in the far upstream portion of the radiative-shock precursor. We show evidence of an adaptation zone in the precursor region, adjacent to the embedded hydrodynamic shock, as conjectured by Drake [2, 3], and also confirm his expectation that the precursor temperatures adjacent to the Zel’dovich spike take values that are greater than the downstream post-shock equilibrium temperature. We also show evidence that the radiation energy density can be nonmonotonic under the Zel’dovich spike, which is indicative of anti-diffusive radiation flow as predicted by McClarren and Drake [4]. We compare the angle dependence of the radiation flow for the Sn-transport and nonequilibriumdiffusion radiation solutions, and show that there are considerable differences in the radiation flow between these models across the shock structure. Lastly, we analyze the radiation flow to understand the cause of the adaptation zone, as well as the structure of the Sn-transport radiation-intensity solutions across the shock structure.

Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats.

Science.gov (United States)

Zhang, Fan; Luo, Jie; Min, Su; Ren, Li; Qin, Peipei

2016-07-01

This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

DEFF Research Database (Denmark)

Fex Svenningsen, Åsa; Loering, Svenja; Sørensen, Anna Lahn

2017-01-01

Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although...

Modulation of DNA binding by gene-specific transcription factors.

Science.gov (United States)

Schleif, Robert F

2013-10-01

The transcription of many genes, particularly in prokaryotes, is controlled by transcription factors whose activity can be modulated by controlling their DNA binding affinity. Understanding the molecular mechanisms by which DNA binding affinity is regulated is important, but because forming definitive conclusions usually requires detailed structural information in combination with data from extensive biophysical, biochemical, and sometimes genetic experiments, little is truly understood about this topic. This review describes the biological requirements placed upon DNA binding transcription factors and their consequent properties, particularly the ways that DNA binding affinity can be modulated and methods for its study. What is known and not known about the mechanisms modulating the DNA binding affinity of a number of prokaryotic transcription factors, including CAP and lac repressor, is provided.

Tuning the Fano factor of graphene via Fermi velocity modulation

Science.gov (United States)

Lima, Jonas R. F.; Barbosa, Anderson L. R.; Bezerra, C. G.; Pereira, Luiz Felipe C.

2018-03-01

In this work we investigate the influence of a Fermi velocity modulation on the Fano factor of periodic and quasi-periodic graphene superlattices. We consider the continuum model and use the transfer matrix method to solve the Dirac-like equation for graphene where the electrostatic potential, energy gap and Fermi velocity are piecewise constant functions of the position x. We found that in the presence of an energy gap, it is possible to tune the energy of the Fano factor peak and consequently the location of the Dirac point, by a modulation in the Fermi velocity. Hence, the peak of the Fano factor can be used experimentally to identify the Dirac point. We show that for higher values of the Fermi velocity the Fano factor goes below 1/3 at the Dirac point. Furthermore, we show that in periodic superlattices the location of Fano factor peaks is symmetric when the Fermi velocity vA and vB is exchanged, however by introducing quasi-periodicity the symmetry is lost. The Fano factor usually holds a universal value for a specific transport regime, which reveals that the possibility of controlling it in graphene is a notable result.

Corticosteroids in the treatment of dengue shock syndrome.

Science.gov (United States)

Rajapakse, Senaka; Rodrigo, Chaturaka; Maduranga, Sachith; Rajapakse, Anoja Chamarie

2014-01-01

Dengue infection causes significant morbidity and mortality in over 100 countries worldwide, and its incidence is on the rise. The pathophysiological basis for the development of severe dengue, characterized by plasma leakage and the "shock syndrome" are poorly understood. No specific treatment or vaccine is available, and careful monitoring and judicious administration of fluids forms the mainstay of management at present. It is postulated that vascular endothelial dysfunction, induced by cytokine and chemical mediators, is an important mechanism of plasma leakage. Although corticosteroids are potent modulators of the immune system, their role in pharmacological doses in modulating the purported immunological effects that take place in severe dengue has been a subject of controversy. The key evidence related to the role of corticosteroids for various manifestations of dengue are reviewed here. In summary, there is currently no high-quality evidence supporting the beneficial effects of corticosteroids for treatment of shock, prevention of serious complications, or increasing platelet counts. Non-randomized trials of corticosteroids given as rescue medication for severe shock have shown possible benefit. Nonetheless, the evidence base is small, and good-quality trials are lacking. We reiterate the need for well-designed and adequately powered randomized controlled trials of corticosteroids for the treatment of dengue shock.

On the low pressure shock initiation of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine based plastic bonded explosives

Science.gov (United States)

Vandersall, Kevin S.; Tarver, Craig M.; Garcia, Frank; Chidester, Steven K.

2010-05-01

In large explosive and propellant charges, relatively low shock pressures on the order of 1-2 GPa impacting large volumes and lasting tens of microseconds can cause shock initiation of detonation. The pressure buildup process requires several centimeters of shock propagation before shock to detonation transition occurs. In this paper, experimentally measured run distances to detonation for lower input shock pressures are shown to be much longer than predicted by extrapolation of high shock pressure data. Run distance to detonation and embedded manganin gauge pressure histories are measured using large diameter charges of six octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) based plastic bonded explosives (PBX's): PBX 9404; LX-04; LX-07; LX-10; PBX 9501; and EDC37. The embedded gauge records show that the lower shock pressures create fewer and less energetic "hot spot" reaction sites, which consume the surrounding explosive particles at reduced reaction rates and cause longer distances to detonation. The experimental data is analyzed using the ignition and growth reactive flow model of shock initiation in solid explosives. Using minimum values of the degrees of compression required to ignite hot spot reactions, the previously determined high shock pressure ignition and growth model parameters for the six explosives accurately simulate the much longer run distances to detonation and much slower growths of pressure behind the shock fronts measured during the shock initiation of HMX PBX's at several low shock pressures.

A Reverse Shock in GRB 160509A

Science.gov (United States)

Laskar, Tanmoy; Alexander, Kate D.; Berger, Edo; Fong, Wen-fai; Margutti, Raffaella; Shivvers, Isaac; Williams, Peter K. G.; Kopač, Drejc; Kobayashi, Shiho; Mundell, Carole; Gomboc, Andreja; Zheng, WeiKang; Menten, Karl M.; Graham, Melissa L.; Filippenko, Alexei V.

2016-12-01

We present the second multi-frequency radio detection of a reverse shock in a γ-ray burst. By combining our extensive radio observations of the Fermi-Large Area Telescope γ-ray burst 160509A at z = 1.17 up to 20 days after the burst with Swift X-ray observations and ground-based optical and near-infrared data, we show that the afterglow emission comprises distinct reverse shock and forward shock contributions: the reverse shock emission dominates in the radio band at ≲10 days, while the forward shock emission dominates in the X-ray, optical, and near-infrared bands. Through multi-wavelength modeling, we determine a circumburst density of {n}0≈ {10}-3 {{cm}}-3, supporting our previous suggestion that a low-density circumburst environment is conducive to the production of long-lasting reverse shock radiation in the radio band. We infer the presence of a large excess X-ray absorption column, N H ≈ 1.5 × 1022 {{cm}}-2, and a high rest-frame optical extinction, A V ≈ 3.4 mag. We identify a jet break in the X-ray light curve at {t}{jet}≈ 6 {days}, and thus derive a jet opening angle of {θ }{jet}≈ 4^\\circ , yielding a beaming-corrected kinetic energy and radiated γ-ray energy of {E}{{K}}≈ 4× {10}50 erg and {E}γ ≈ 1.3× {10}51 erg (1-104 keV, rest frame), respectively. Consistency arguments connecting the forward shocks and reverse shocks suggest a deceleration time of {t}{dec} ≈ 460 s ≈ T 90, a Lorentz factor of {{Γ }}({t}{dec})≈ 330, and a reverse-shock-to-forward-shock fractional magnetic energy density ratio of {R}{{B}}\\equiv {ɛ }{{B},{RS}}/{ɛ }{{B},{FS}}≈ 8. Our study highlights the power of rapid-response radio observations in the study of the properties and dynamics of γ-ray burst ejecta.

Energetic protons associated with a forward-reverse interplanetary shock pair at 1 A. U

Energy Technology Data Exchange (ETDEWEB)

Balogh, A [Imperial Coll. of Science and Technology, London (UK)

1977-10-01

A forward-reverse interplanetary shock was observed on 25 March 1969 by the magnetometer and plasma detector on the HEOS-1 satellite. This relatively rare event was described by Chao et al (1972) who concluded that the shock pair was formed at a distance 0.10 to 0.13 AU upstream of the Earth as a result of the interaction between a fast and a slow solar wind streams. Simultaneous observations of 1 MeV solar proton fluxes were also performed on HEOS-1. A characteristic intensity peak was observed as the forward shock passed by the spacecraft. The evolution of the proton intensity, together with a detailed analysis of anisotropies and pitch angle distributions show a complex dynamic picture of the effect of the forward shock on the ambient proton population. Significant changes in particle fluxes are seen to be correlated with fluctuations in the magnetic field. It is suggested that simple geometrical models of shock-assisted acceleration should be expanded to include the effect of magnetic fluctuations on particle fluxes. The interaction region limited by the forward and reverse shocks contained a large variety of magnetic fluctuations. Following the tangential discontinuity separating the fast solar wind stream from the preceding slow stream, a sunward flow was observed in the proton data, followed by a small but significant drop in intensity prior to the reverse shock.

Analytical model for fast-shock ignition

International Nuclear Information System (INIS)

Ghasemi, S. A.; Farahbod, A. H.; Sobhanian, S.

2014-01-01

A model and its improvements are introduced for a recently proposed approach to inertial confinement fusion, called fast-shock ignition (FSI). The analysis is based upon the gain models of fast ignition, shock ignition and considerations for the fast electrons penetration into the pre-compressed fuel to examine the formation of an effective central hot spot. Calculations of fast electrons penetration into the dense fuel show that if the initial electron kinetic energy is of the order ∼4.5 MeV, the electrons effectively reach the central part of the fuel. To evaluate more realistically the performance of FSI approach, we have used a quasi-two temperature electron energy distribution function of Strozzi (2012) and fast ignitor energy formula of Bellei (2013) that are consistent with 3D PIC simulations for different values of fast ignitor laser wavelength and coupling efficiency. The general advantages of fast-shock ignition in comparison with the shock ignition can be estimated to be better than 1.3 and it is seen that the best results can be obtained for the fuel mass around 1.5 mg, fast ignitor laser wavelength ∼0.3  micron and the shock ignitor energy weight factor about 0.25

Multiple shocks, coping and welfare consequences: natural disasters and health shocks in the Indian Sundarbans.

Science.gov (United States)

Mazumdar, Sumit; Mazumdar, Papiya Guha; Kanjilal, Barun; Singh, Prashant Kumar

2014-01-01

Based on a household survey in Indian Sundarbans hit by tropical cyclone Aila in May 2009, this study tests for evidence and argues that health and climatic shocks are essentially linked forming a continuum and with exposure to a marginal one, coping mechanisms and welfare outcomes triggered in the response is significantly affected. The data for this study is based on a cross-sectional household survey carried out during June 2010. The survey was aimed to assess the impact of cyclone Aila on households and consequent coping mechanisms in three of the worst-affected blocks (a sub-district administrative unit), viz. Hingalganj, Gosaba and Patharpratima. The survey covered 809 individuals from 179 households, cross cutting age and gender. A separate module on health-seeking behaviour serves as the information source of health shocks defined as illness episodes (ambulatory or hospitalized) experienced by household members. Finding reveals that over half of the households (54%) consider that Aila has dealt a high, damaging impact on their household assets. Result further shows deterioration of health status in the period following the incidence of Aila. Finding suggests having suffered multiple shocks increases the number of adverse welfare outcomes by 55%. Whereas, suffering either from the climatic shock (33%) or the health shock (25%) alone increases such risks by a much lesser extent. The multiple-shock households face a significantly higher degree of difficulty to finance expenses arising out of health shocks, as opposed to their counterparts facing only the health shock. Further, these households are more likely to finance the expenses through informal loans and credit from acquaintances or moneylenders. This paper presented empirical evidence on how natural and health shocks mutually reinforce their resultant impact, making coping increasingly difficult and present significant risks of welfare loss, having short as well as long-run development manifestations.

Heat shock protein 90 in neurodegenerative diseases

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Rodina Anna

2010-06-01

Full Text Available Abstract Hsp90 is a molecular chaperone with important roles in regulating pathogenic transformation. In addition to its well-characterized functions in malignancy, recent evidence from several laboratories suggests a role for Hsp90 in maintaining the functional stability of neuronal proteins of aberrant capacity, whether mutated or over-activated, allowing and sustaining the accumulation of toxic aggregates. In addition, Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1, the master regulator of the heat shock response, mechanism that cells use for protection when exposed to conditions of stress. These biological functions therefore propose Hsp90 inhibition as a dual therapeutic modality in neurodegenerative diseases. First, by suppressing aberrant neuronal activity, Hsp90 inhibitors may ameliorate protein aggregation and its associated toxicity. Second, by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity. This mini-review will summarize our current knowledge on Hsp90 in neurodegeneration and will focus on the potential beneficial application of Hsp90 inhibitors in neurodegenerative diseases.

Class A CpG Oligonucleotide Priming Rescues Mice from Septic Shock via Activation of Platelet-Activating Factor Acetylhydrolase

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Yoshinari Yamamoto

2017-08-01

Full Text Available Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A1585 strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A1585 rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation. Furthermore, CpG-A1585 improved endotoxin shock induced by lipopolysaccharide, which comprises the cell wall of Gram-negative bacteria and inhibits inflammatory responses induced by cytokines such as interleukin-6 and tumor necrosis factor-α. These results suggest that CpG-A1585 is a potential therapeutic target to prevent sepsis-related induction of PAF.

Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc

Directory of Open Access Journals (Sweden)

Marks David R

2009-01-01

Full Text Available Abstract Background Neurotrophins are important regulators of growth and regeneration, and acutely, they can modulate the activity of voltage-gated ion channels. Previously we have shown that acute brain-derived neurotrophic factor (BDNF activation of neurotrophin receptor tyrosine kinase B (TrkB suppresses the Shaker voltage-gated potassium channel (Kv1.3 via phosphorylation of multiple tyrosine residues in the N and C terminal aspects of the channel protein. It is not known how adaptor proteins, which lack catalytic activity, but interact with members of the neurotrophic signaling pathway, might scaffold with ion channels or modulate channel activity. Results We report the co-localization of two adaptor proteins, neuronal Src homology and collagen (nShc and growth factor receptor-binding protein 10 (Grb10, with Kv1.3 channel as demonstrated through immunocytochemical approaches in the olfactory bulb (OB neural lamina. To further explore the specificity and functional ramification of adaptor/channel co-localization, we performed immunoprecipitation and Western analysis of channel, kinase, and adaptor transfected human embryonic kidney 293 cells (HEK 293. nShc formed a direct protein-protein interaction with Kv1.3 that was independent of BDNF-induced phosphorylation of Kv1.3, whereas Grb10 did not complex with Kv1.3 in HEK 293 cells. Both adaptors, however, co-immunoprecipitated with Kv1.3 in native OB. Grb10 was interestingly able to decrease the total expression of Kv1.3, particularly at the membrane surface, and subsequently eliminated the BDNF-induced phosphorylation of Kv1.3. To examine the possibility that the Src homology 2 (SH2 domains of Grb10 were directly binding to basally phosphorylated tyrosines in Kv1.3, we utilized point mutations to substitute multiple tyrosine residues with phenylalanine. Removal of the tyrosines 111–113 and 449 prevented Grb10 from decreasing Kv1.3 expression. In the absence of either adaptor protein

Heat shock response improves heterologous protein secretion in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Hou, Jin; Österlund, Tobias; Liu, Zihe

2013-01-01

The yeast Saccharomyces cerevisiae is a widely used platform for the production of heterologous proteins of medical or industrial interest. However, heterologous protein productivity is often low due to limitations of the host strain. Heat shock response (HSR) is an inducible, global, cellular...... stress response, which facilitates the cell recovery from many forms of stress, e.g., heat stress. In S. cerevisiae, HSR is regulated mainly by the transcription factor heat shock factor (Hsf1p) and many of its targets are genes coding for molecular chaperones that promote protein folding and prevent...... the accumulation of mis-folded or aggregated proteins. In this work, we over-expressed a mutant HSF1 gene HSF1-R206S which can constitutively activate HSR, so the heat shock response was induced at different levels, and we studied the impact of HSR on heterologous protein secretion. We found that moderate and high...

The stress protein heat shock cognate 70 (Hsc70) inhibits the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel.

Science.gov (United States)

Iftinca, Mircea; Flynn, Robyn; Basso, Lilian; Melo, Helvira; Aboushousha, Reem; Taylor, Lauren; Altier, Christophe

2016-01-01

Specialized cellular defense mechanisms prevent damage from chemical, biological, and physical hazards. The heat shock proteins have been recognized as key chaperones that maintain cell survival against a variety of exogenous and endogenous stress signals including noxious temperature. However, the role of heat shock proteins in nociception remains poorly understood. We carried out an expression analysis of the constitutively expressed 70 kDa heat-shock cognate protein, a member of the stress-induced HSP70 family in lumbar dorsal root ganglia from a mouse model of Complete Freund's Adjuvant-induced chronic inflammatory pain. We used immunolabeling of dorsal root ganglion neurons, behavioral analysis and patch clamp electrophysiology in both dorsal root ganglion neurons and HEK cells transfected with Hsc70 and Transient Receptor Potential Channels to examine their functional interaction in heat shock stress condition. We report an increase in protein levels of Hsc70 in mouse dorsal root ganglia, 3 days post Complete Freund's Adjuvant injection in the hind paw. Immunostaining of Hsc70 was observed in most of the dorsal root ganglion neurons, including the small size nociceptors immunoreactive to the TRPV1 channel. Standard whole-cell patch-clamp technique was used to record Transient Receptor Potential Vanilloid type 1 current after exposure to heat shock. We found that capsaicin-evoked currents are inhibited by heat shock in dorsal root ganglion neurons and transfected HEK cells expressing Hsc70 and TRPV1. Blocking Hsc70 with matrine or spergualin compounds prevented heat shock-induced inhibition of the channel. We also found that, in contrast to TRPV1, both the cold sensor channels TRPA1 and TRPM8 were unresponsive to heat shock stress. Finally, we show that inhibition of TRPV1 depends on the ATPase activity of Hsc70 and involves the rho-associated protein kinase. Our work identified Hsc70 and its ATPase activity as a central cofactor of TRPV1 channel function

Design and testing of a shock absorber for a type 1 container

International Nuclear Information System (INIS)

Sappok, M.; Beine, B.; Rittscher, D.

1993-01-01

A shock-absorber will be required for a rad. waste 'Konrad' type 1 container made of ductile cast iron whenever it will be used as a type B container according to the IAEA-Regulations for the Safe Transport of Radioactive materials. The shock-absorber has to protect the type B container during shipping such as to withstand the accident scenarios that are covered by the IAEA-Regulation tests without substantial loss of its shielding and tightness functions. The designation as type 1 container originates from German regulations for the intermediate storage site Gorleben and the final depository Konrad-mine. These regulations call for the limits on outside dimensions of 1700 mm in length, 1600 mm in width and 1450 mm in height as well as for a limit of 20 Mg on total weight without shock-absorber. The relatively simple design method for the shock-absorber has been validated by the test results. It can be extended to other materials and designs for shock-absorbers if reliable force-displacement-diagrams are available for the structural elements from which the absorbed energy and the displacements can be calculated by integration. In order to account for the dynamic effects, the better approximation of the true duration of the impact would be helpful. The present limit of 0.5 R p0,2 on the nominal stresses should be discussed because the large number of tests on containers made of ductile cast iron that have been performed up to now have shown a substantial level of conservatism on this respect. The sharply tapered pipes on edge Kl of the shock-absorbers should be replaced by pipe bends. This will result in smaller accelerations and in an even higher level of protection of the container than effected by the tested shock-absorber

A cross-country analysis of climate shocks and smallholder food insecurity.

Science.gov (United States)

Niles, Meredith T; Salerno, Jonathan D

2018-01-01

Future climate changes will affect smallholder farmers in the developing world, posing threats to household food security. Nevertheless, there remains limited comparable evidence across multiple countries and regions regarding the global extent of climate shocks affecting smallholder food security. We examine data from 5,299 household surveys across 15 countries in Latin America, Africa and South Asia to assess the extent of climate shocks and their association with food insecurity, as well as what strategies may help buffer against climate shocks. We find that 71% of households reported experiencing a climate shock in the previous five years. Fifty-four percent reported experiencing food insecurity during one or more months annually. A multilevel statistical model estimated factors correlated with food insecurity as well as factors correlated with food insecurity among households that had experienced a climate shock. Households that reported experiencing a climate shock were 1.73 times more likely to be food insecure. As well, larger and poorer households were associated with higher odds of food insecurity while using pesticides, keeping large livestock, and being more educated are associated with lower odds of food insecurity. Among households that had experienced a climate shock, additional factors are correlated with lower odds of food insecurity when compared to otherwise similar households: use of fertilizers, pesticides, veterinary medicines, large livestock, and household assets. Together, these results demonstrate the extent of existing climate shocks affecting smallholder farmers and how interventions may potentially support adaptation and reduce food insecurity.

A cross-country analysis of climate shocks and smallholder food insecurity.

Directory of Open Access Journals (Sweden)

Meredith T Niles

Full Text Available Future climate changes will affect smallholder farmers in the developing world, posing threats to household food security. Nevertheless, there remains limited comparable evidence across multiple countries and regions regarding the global extent of climate shocks affecting smallholder food security. We examine data from 5,299 household surveys across 15 countries in Latin America, Africa and South Asia to assess the extent of climate shocks and their association with food insecurity, as well as what strategies may help buffer against climate shocks. We find that 71% of households reported experiencing a climate shock in the previous five years. Fifty-four percent reported experiencing food insecurity during one or more months annually. A multilevel statistical model estimated factors correlated with food insecurity as well as factors correlated with food insecurity among households that had experienced a climate shock. Households that reported experiencing a climate shock were 1.73 times more likely to be food insecure. As well, larger and poorer households were associated with higher odds of food insecurity while using pesticides, keeping large livestock, and being more educated are associated with lower odds of food insecurity. Among households that had experienced a climate shock, additional factors are correlated with lower odds of food insecurity when compared to otherwise similar households: use of fertilizers, pesticides, veterinary medicines, large livestock, and household assets. Together, these results demonstrate the extent of existing climate shocks affecting smallholder farmers and how interventions may potentially support adaptation and reduce food insecurity.

Pregnane and Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-jun

Energy Technology Data Exchange (ETDEWEB)

Kumari, Sangeeta; Saradhi, Mallampati; Rana, Manjul; Chatterjee, Swagata [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India); Aumercier, Marc [IRI, CNRS USR 3078, Université de Lille-Nord de France, Parc CNRS de la Haute Borne, 50 Avenue de Halley, BP 70478, 59658 Villeneuve d’Ascq Cedex (France); Mukhopadhyay, Gauranga [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India); Tyagi, Rakesh K., E-mail: rktyagi@yahoo.com [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India)

2015-01-15

Nuclear receptor PXR is predominantly expressed in liver and intestine. Expression of PXR is observed to be dysregulated in various metabolic disorders indicating its involvement in disease development. However, information available on mechanisms of PXR self-regulation is fragmentary. The present investigation identifies some of the regulatory elements responsible for its tight regulation and low cellular expression. Here, we report that the PXR-promoter is a target for some key transcription factors like PU.1/Ets-1, Pax5, LEF-1 and c-Jun. Interestingly, we observed that PXR-promoter responsiveness to Pax5, LEF-1 and c-Jun, is considerably enhanced by Ets transcription factors (PU.1 and Ets-1). Co-transfection of cells with Ets-1, LEF-1 and c-Jun increased PXR-promoter activity by 5-fold and also induced expression of endogenous human PXR. Site-directed mutagenesis and transfection studies revealed that two Ets binding sites and two of the three LEF binding sites in the PXR-promoter are functional and have a positive effect on PXR transcription. Results suggest that expression of Ets family members, in conjunction with Pax5, LEF-1 and c-Jun, lead to coordinated up-regulation of PXR gene transcription. Insights obtained on the regulation of PXR gene have relevance in offering important cues towards normal functioning as well as development of several metabolic disorders via PXR signaling. - Highlights: • The study identified cis-regulatory elements in the nuclear receptor PXR promoter. • Several trans-acting factors modulating the PXR-promoter have been identified. • PU.1/Ets-1, Pax5, LEF-1, c-Jun, LyF-VI and NF-1 act as modulators of the PXR-promoter. • Ets-1 in conjunction with LEF-1 and c-Jun exhibit 5-fold activation of the PXR-promoter. • Insights into PXR-regulation have relevance in normal and pathological conditions.

Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats

Energy Technology Data Exchange (ETDEWEB)

Zhang, Y.P.; Niu, C.Y.; Zhao, Z.G.; Zhang, L.M.; Si, Y.H. [Institute of Microcirculation, Hebei North University, Hebei (China)

2013-08-10

Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40±2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca{sup 2+} were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca{sup 2+} at various concentrations. Maximum contractility (E{sub max}) in the shock group increased with NE (from 0.179±0.038 to 0.440±0.177 g/mg, P<0.05) and Ca{sup 2+} (from 0.515±0.043 to 0.646±0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca{sup 2+} at various concentrations in the shock+drainage group (from 0.744±0.187 to 0.570±0.143 g/mg in E{sub max} for NE and from 0.729±0.037 to 0.645±0.056 g/mg in E{sub max} for Ca{sup 2+}, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.

Influence of the vaginal microbiota on toxic shock syndrome toxin 1 production by Staphylococcus aureus.

Science.gov (United States)

MacPhee, Roderick A; Miller, Wayne L; Gloor, Gregory B; McCormick, John K; Hammond, Jo-Anne; Burton, Jeremy P; Reid, Gregor

2013-03-01

Menstrual toxic shock syndrome (TSS) is a serious illness that afflicts women of premenopausal age worldwide and arises from vaginal infection by Staphylococcus aureus and concurrent production of toxic shock syndrome toxin-1 (TSST-1). Studies have illustrated the capacity of lactobacilli to reduce S. aureus virulence, including the capacity to suppress TSST-1. We hypothesized that an aberrant microbiota characteristic of pathogenic bacteria would induce the increased production of TSST-1 and that this might represent a risk factor for the development of TSS. A S. aureus TSST-1 reporter strain was grown in the presence of vaginal swab contents collected from women with a clinically healthy vaginal status, women with an intermediate status, and those diagnosed with bacterial vaginosis (BV). Bacterial supernatant challenge assays were also performed to test the effects of aerobic vaginitis (AV)-associated pathogens toward TSST-1 production. While clinical samples from healthy and BV women suppressed toxin production, in vitro studies demonstrated that Streptococcus agalactiae and Enterococcus spp. significantly induced TSST-1 production, while some Lactobacillus spp. suppressed it. The findings suggest that women colonized by S. aureus and with AV, but not BV, may be more susceptible to menstrual TSS and would most benefit from prophylactic treatment.

Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock

Directory of Open Access Journals (Sweden)

Charchaflieh J

2012-07-01

Full Text Available Jean Charchaflieh,1,2 Georges I Labaze,1 Pulsar Li,1 Holly Van Remmen,3 Haekyung Lee,1 Helen Stutz,1 Arlan Richardson,3 Asher Emanuel,1 Ming Zhang1,41Department of Anesthesiology, State University of New York (SUNY Downstate Medical Center, New York, NY, USA; 2Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 3Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 4Department of Cell Biology, State University of New York (SUNY Downstate Medical Center, New York, NY, USABackground: Protective effects of the antioxidant enzyme Cu-Zn superoxide dismutase (SOD1 against endotoxic shock have not been demonstrated in animal models. We used a murine model to investigate whether overexpression of SOD1 protects against endotoxic shock, and whether the genetic background of SOD1 affects its effective protective effects and susceptibility to endotoxic shock.Methods: Transgenic (tg mice overexpressing human SOD1 and control mice were divided into four groups based on their genetic background: (1 tg mice with mixed genetic background (tg-JAX; (2 wild-type (WT littermates of tg-JAX strain (WT-JAX; (3 tg mice with C57BL/6J background (tg-TX; (4 WT littermates of tg-TX strain (WT-TX. Activity of SOD1 in the intestine, heart, and liver of tg and control mice was confirmed using a polyacrylamide activity gel. Endotoxic shock was induced by intraperitoneal injection of lipopolysaccharide. Survival rates over 120 hours (mean, 95% confidence interval were analyzed using Kaplan–Meier survival curves.Results: Human SOD1 enzymatic activities were significantly higher in the intestine, heart, and liver of both tg strains (tg-JAX and tg-TX compared with their WT littermates (WT-JAX and WT-TX, respectively. Interestingly, the endogenous SOD1 activities in tg-JAX mice were decreased compared with their WT littermates (WT-JAX, but such aberrant changes were not

Risk shocks and housing markets

OpenAIRE

Dorofeenko, Viktor; Lee, Gabriel S.; Salyer, Kevin D.

2010-01-01

Abstract: This paper analyzes the role of uncertainty in a multi-sector housing model with financial frictions. We include time varying uncertainty (i.e. risk shocks) in the technology shocks that affect housing production. The analysis demonstratesthat risk shocks to the housing production sector are a quantitatively important impulse mechanism for the business cycle. Also, we demonstrate that bankruptcy costs act as an endogenous markup factor in housing prices; as a consequence, the volati...

Shocks inside CMEs: A survey of properties from 1997 to 2006

Science.gov (United States)

Lugaz, N.; Farrugia, C. J.; Smith, C. W.; Paulson, K.

2015-04-01

We report on 49 fast-mode forward shocks propagating inside coronal mass ejections (CMEs) as measured by Wind and ACE at 1 AU from 1997 to 2006. Compared to typical CME-driven shocks, these shocks propagate in different upstream conditions, where the median upstream Alfvén speed is 85 km s-1, the proton β = 0.08 and the magnetic field strength is 8 nT. These shocks are fast with a median speed of 590 km s-1 but weak with a median Alfvénic Mach number of 1.9. They typically compress the magnetic field and density by a factor of 2-3. The most extreme upstream conditions found were a fast magnetosonic speed of 230 km s-1, a plasma β of 0.02, upstream solar wind speed of 740 km s-1 and density of 0.5 cm-3. Nineteen of these complex events were associated with an intense geomagnetic storm (peak Dst under -100 nT) within 12 h of the shock detection at Wind, and 15 were associated with a drop of the storm time Dst index of more than 50 nT between 3 and 9 h after shock detection. We also compare them to a sample of 45 shocks propagating in more typical upstream conditions. We show the average property of these shocks through a superposed epoch analysis, and we present some analytical considerations regarding the compression ratios of shocks in low β regimes. As most of these shocks are measured in the back half of a CME, we conclude that about half the shocks may not remain fast-mode shocks as they propagate through an entire CME due to the large upstream and magnetosonic speeds.

AKIP1 expression modulates mitochondrial function in rat neonatal cardiomyocytes

NARCIS (Netherlands)

Yu, Hongjuan; Tigchelaar, Wardit; Koonen, Debby P. Y.; Patel, Hemal H.; de Boer, Rudolf A.; van Gilst, Wiek H.; Westenbrink, B. Daan; Sillje, Herman H. W.

2013-01-01

A kinase interacting protein 1 (AKIP1) is a molecular regulator of protein kinase A and nuclear factor kappa B signalling. Recent evidence suggests AKIP1 is increased in response to cardiac stress, modulates acute ischemic stress response, and is localized to mitochondria in cardiomyocytes. The

Modulation of radiosensitivity by growth factors

International Nuclear Information System (INIS)

Paris, F.

2013-01-01

The full text of the publication follows. For the past 70 years, radiotherapy protocols were defined to target and kill cancer cells. New research developments showed that the tissue or tumor radiosensitivities might be directly modulated by its own microenvironment. Between all the micro-environmental cells, endothelial cells are playing a unique role due to the need of angio-genesis for tumor genesis and to the microvascular endothelial cell apoptosis involved in acute normal tissue and tumor radiosensitivities. Both endothelial behaviours may be controlled by specific growth factors secreted by tumor cells. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two cytokines involved in angio genesis and endothelial cell survival. Because radiation exposure develops opposite molecular and cellular responses by inhibiting proliferation and by enhancing apoptosis, inhibiting these cytokines has been proposed as a relevant strategy to improve radiotherapy efficiency. Drugs or antibody against VEGF, or other growth factors have been used with success to limit endothelial cell resistance, but also to transiently normalize of blood vessels to improve oxygen distribution into the tumor. However, better characterisation of the role of the cytokines will help to better improve the strategy of the use of their antagonists. We demonstrate that bFGF or sphingosin 1 phosphate (S1P), a lipid endothelial growth factor, protects endothelial cells from radiation stress by inhibiting the pre-mitotic apoptosis through enhancement of pro-survival molecular cascade, such as the Pi3K/AKT pathway, but not post-mitotic death. This discrepancy allowed a specific use of S1P as pharmacological drug protecting quiescent endothelial cells, present in normal tissue blood vessels, but not in proliferating angiogenic blood vessels, majority present in tumor blood vessel. In vivo studies are underway. (author)

Heat shock-induced interactions among nuclear HSFs detected by fluorescence cross-correlation spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Pack, Chan-Gi, E-mail: changipack@amc.seoul.kr [Asan Institute for Life Sciences, University of Ulsan, College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Ahn, Sang-Gun [Dept. of Pathology, College of Dentistry, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of)

2015-07-31

The cellular response to stress is primarily controlled in cells via transcriptional activation by heat shock factor 1 (HSF1). HSF1 is well-known to form homotrimers for activation upon heat shock and subsequently bind to target DNAs, such as heat-shock elements, by forming stress granules. A previous study demonstrated that nuclear HSF1 and HSF2 molecules in live cells interacted with target DNAs on the stress granules. However, the process underlying the binding interactions of HSF family in cells upon heat shock remains unclear. This study demonstrate for the first time that the interaction kinetics among nuclear HSF1, HSF2, and HSF4 upon heat shock can be detected directly in live cells using dual color fluorescence cross-correlation spectroscopy (FCCS). FCCS analyses indicated that the binding between HSFs was dramatically changed by heat shock. Interestingly, the recovery kinetics of interaction between HSF1 molecules after heat shock could be represented by changes in the relative interaction amplitude and mobility. - Highlights: • The binding interactions among nuclear HSFs were successfully detected. • The binding kinetics between HSF1s during recovery was quantified. • HSF2 and HSF4 strongly formed hetero-complex, even before heat shock. • Nuclear HSF2 and HSF4 bound to HSF1 only after heat shock.

RAPID COSMIC-RAY ACCELERATION AT PERPENDICULAR SHOCKS IN SUPERNOVA REMNANTS

Energy Technology Data Exchange (ETDEWEB)

Takamoto, Makoto; Kirk, John G., E-mail: mtakamoto@eps.s.u-tokyo.ac.jp, E-mail: john.kirk@mpi-hd.mpg.de [Max-Planck-Institut für Kernphysik, Postfach 103980, D-69029 Heidelberg (Germany)

2015-08-10

Perpendicular shocks are shown to be rapid particle accelerators that perform optimally when the ratio u{sub s} of the shock speed to the particle speed roughly equals the ratio 1/η of the scattering rate to the gyro frequency. We use analytical methods and Monte-Carlo simulations to solve the kinetic equation that governs the anisotropy generated at these shocks, and find, for ηu{sub s} ≈ 1, that the spectral index softens by unity and the acceleration time increases by a factor of two compared to the standard result of the diffusive shock acceleration theory. These results provide a theoretical basis for the 30 year old conjecture that a supernova exploding into the wind of a Wolf–Rayet star may accelerate protons to an energy exceeding 10{sup 15} eV.

Influenza A/H1N1 septic shock in a patient with systemic lupus erythematosus. A case report

Directory of Open Access Journals (Sweden)

Tselios Konstantinos

2011-12-01

Full Text Available Abstract Background Immunocompromised patients, such as systemic lupus erythematosus (SLE sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. Case Presentation In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU discharge. Conclusions To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement.

The Heliospheric Termination Shock

Science.gov (United States)

Jokipii, J. R.

2013-06-01

The heliospheric termination shock is a vast, spheroidal shock wave marking the transition from the supersonic solar wind to the slower flow in the heliosheath, in response to the pressure of the interstellar medium. It is one of the most-important boundaries in the outer heliosphere. It affects energetic particles strongly and for this reason is a significant factor in the effects of the Sun on Galactic cosmic rays. This paper summarizes the general properties and overall large-scale structure and motions of the termination shock. Observations over the past several years, both in situ and remote, have dramatically revised our understanding of the shock. The consensus now is that the shock is quite blunt, is with the front, blunt side canted at an angle to the flow direction of the local interstellar plasma relative to the Sun, and is dynamical and turbulent. Much of this new understanding has come from remote observations of energetic charged particles interacting with the shock, radio waves and radiation backscattered from interstellar neutral atoms. The observations and the implications are discussed.

GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells.

Science.gov (United States)

Vaziri-Gohar, Ali; Houston, Kevin D

2016-02-15

Tamoxifen, a selective estrogen receptor modulator, is a commonly prescribed adjuvant therapy for estrogen receptor-α (ERα)-positive breast cancer patients. To determine if extracellular factors contribute to the modulation of IGF-1 signaling after tamoxifen treatment, MCF-7 cells were treated with IGF-1 in conditioned medium (CM) obtained from 4-OHT-treated MCF-7 cells and the accumulation of phospho-Akt (S473) was measured. CM inhibited IGF-1-dependent cell signaling and suggesting the involvement of extracellular factors (ie. IGFBPs). A significant increase in IGFBP-1 mRNA and extracellular IGFBP-1 protein was observed in 4-OHT-treated MCF-7 cells. Knockdown experiments demonstrated that both GPER1 and CREB mediate IGFBP-1 induction. Furthermore, experiments showed that 4-OHT-dependent IGFBP-1 transcription is downstream of GPER1-activation in breast cancer cells. Additionally, neutralization and knockdown experiments demonstrated a role for IGFBP-1 in the observed inhibition of IGF-1 signaling. These results suggested that 4-OHT inhibits IGF-1 signaling via GPER1 and CREB mediated extracellular IGFBP-1 accumulation in breast cancer cells. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Immune and cell modulation by amino acids.

Science.gov (United States)

Roth, Erich

2007-10-01

Sir David Cuthbertson was the first to define metabolic alterations in post-aggression syndrome (PAS). From basic measurements of nitrogen loss and total protein synthesis/degradation, the current research has moved to genomics, proteomics and metabolomics. In this respect, first evidence was accumulated for the influence of acute catabolism, immobilisation by bed rest and sarcopenia of old age on the muscle-cell genome and proteome. Moreover, in post-aggression syndrome specific amino acids such as glutamine, arginine, glycine, taurine, tryptophan and cysteine are used for cell and immune modulation. Our laboratory has focused on the regulative capacity of glutamine. Glutamine deficiency as found in post-aggression syndrome reduces lymphocyte proliferation, alters monocyte/macrophage activity, decreases the formation of heat-shock proteins, stimulates cell apoptosis, shifts the cellular redox potential by altering the glutathione synthesis and increases the activity of the AMPK system. Investigating the molecular effect of glutamine on Hsp 70 induction, we tested the glutamine dependence on the formation of transfer-RNA and of heat-shock factor 1 (HSF 1), and on transcription and translation of Hsp 70. We could demonstrate that glutamine stabilises the mRNA of Hsp 70 thereby prolonging its half-life. The lecture also discusses the principal molecular targets of administered arginine, glycine, cysteine, taurine and tryptophan.

STEREO interplanetary shocks and foreshocks

Energy Technology Data Exchange (ETDEWEB)

Blanco-Cano, X. [Instituto de Geofisica, UNAM, CU, Coyoacan 04510 DF (Mexico); Kajdic, P. [IRAP-University of Toulouse, CNRS, Toulouse (France); Aguilar-Rodriguez, E. [Instituto de Geofisica, UNAM, Morelia (Mexico); Russell, C. T. [ESS and IGPP, University of California, Los Angeles, 603 Charles Young Drive, Los Angeles, CA 90095 (United States); Jian, L. K. [NASA Goddard Space Flight Center, Greenbelt, MD and University of Maryland, College Park, MD (United States); Luhmann, J. G. [SSL, University of California Berkeley (United States)

2013-06-13

We use STEREO data to study shocks driven by stream interactions and the waves associated with them. During the years of the extended solar minimum 2007-2010, stream interaction shocks have Mach numbers between 1.1-3.8 and {theta}{sub Bn}{approx}20-86 Degree-Sign . We find a variety of waves, including whistlers and low frequency fluctuations. Upstream whistler waves may be generated at the shock and upstream ultra low frequency (ULF) waves can be driven locally by ion instabilities. The downstream wave spectra can be formed by both, locally generated perturbations, and shock transmitted waves. We find that many quasiperpendicular shocks can be accompanied by ULF wave and ion foreshocks, which is in contrast to Earth's bow shock. Fluctuations downstream of quasi-parallel shocks tend to have larger amplitudes than waves downstream of quasi-perpendicular shocks. Proton foreshocks of shocks driven by stream interactions have extensions dr {<=}0.05 AU. This is smaller than foreshock extensions for ICME driven shocks. The difference in foreshock extensions is related to the fact that ICME driven shocks are formed closer to the Sun and therefore begin to accelerate particles very early in their existence, while stream interaction shocks form at {approx}1 AU and have been producing suprathermal particles for a shorter time.

STEREO interplanetary shocks and foreshocks

International Nuclear Information System (INIS)

Blanco-Cano, X.; Kajdič, P.; Aguilar-Rodríguez, E.; Russell, C. T.; Jian, L. K.; Luhmann, J. G.

2013-01-01

We use STEREO data to study shocks driven by stream interactions and the waves associated with them. During the years of the extended solar minimum 2007-2010, stream interaction shocks have Mach numbers between 1.1-3.8 and θ Bn ∼20-86°. We find a variety of waves, including whistlers and low frequency fluctuations. Upstream whistler waves may be generated at the shock and upstream ultra low frequency (ULF) waves can be driven locally by ion instabilities. The downstream wave spectra can be formed by both, locally generated perturbations, and shock transmitted waves. We find that many quasiperpendicular shocks can be accompanied by ULF wave and ion foreshocks, which is in contrast to Earth's bow shock. Fluctuations downstream of quasi-parallel shocks tend to have larger amplitudes than waves downstream of quasi-perpendicular shocks. Proton foreshocks of shocks driven by stream interactions have extensions dr ≤0.05 AU. This is smaller than foreshock extensions for ICME driven shocks. The difference in foreshock extensions is related to the fact that ICME driven shocks are formed closer to the Sun and therefore begin to accelerate particles very early in their existence, while stream interaction shocks form at ∼1 AU and have been producing suprathermal particles for a shorter time.

Technology shocks matter

OpenAIRE

Jonas D. M. Fisher

2002-01-01

This paper uses the neoclassical growth model to identify the effects of technological change on the US business cycle. In the model there are two sources of technological change: neutral, which effects the production of all goods homogeneously, and investment-specific. Investment-specific shocks are the unique source of the secular trend in the real price of investment goods, while shocks to both kinds of technology are the only factors which affect labor productivity in the long run. Consis...

Nonequilibrium effects on shock-layer radiometry during earth entry.

Science.gov (United States)

Arnold, J. O.; Whiting, E. E.

1973-01-01

Radiative enhancement factors for the CN violet and N2(+) first negative band systems caused by nonequilibrium thermochemistry in the shock layer of a blunt-nosed vehicle during earth entry are reported. The results are based on radiometric measurements obtained with the aid of a combustion-driven shock tube. The technique of converting the shock-tube measurements into predictions of the enhancement factors for the blunt-body case is described, showing it to be useful for similar applications of other shock-tube measurements.

The CHESS survey of the L1157-B1 bow-shock: Dissecting the water content

Science.gov (United States)

Busquet, Gemma; Lefloch, Bertrand; Benedettini, Milena; Ceccarelli, Cecilia; Codella, Claudio; Cabrit, Sylvie; Nisini, Brunella; Viti, Serena; Gómez-Ruiz, Arturo; Gusdorf, Antoine; Di Giorgio, Anna Maria; Wiesenfeld, Laurent

2013-07-01

Molecular outflows powered by young protostars strongly affect the kinematics and chemistry of the natal molecular cloud through strong shocks, resulting in an increase of the abundance of several species. In particular, water is a powerful tracer of shocked material due to its sensitivity to both physical conditions and chemical processes. The observations of the "Chemical Herschel Survey of Star forming regions" (CHESS) key program towards the shock region L1157-B1 offered a unique and comprehensive view of the water emission in a typical protostellar bow shock across the submillimeter and far-infrared window. A grand total of 13 water lines have been detected with the PACS and HIFI instruments, probing a wide range of excitation conditions and providing us with a detailed picture on both the kinematics and the spatial distribution of water emission. Several gas components have been identified coexisting in the L1157-B1 shock region. Large Velocity Gradient (LVG) analysis reveals that these components have different excitation conditions: i) a warm (T~250 K) and dense (n(H2)~10^6 cm-3) gas component seen also with the CO lines and associated with the partly dissociative shock produced by the impact of the protostellar jet against the bow shock; ii) a compact (size~5''), hot (T~700 K), and less dense (n(H2)~10^4 cm-3) gas component, and iii) an extended component associated with the B1 outflow cavity. These three components present clear differences in terms of water enrichment. Finally, we confront the physical and chemical properties of the H2O emission to the predictions of current shock models.

Genome-wide cloning, identification, classification and functional analysis of cotton heat shock transcription factors in cotton (Gossypium hirsutum).

Science.gov (United States)

Wang, Jun; Sun, Na; Deng, Ting; Zhang, Lida; Zuo, Kaijing

2014-11-06

Heat shock transcriptional factors (Hsfs) play important roles in the processes of biotic and abiotic stresses as well as in plant development. Cotton (Gossypium hirsutum, 2n=4x=(AD)2=52) is an important crop for natural fiber production. Due to continuous high temperature and intermittent drought, heat stress is becoming a handicap to improve cotton yield and lint quality. Recently, the related wild diploid species Gossypium raimondii genome (2n=2x=(D5)2=26) has been fully sequenced. In order to analyze the functions of different Hsfs at the genome-wide level, detailed characterization and analysis of the Hsf gene family in G. hirsutum is indispensable. EST assembly and genome-wide analyses were applied to clone and identify heat shock transcription factor (Hsf) genes in Upland cotton (GhHsf). Forty GhHsf genes were cloned, identified and classified into three main classes (A, B and C) according to the characteristics of their domains. Analysis of gene duplications showed that GhHsfs have occurred more frequently than reported in plant genomes such as Arabidopsis and Populus. Quantitative real-time PCR (qRT-PCR) showed that all GhHsf transcripts are expressed in most cotton plant tissues including roots, stems, leaves and developing fibers, and abundantly in developing ovules. Three expression patterns were confirmed in GhHsfs when cotton plants were exposed to high temperature for 1 h. GhHsf39 exhibited the most immediate response to heat shock. Comparative analysis of Hsfs expression differences between the wild-type and fiberless mutant suggested that Hsfs are involved in fiber development. Comparative genome analysis showed that Upland cotton D-subgenome contains 40 Hsf members, and that the whole genome of Upland cotton contains more than 80 Hsf genes due to genome duplication. The expression patterns in different tissues in response to heat shock showed that GhHsfs are important for heat stress as well as fiber development. These results provide an improved

High dynamic range emission measurements of shocked energetic materials: Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX)

Science.gov (United States)

Bassett, Will P.; Dlott, Dana D.

2016-06-01

A new emission apparatus with high time resolution and high dynamic range was used to study shock-induced ignition of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine in the form of ultrafine powder (4 ± 3 μm particle size), over a range of impact velocities (0.8-4.3 km s-1) and impact durations (2.5-16 ns). A graybody model was used to extract graybody emissivities and time-dependent temperatures from a few ns to 100 μs. The emission transients consisted of three parts: a 6700 K nanosecond burst during the shocks, a 4000-4500 K temperature spike near 0.3 μs followed by a ˜3300 K tail extending out to ˜100 μs. These temperatures varied remarkably little with impact velocity and duration, while the emission intensities and emissivities changed by over an order of magnitude. The emissivity changes were interpreted with a hot spot model, where hot spot temperatures reached a maximum of 6700 K and the hot spot volume fractions increased from 5% to 100% as impact velocity increased from 1 to 3 km s-1. Changing shock durations in the 2.5-16 ns range had noticeable effects on the microsecond emission. The 0.3 μs temperature spike was much smaller or absent with 2.5 ns shocks, but prominent with longer durations. An explanation for these effects was put forth that invoked the formation of carbon-rich clusters during the shock. In this view, cluster formation was minimal with 2.5 ns shocks, but longer-duration shocks produced increasingly larger clusters, and the 0.3 μs temperature spikes represented cluster ignition.

100-Gb/s InP DP-IQ modulator for small-form-factor pluggable coherent transceivers

Science.gov (United States)

Kikuchi, Nobuhiro; Ogiso, Yoshihiro; Yamada, Eiichi

2016-02-01

We developed a compact InP-based DP-IQ modulator for small-form-factor pluggable coherent transceivers. The modulator achieves 112-Gb/s DP-QPSK modulation with a driving voltage of 6 Vppd. In addition, it provides 86-Gb/s DP-16 QAM signal generation and 240-km transmission with negligible degradation of BER performance. The halfwavelength voltage of our recent device is 1.9 V, and a high median extinction ratio of over 32 dB was achieved for more than 1,400 child MZ modulators. We have also proposed an athermal InP-based twin IQ modulator that enables us to use a modulator in a TEC-free operation. It contributes to lowering the power consumption of transceivers. Under a constant driving condition, there is little change in 56-Gb/s x 2 QPSK modulation characteristics in the range of 20 to 80°C.

Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms.

Science.gov (United States)

Amour, Julien; Brzezinska, Anna K; Jager, Zachary; Sullivan, Corbin; Weihrauch, Dorothee; Du, Jianhai; Vladic, Nikolina; Shi, Yang; Warltier, David C; Pratt, Phillip F; Kersten, Judy R

2010-03-01

Endothelial nitric oxide synthase activity is regulated by (6R-)5,6,7,8-tetrahydrobiopterin (BH4) and heat shock protein 90. The authors tested the hypothesis that hyperglycemia abolishes anesthetic preconditioning (APC) through BH4- and heat shock protein 90-dependent pathways. Myocardial infarct size was measured in rabbits in the absence or presence of APC (30 min of isoflurane), with or without hyperglycemia, and in the presence or absence of the BH4 precursor sepiapterin. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells cultured in normal (5.5 mm) or high (20 mm) glucose conditions, with or without sepiapterin (10 or 100 microm). APC decreased myocardial infarct size compared with control experiments (26 +/- 6% vs. 46 +/- 3%, respectively; P < 0.05), and this action was blocked by hyperglycemia (43 +/- 4%). Sepiapterin alone had no effect on infarct size (46 +/- 3%) but restored APC during hyperglycemia (21 +/- 3%). The beneficial actions of sepiapterin to restore APC were blocked by the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (47 +/- 2%) and the BH4 synthesis inhibitor N-acetylserotonin (46 +/- 3%). Isoflurane increased nitric oxide production to 177 +/- 13% of baseline, and this action was attenuated by high glucose concentrations (125 +/- 6%). Isoflurane increased, whereas high glucose attenuated intracellular BH4/7,8-dihydrobiopterin (BH2) (high performance liquid chromatography), heat shock protein 90-endothelial nitric oxide synthase colocalization (confocal microscopy) and endothelial nitric oxide synthase activation (immunoblotting). Sepiapterin increased BH4/BH2 and dose-dependently restored nitric oxide production during hyperglycemic conditions (149 +/- 12% and 175 +/- 9%; 10 and 100 microm, respectively). The results indicate that tetrahydrobiopterin and heat shock protein 90-regulated endothelial nitric oxide synthase activity play a central

Relative Shock Effects in Mixed Powders of Calcite, Gypsum, and Quartz: A Calibration Scheme from Shock Experiments

Science.gov (United States)

Bell, Mary S.

2009-01-01

The shock behavior of calcite and gypsum is important in understanding the Cretaceous/Tertiary event and other terrestrial impacts that contain evaporite sediments in their targets. Most interest focuses on issues of devolatilization to quantify the production of CO2 or SO2 to better understand their role in generating a temporary atmosphere and its effects on climate and biota [e.g., papers in 1,2,3,4]. Devolatilization of carbonate is also important because the dispersion and fragmentation of ejecta is strongly controlled by the expansion of large volumes of gas during the impact process as well [5,6]. Shock recovery experiments for calcite yield seemingly conflicting results: early experimental devolatilization studies [7,8,9] suggested that calcite was substantially outgassed at 30 GPa (> 50%). However, the recent petrographic work of [10,11,12] presented evidence that essentially intact calcite is recovered from 60 GPa experiments. [13] reported results of shock experiments on anhydrite, gypsum, and mixtures of those phases with silica. Their observations indicate little or no devolatilization of anhydrite shocked to 42 GPa and that the fraction of sulfur, by mass, that degassed is approx.10(exp -2) of theoretical prediction. In another (preliminary) report of shock experiments on calcite, anhydrite, and gypsum, [14] observe calcite recrystallization when shock loaded at 61 GPa, only intensive plastic deformation in anhydrite shock loaded at 63 GPa, and gypsum converted to anhydrite when shock loaded at 56 GPa. [15] shock loaded anhydrite and quartz to a peak pressure of 60 GPa. All of the quartz grains were trans-formed to glass and the platy anhydrite grains were completely pseudomorphed by small crystallized anhydrite grains. However, no evidence of interaction between the two phases could be observed and they suggest that recrystallization of anhydrite grains is the result of a solid state transformation. [16] reanalyzed the calcite and anhydrite shock

Dispersive shock waves in nonlinear and atomic optics

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Kamchatnov Anatoly

2017-01-01

Full Text Available A brief review is given of dispersive shock waves observed in nonlinear optics and dynamics of Bose-Einstein condensates. The theory of dispersive shock waves is developed on the basis of Whitham modulation theory for various situations taking place in these two fields. In particular, the full classification is established for types of wave structures evolving from initial discontinuities for propagation of long light pulses in fibers with account of steepening effect and for dynamics of the polarization mode in two-component Bose-Einstein condensates.

Barrier experiment: Shock initiation under complex loading

Energy Technology Data Exchange (ETDEWEB)

Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2016-01-12

The barrier experiments are a variant of the gap test; a detonation wave in a donor HE impacts a barrier and drives a shock wave into an acceptor HE. The question we ask is: What is the trade-off between the barrier material and threshold barrier thickness to prevent the acceptor from detonating. This can be viewed from the perspective of shock initiation of the acceptor subject to a complex pressure drive condition. Here we consider key factors which affect whether or not the acceptor undergoes a shock-to-detonation transition. These include the following: shock impedance matches for the donor detonation wave into the barrier and then the barrier shock into the acceptor, the pressure gradient behind the donor detonation wave, and the curvature of detonation front in the donor. Numerical simulations are used to illustrate how these factors affect the reaction in the acceptor.

BROAD N{sub 2}H{sup +} EMISSION TOWARD THE PROTOSTELLAR SHOCK L1157-B1

Energy Technology Data Exchange (ETDEWEB)

Codella, C.; Fontani, F.; Gómez-Ruiz, A.; Vasta, M. [INAF, Osservatorio Astrofisico di Arcetri, Largo Enrico Fermi 5, I-50125 Firenze (Italy); Viti, S. [Department of Physics and Astronomy, University College London, London (United Kingdom); Ceccarelli, C.; Lefloch, B.; Podio, L. [UJF-Grenoble 1/CNRS-INSU, Institut de Planétologie et d' Astrophysique de Grenoble (IPAG) UMR 5274, Grenoble, F-38041 (France); Benedettini, M.; Busquet, G. [INAF, Istituto di Astrofisica e Planetologia Spaziali, via Fosso del Cavaliere 100, 00133 Roma (Italy); Caselli, P., E-mail: codella@rcetri.astro.it [School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT (United Kingdom)

2013-10-10

We present the first detection of N{sub 2}H{sup +} toward a low-mass protostellar outflow, namely, the L1157-B1 shock, at ∼0.1 pc from the protostellar cocoon. The detection was obtained with the IRAM 30 m antenna. We observed emission at 93 GHz due to the J = 1-0 hyperfine lines. Analysis of this emission coupled with HIFI CHESS multiline CO observations leads to the conclusion that the observed N{sub 2}H{sup +}(1-0) line originated from the dense (≥10{sup 5} cm{sup –3}) gas associated with the large (20''-25'') cavities opened by the protostellar wind. We find an N{sub 2}H{sup +} column density of a few 10{sup 12} cm{sup –2} corresponding to an abundance of (2-8) × 10{sup –9}. The N{sub 2}H{sup +} abundance can be matched by a model of quiescent gas evolved for more than 10{sup 4} yr, i.e., for more than the shock kinematical age (≅2000 yr). Modeling of C-shocks confirms that the abundance of N{sub 2}H{sup +} is not increased by the passage of the shock. In summary, N{sub 2}H{sup +} is a fossil record of the pre-shock gas, formed when the density of the gas was around 10{sup 4} cm{sup –3}, and then further compressed and accelerated by the shock.

Spatiotemporal dynamics of underwater conical shock wave focusing

Czech Academy of Sciences Publication Activity Database

Hoffer, Petr; Lukeš, Petr; Akiyama, H.; Hosseini, H.

2017-01-01

Roč. 27, č. 4 (2017), s. 685-690 ISSN 0938-1287 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M100431203 Program:M Institutional support: RVO:61389021 Keywords : Underwater shock wave focusing * multichannel * electrohydraulic discharge * conical shock wave reflection * medical application Subject RIV: BI - Acoustics OBOR OECD: Applied mechanics Impact factor: 1.107, year: 2016 https://link.springer.com/article/10.1007/s00193-016-0703-7

From amino acids polymers, antimicrobial peptides, and histones, to their possible role in the pathogenesis of septic shock: a historical perspective

Directory of Open Access Journals (Sweden)

Ginsburg I

2017-02-01

Full Text Available Isaac Ginsburg,1 Peter Vernon van Heerden,2 Erez Koren1 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem, 2General Intensive Care Unit, Hadassah University Hospital, Jerusalem, Israel Abstract: This paper describes the evolution of our understanding of the biological role played by synthetic and natural antimicrobial cationic peptides and by the highly basic nuclear histones as modulators of infection, postinfectious sequelae, trauma, and coagulation phenomena. The authors discuss the effects of the synthetic polymers of basic poly α amino acids, poly l-lysine, and poly l-arginine on blood coagulation, fibrinolysis, bacterial killing, and blood vessels; the properties of natural and synthetic antimicrobial cationic peptides as potential replacements or adjuncts to antibiotics; polycations as opsonizing agents promoting endocytosis/phagocytosis; polycations and muramidases as activators of autolytic wall enzymes in bacteria, causing bacteriolysis and tissue damage; and polycations and nuclear histones as potential virulence factors and as markers of sepsis, septic shock, disseminated intravasclar coagulopathy, acute lung injury, pancreatitis, trauma, and other additional clinical disorders Keywords: histones, sepsis, septic shock

Miniature shock tube for laser driven shocks.

Science.gov (United States)

Busquet, Michel; Barroso, Patrice; Melse, Thierry; Bauduin, Daniel

2010-02-01

We describe in this paper the design of a miniature shock tube (smaller than 1 cm(3)) that can be placed in a vacuum vessel and allows transverse optical probing and longitudinal backside extreme ultraviolet emission spectroscopy in the 100-500 A range. Typical application is the study of laser launched radiative shocks, in the framework of what is called "laboratory astrophysics."

A study of shock mitigating materials in a split Hopkinson bar configuration. Phase 1

International Nuclear Information System (INIS)

Bateman, V.I.; Brown, F.A.; Hansen, N.R.

1998-06-01

Sandia National Laboratories (SNL) designs mechanical systems with electronics that must survive high shock environments. These mechanical systems include penetrators that must survive soil, rock, and ice penetration, nuclear transportation casks that must survive transportation environments, and laydown weapons that must survive delivery impact of 125 fps. These mechanical systems contain electronics that may operate during and after the high shock environment and that must be protected from the high shock environments. A study has been started to improve the packaging techniques for the advanced electronics utilized in these mechanical systems because current packaging techniques are inadequate for these more sensitive electronics. In many cases, it has been found that the packaging techniques currently used not only do not mitigate the shock environment but actually amplify the shock environment. An ambitious goal for this packaging study is to avoid amplification and possibly attenuate the shock environment before it reaches the electronics contained in the various mechanical systems. As part of the investigation of packaging techniques, a two phase study of shock mitigating materials is being conducted. The purpose of the first phase reported here is to examine the performance of a joint that consists of shock mitigating material sandwiched in between steel and to compare the performance of the shock mitigating materials. A split Hopkinson bar experimental configuration simulates this joint and has been used to study the shock mitigating characteristics of seventeen, unconfined materials. The nominal input for these tests is an incident compressive wave with 50 fps peak (1,500 micro var-epsilon peak) amplitude and a 100 micros duration (measured at 10% amplitude)

RNA-Seq-based analysis of cold shock response in Thermoanaerobacter tengcongensis, a bacterium harboring a single cold shock protein encoding gene.

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Bo Liu

Full Text Available BACKGROUND: Although cold shock responses and the roles of cold shock proteins in microorganisms containing multiple cold shock protein genes have been well characterized, related studies on bacteria possessing a single cold shock protein gene have not been reported. Thermoanaerobacter tengcongensis MB4, a thermophile harboring only one known cold shock protein gene (TtescpC, can survive from 50° to 80 °C, but has poor natural competence under cold shock at 50 °C. We therefore examined cold shock responses and their effect on natural competence in this bacterium. RESULTS: The transcriptomes of T. tengcongensis before and after cold shock were analyzed by RNA-seq and over 1200 differentially expressed genes were successfully identified. These genes were involved in a wide range of biological processes, including modulation of DNA replication, recombination, and repair; energy metabolism; production of cold shock protein; synthesis of branched amino acids and branched-chain fatty acids; and sporulation. RNA-seq analysis also suggested that T. tengcongensis initiates cell wall and membrane remodeling processes, flagellar assembly, and sporulation in response to low temperature. Expression profiles of TtecspC and failed attempts to produce a TtecspC knockout strain confirmed the essential role of TteCspC in the cold shock response, and also suggested a role of this protein in survival at optimum growth temperature. Repression of genes encoding ComEA and ComEC and low energy metabolism levels in cold-shocked cells are the likely basis of poor natural competence at low temperature. CONCLUSION: Our study demonstrated changes in global gene expression under cold shock and identified several candidate genes related to cold shock in T. tengcongensis. At the same time, the relationship between cold shock response and poor natural competence at low temperature was preliminarily elucidated. These findings provide a foundation for future studies on genetic

Enterococcus faecium NCIMB 10415 Modulates Epithelial Integrity, Heat Shock Protein, and Proinflammatory Cytokine Response in Intestinal Cells

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Shanti Klingspor

2015-01-01

Full Text Available Probiotics have shown positive effects on gastrointestinal diseases; they have barrier-modulating effects and change the inflammatory response towards pathogens in studies in vitro. The aim of this investigation has been to examine the response of intestinal epithelial cells to Enterococcus faecium NCIMB 10415 (E. faecium, a probiotic positively affecting diarrhea incidence in piglets, and two pathogenic Escherichia coli (E. coli strains, with specific focus on the probiotic modulation of the response to the pathogenic challenge. Porcine (IPEC-J2 and human (Caco-2 intestinal cells were incubated without bacteria (control, with E. faecium, with enteropathogenic (EPEC or enterotoxigenic E. coli (ETEC each alone or in combination with E. faecium. The ETEC strain decreased transepithelial resistance (TER and increased IL-8 mRNA and protein expression in both cell lines compared with control cells, an effect that could be prevented by pre- and coincubation with E. faecium. Similar effects were observed for the increased expression of heat shock protein 70 in Caco-2 cells. When the cells were challenged by the EPEC strain, no such pattern of changes could be observed. The reduced decrease in TER and the reduction of the proinflammatory and stress response of enterocytes following pathogenic challenge indicate the protective effect of the probiotic.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

2015-07-17

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

International Nuclear Information System (INIS)

Yang, Bin; Li, Wei; Zheng, Qichang; Qin, Tao; Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen; Liu, Sanguang; Song, Zifang

2015-01-01

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation

NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair

Energy Technology Data Exchange (ETDEWEB)

Park, Jeong-Min; Choi, Ji Ye [Department of Biological Science, Dong-A University, Busan (Korea, Republic of); Yi, Joo Mi [Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan (Korea, Republic of); Chung, Jin Woong; Leem, Sun-Hee; Koh, Sang Seok [Department of Biological Science, Dong-A University, Busan (Korea, Republic of); Kang, Tae-Hong, E-mail: thkang@dau.ac.kr [Department of Biological Science, Dong-A University, Busan (Korea, Republic of)

2015-06-05

Nucleotide excision repair (NER) is the sole mechanism of UV-induced DNA lesion repair in mammals. A single round of NER requires multiple components including seven core NER factors, xeroderma pigmentosum A–G (XPA–XPG), and many auxiliary effector proteins including ATR serine/threonine kinase. The XPA protein helps to verify DNA damage and thus plays a rate-limiting role in NER. Hence, the regulation of XPA is important for the entire NER kinetic. We found that NDR1, a novel XPA-interacting protein, modulates NER by modulating the UV-induced DNA-damage checkpoint. In quiescent cells, NDR1 localized mainly in the cytoplasm. After UV irradiation, NDR1 accumulated in the nucleus. The siRNA knockdown of NDR1 delayed the repair of UV-induced cyclobutane pyrimidine dimers in both normal cells and cancer cells. It did not, however, alter the expression levels or the chromatin association levels of the core NER factors following UV irradiation. Instead, the NDR1-depleted cells displayed reduced activity of ATR for some set of its substrates including CHK1 and p53, suggesting that NDR1 modulates NER indirectly via the ATR pathway. - Highlights: • NDR1 is a novel XPA-interacting protein. • NDR1 accumulates in the nucleus in response to UV irradiation. • NDR1 modulates NER (nucleotide excision repair) by modulating the UV-induced DNA-damage checkpoint response.

Coronal mass ejection shock fronts containing the two types of intermediate shocks

International Nuclear Information System (INIS)

Steinolfson, R.S.; Hundhausen, A.J.

1990-01-01

Numerical solutions of the time-dependent, magnetohydrodynamic (MHD) equations in two dimensions are used to demonstrate the formation of both types of intermediate shocks in a single shock front for physical conditions that are an idealization of those expected to occur in some observed coronal mass ejections. The key to producing such a shock configuration in the simulations is the use of an initial atmosphere containing a magnetic field representative of that in a coronal streamer with open field lines overlying a region of closed field lines. Previous attempts using just open field lines (perpendicular to the surface) produced shock configurations containing just one of the two intermediate shock types. A schematic of such a shock front containing both intermediate shock types has been constructed previously based solely on the known properties of MHD shocks from the Rankine-Hugoniot equations and specific requirements placed on the shock solution at points along the front where the shock normal and upstream magnetic field are aligned. The shock front also contains, at various locations along the front, a hydrodynamic (nonmagnetic) shock, a switch-on shock, and a fast shock in addition to the intermediate shocks. This particular configuration occurs when the shock front speed exceeds the upstream (preshock) intermediate wave speed but is less than a critical speed defined in the paper (equation 1) along at least some portion of the shock front. A distinctive feature of the front is that it is concave upward (away from the surface) near the region where the field in the preshock plasma is normal to the front of near the central portion of the shock front

Dynamical efficiency of collisionless magnetized shocks in relativistic jets

Science.gov (United States)

Aloy, Miguel A.; Mimica, Petar

2011-09-01

The so-called internal shock model aims to explain the light-curves and spectra produced by non-thermal processes originated in the flow of blazars and gamma-ray bursts. A long standing question is whether the tenuous collisionless shocks, driven inside a relativistic flow, are efficient enough to explain the amount of energy observed as compared with the expected kinetic power of the outflow. In this work we study the dynamic efficiency of conversion of kinetic-to-thermal/magnetic energy of internal shocks in relativistic magnetized outflows. We find that the collision between shells with a non-zero relative velocity can yield either two oppositely moving shocks (in the frame where the contact surface is at rest), or a reverse shock and a forward rarefaction. For moderately magnetized shocks (magnetization σ ~= 0.1), the dynamic efficiency in a single two-shell interaction can be as large as 40%. Hence, the dynamic efficiency of moderately magnetized shocks is larger than in the corresponding unmagnetized two-shell interaction. We find that the efficiency is only weakly dependent on the Lorentz factor of the shells and, thus internal shocks in the magnetized flow of blazars and gamma-ray bursts are approximately equally efficient.

The Whitham approach to dispersive shocks in systems with cubic–quintic nonlinearities

KAUST Repository

Crosta, M

2012-09-12

By employing a rigorous approach based on the Whitham modulation theory, we investigate dispersive shock waves arising in a high-order nonlinear Schrödinger equation with competing cubic and quintic nonlinear responses. This model finds important applications in both nonlinear optics and Bose–Einstein condensates. Our theory predicts the formation of dispersive shocks with totally controllable properties, encompassing both steering and compression effects. Numerical simulations confirm these results perfectly. Quite remarkably, shock tuning can be achieved in the regime of a very small high order, i.e. quintic, nonlinearity.

The Whitham approach to dispersive shocks in systems with cubic–quintic nonlinearities

KAUST Repository

Crosta, M; Trillo, S; Fratalocchi, Andrea

2012-01-01

By employing a rigorous approach based on the Whitham modulation theory, we investigate dispersive shock waves arising in a high-order nonlinear Schrödinger equation with competing cubic and quintic nonlinear responses. This model finds important applications in both nonlinear optics and Bose–Einstein condensates. Our theory predicts the formation of dispersive shocks with totally controllable properties, encompassing both steering and compression effects. Numerical simulations confirm these results perfectly. Quite remarkably, shock tuning can be achieved in the regime of a very small high order, i.e. quintic, nonlinearity.

Birefringence and incipient plastic deformation in elastically overdriven [100] CaF2 under shock compression

Science.gov (United States)

Li, Y.; Zhou, X. M.; Cai, Y.; Liu, C. L.; Luo, S. N.

2018-04-01

[100] CaF2 single crystals are shock-compressed via symmetric planar impact, and the flyer plate-target interface velocity histories are measured with a laser displacement interferometry. The shock loading is slightly above the Hugoniot elastic limit to investigate incipient plasticity and its kinetics, and its effects on optical properties and deformation inhomogeneity. Fringe patterns demonstrate different features in modulation of fringe amplitude, including birefringence and complicated modulations. The birefringence is attributed to local lattice rotation accompanying incipient plasticity. Spatially resolved measurements show inhomogeneity in deformation, birefringence, and fringe pattern evolutions, most likely caused by the inhomogeneity associated with lattice rotation and dislocation slip. Transiently overdriven elastic states are observed, and the incubation time for incipient plasticity decreases inversely with increasing overdrive by the elastic shock.

Dose-Related Effect of Extracorporeal Shock Wave Therapy for Plantar Fasciitis

Science.gov (United States)

Lee, Su-Jin; Kang, Jung-Ho; Kim, Ja-Young; Kim, Jin-Hong; Jung, Kwang-Ik

2013-01-01

Objective To examine the dose-related effect of extracorporeal shock wave therapy (ESWT) for plantar fasciitis. Methods Sixty patients with plantar fasciitis despite conservative treatment were enrolled. The patients were divided into a low-energy group (group L: n=30, 1,000 shocks/session, energy flux density [EFD] per shock 0.08 mJ/mm2) and a medium-energy group (group M: n=30, 1,000 shocks/session, EFD 0.16 mJ/mm2). The main outcome measures were visual analogue scale (VAS), Roles and Maudsley (RM) score, and thickness of plantar fascia (PF). To compare the effects between each group, follow-up was carried out 1 week after 3 and 6 sessions, and 1 and 3 months after ESWT. Results Significant VAS and RM score improvement, and PF thickness reduction were observed in both groups (p0.05). Conclusion Therapeutic effect might disclose a dose-related relationship; therefore, EFD and the times of the session are considerable factors when treating with ESWT. PMID:23869336

Transcriptional regulation by competing transcription factor modules.

Directory of Open Access Journals (Sweden)

Rutger Hermsen

2006-12-01

Full Text Available Gene regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by transcription factors, which control the expression of transcription units by binding to cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the design principles of these promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined input-output relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.

Energetic ion acceleration at collisionless shocks

Science.gov (United States)

Decker, R. B.; Vlahos, L.

1985-01-01

An example is presented from a test particle simulation designed to study ion acceleration at oblique turbulent shocks. For conditions appropriate at interplanetary shocks near 1 AU, it is found that a shock with theta sub B n = 60 deg is capable of producing an energy spectrum extending from 10 keV to approx. 1 MeV in approx 1 hour. In this case total energy gains result primarily from several separate episodes of shock drift acceleration, each of which occurs when particles are scattered back to the shock by magnetic fluctuations in the shock vicinity.

Energetic ion acceleration at collisionless shocks

International Nuclear Information System (INIS)

Decker, R.B.; Vlahos, L.

1985-01-01

An example is presented from a test particle simulation designed to study ion acceleration at oblique turbulent shocks. For conditions appropriate at interplanetary shocks near 1 AU, it is found that a shock with theta sub B n = 60 deg is capable of producing an energy spectrum extending from 10 keV to approx 1 MeV in approx 1 hour. In this case total energy gains result primarily from several separate episodes of shock drift acceleration, each of which occurs when particles are scattered back to the shock by magnetic fluctuations in the shock vicinity

Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China.

Science.gov (United States)

Ma, Jie; Li, Ning; Liu, Yajie; Wang, Chong; Liu, Xiaoyan; Chen, Shengmei; Xie, Xinsheng; Gan, Silin; Wang, Meng; Cao, Weijie; Wang, Fang; Liu, Yanfan; Wan, Dingming; Sun, Ling; Sun, Hui

2017-05-01

The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied. In addition, risk factors for septic shock and death were investigated. Among the 553 positive blood isolates during the study period, the prevalence of E coli was 33.3% and ESBL production strains represented 61.9% of those examined. In all the E coli strains isolated, 85.6% were multidrug-resistance (MDR), 2.4% were extensive drug resistance (XDR), and 6.0% were resistant to carbapenems. More MDR phenotype was noted in ESBL-EC strains (98.6% vs 62.8%, PE coli (94.0% and 92.0%, respectively), but lower co-resistance rates to other antibiotics. Carbapenem resistant strains retained full sensitivity to tigecycline and 60% to amikacin. Piperacillin/tazobatam was the third sensitive drug to both ESBL-EC (77.1%) and non-ESBL-EC (86.0%). In our series, 81.6% episodes received appropriate initial antibiotic treatment and no significant decrease in it was found in bacteremia due to ESBL E coli and patients with neutropenia, septic shock. Septic shock was noted in 15.5% patients and the overall 30-day mortality rate was 21.7%. Multivariate analysis revealed that induction chemotherapy (OR 2.126; 95% CI 1.624-11.332; P = .003) and polymicrobial infection (OR 3.628; 95% CI 1.065-21.219; P = .041) were risk factors for septic shock, whereas male (OR 2.223; 95% CI 1.132-12.022; P E coli bacteremia which is still a major life-threatening problem, especially for patients with septic shock. For empirical antimicrobial therapy, combination based on

Shock parameter calculations at weak interplanetary shock waves

Directory of Open Access Journals (Sweden)

J. M. Gloag

2005-02-01

Full Text Available A large set of interplanetary shock waves observed using the Ulysses spacecraft is analysed in order to determine their local parameters. For the first time a detailed analysis is extended to the thermodynamic properties of a large number of events. The intention is to relate the shock parameters to the requirements set by MHD shock theory. A uniform approach is adopted in the selection of up and downstream regions for this analysis and applied to all the shock waves. Initially, the general case of a 3 component adiabatic plasma is considered. However, the calculation of magnetosonic and Alfvénic Mach numbers and the ratio of downstream to upstream entropy produce some unexpected results. In some cases there is no clear increase in entropy across the shock and also the magnetosonic Mach number can be less than 1. It is found that a more discerning use of data along with an empirical value for the polytropic index can raise the distribution of downstream to upstream entropy ratios to a more acceptable level. However, it is also realised that many of these shocks are at the very weakest end of the spectrum and associated phenomena may also contribute to the explanation of these results.

Influence of the Vaginal Microbiota on Toxic Shock Syndrome Toxin 1 Production by Staphylococcus aureus

OpenAIRE

MacPhee, Roderick A.; Miller, Wayne L.; Gloor, Gregory B.; McCormick, John K.; Hammond, Jo-Anne; Burton, Jeremy P.; Reid, Gregor

2013-01-01

Menstrual toxic shock syndrome (TSS) is a serious illness that afflicts women of premenopausal age worldwide and arises from vaginal infection by Staphylococcus aureus and concurrent production of toxic shock syndrome toxin-1 (TSST-1). Studies have illustrated the capacity of lactobacilli to reduce S. aureus virulence, including the capacity to suppress TSST-1. We hypothesized that an aberrant microbiota characteristic of pathogenic bacteria would induce the increased production of TSST-1 and...

DNA adenine methylation modulates pathogenicity of Klebsiella pneumoniae genotype K1

Directory of Open Access Journals (Sweden)

Chi-Tai Fang

2017-08-01

Conclusion: Our results support the view that DNA adenine methylation plays an important role in modulating the pathogenicity of K. pneumoniae genotype K1. The incomplete attenuation indicates the existence of other regulatory factors.

The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.

Science.gov (United States)

Davis, Angela L; Qiao, Shuxi; Lesson, Jessica L; Rojo de la Vega, Montserrat; Park, Sophia L; Seanez, Carol M; Gokhale, Vijay; Cabello, Christopher M; Wondrak, Georg T

2015-01-16

Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinder(TM) PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin. © 2015 by The

Therapeutic Down-Modulators of Staphylococcal Superantigen-Induced Inflammation and Toxic Shock

Directory of Open Access Journals (Sweden)

Teresa Krakauer

2010-07-01

Full Text Available Staphylococcal enterotoxin B (SEB and related superantigenic toxins are potent stimulators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to toxic shock. These toxins bind directly to major histocompatibility complex (MHC class II molecules on antigen-presenting cells and specific Vb regions of T-cell receptors (TCR, resulting in hyperactivation of both monocytes/macrophages and T lymphocytes. Activated host cells produce massive amounts of proinflammatory cytokines and chemokines, activating inflammation and coagulation, causing clinical symptoms that include fever, hypotension, and shock. This review summarizes the in vitro and in vivo effects of staphylococcal superantigens, the role of pivotal mediators induced by these toxins in the pathogenic mechanisms of tissue injury, and the therapeutic agents to mitigate the toxic effects of superantigens.

Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1 and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

Directory of Open Access Journals (Sweden)

Philippe A. Melas

2018-03-01

Full Text Available Summary: Reduced eukaryotic Initiation Factor 2 (eIF2α phosphorylation (p-eIF2α enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN] reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A, the recruiter of protein phosphatase 1 (PP1. The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids. : Melas et al. show that psychoactive cannabinoids modulate levels of two eukaryotic initiation factors (eIF2α and eIF2B1 known to be involved in protein synthesis, memory formation, and drug sensitivity. Cannabinoid modulation of eIF2α in vivo is only observed in adolescent animals, and is associated with cross-sensitization to cocaine. Keywords: drug use, addiction, cannabis, marijuana, cocaine, epigenetics, eIF2a, CREB, GADD34, gateway drugs

Transforming in-situ observations of CME-driven shock accelerated protons into the shock's reference frame.

Directory of Open Access Journals (Sweden)

I. M. Robinson

2005-07-01

Full Text Available We examine the solar energetic particle event following solar activity from 14, 15 April 2001 which includes a "bump-on-the-tail" in the proton energy spectra at 0.99 AU from the Sun. We find this population was generated by a CME-driven shock which arrived at 0.99 AU around midnight 18 April. As such this population represents an excellent opportunity to study in isolation, the effects of proton acceleration by the shock. The peak energy of the bump-on-the-tail evolves to progressively lower energies as the shock approaches the observing spacecraft at the inner Lagrange point. Focusing on the evolution of this peak energy we demonstrate a technique which transforms these in-situ spectral observations into a frame of reference co-moving with the shock whilst making allowance for the effects of pitch angle scattering and focusing. The results of this transform suggest the bump-on-the-tail population was not driven by the 15 April activity but was generated or at least modulated by a CME-driven shock which left the Sun on 14 April. The existence of a bump-on-the-tail population is predicted by models in Rice et al. (2003 and Li et al. (2003 which we compare with observations and the results of our analysis in the context of both the 14 April and 15 April CMEs. We find an origin of the bump-on-the-tail at the 14 April CME-driven shock provides better agreement with these modelled predictions although some discrepancy exists as to the shock's ability to accelerate 100 MeV protons.

Keywords. Solar physics, astrophysics and astronomy (Energetic particles; Flares and mass ejections – Space plasma physics (Transport processes

An investigation of the structure of plasma produced by reflected shock waves

International Nuclear Information System (INIS)

Phillips, M.G.R.; Pugatschew, A.A.

1979-05-01

Space and time resolved measurements of electron density and temperature have been made in the reflected-shock plasma produced by a Mach 20 incident shock wave propagating in argon at an initial pressure of 1.5 Torr. The peak electron density was found to decrease away from the reflecting wall in such a way that the plasma was fairly uniform at all times. Close to the reflecting wall (0.2 cm away) the measured peak electron density was close to (i.e. about 20% lower than) the predicted equilibrium value but further away (1.0 cm) it was lower by a factor 4. Possible reasons for this discrepancy are discussed. Calculations of reflected-shock plasma structure based on incident shock structure are only partially supported by available experimental evidence

DESTRUCTION OF INTERSTELLAR DUST IN EVOLVING SUPERNOVA REMNANT SHOCK WAVES

International Nuclear Information System (INIS)

Slavin, Jonathan D.; Dwek, Eli; Jones, Anthony P.

2015-01-01

Supernova generated shock waves are responsible for most of the destruction of dust grains in the interstellar medium (ISM). Calculations of the dust destruction timescale have so far been carried out using plane parallel steady shocks, however, that approximation breaks down when the destruction timescale becomes longer than that for the evolution of the supernova remnant (SNR) shock. In this paper we present new calculations of grain destruction in evolving, radiative SNRs. To facilitate comparison with the previous study by Jones et al., we adopt the same dust properties as in that paper. We find that the efficiencies of grain destruction are most divergent from those for a steady shock when the thermal history of a shocked gas parcel in the SNR differs significantly from that behind a steady shock. This occurs in shocks with velocities ≳200 km s −1 for which the remnant is just beginning to go radiative. Assuming SNRs evolve in a warm phase dominated ISM, we find dust destruction timescales are increased by a factor of ∼2 compared to those of Jones et al., who assumed a hot gas dominated ISM. Recent estimates of supernova rates and ISM mass lead to another factor of ∼3 increase in the destruction timescales, resulting in a silicate grain destruction timescale of ∼2–3 Gyr. These increases, while not able to resolve the problem of the discrepant timescales for silicate grain destruction and creation, are an important step toward understanding the origin and evolution of dust in the ISM

Shock capturing techniques for hphp-adaptive finite elements

Czech Academy of Sciences Publication Activity Database

Hierro, A.; Kůs, Pavel; Badia, S.

2016-01-01

Roč. 309, 1 September (2016), s. 532-553 ISSN 0045-7825 Institutional support: RVO:67985840 Keywords : hphp-adaptivity * discontinuous Galerkin * shock capturing Subject RIV: BA - General Mathematics Impact factor: 3.949, year: 2016 http://www.sciencedirect.com/science/article/pii/S0045782516305862

Shock physics with the nova laser for ICF applications. Revision 1

International Nuclear Information System (INIS)

Hammel, B.A.; Cauble, R.; Celliers, P.

1995-01-01

The physics of high pressure shocks plays a central role in Inertial Confinement Fusion (ICF). In indirect drive ICF, x-rays from a gold cavity (hohlraum) are used to ablatively drive a series of high pressure shocks into a spherical target (capsule). These shocks converge at the center, compressing the fuel and forming a hot dense core. The target performance, such as peak fuel density and temperature and neutron yield, depends critically on hock timing, and material compressibility. Accurate predictions of NIF target performance depends critically on shock timing and material compressibility. Current measurement techniques enable us to accurately determine shock timing in planar samples of abator material as a function of laser drive. Although this technique does not separately address uncertainties in material EOS and opacity, it does allow us to tune the laser drive until the desired shock timing is achieved. Experiments to directly address the EOS of D 2 ice are planned to further increase the margin for ignition in current target designs

The number of prehospital defibrillation shocks and 1-month survival in patients with out-of-hospital cardiac arrest.

Science.gov (United States)

Hasegawa, Manabu; Abe, Takeru; Nagata, Takashi; Onozuka, Daisuke; Hagihara, Akihito

2015-04-17

The relationship between the number of pre-hospital defibrillation shocks and treatment outcome in patients with out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF) is unknown currently. We examined the association between the number of pre-hospitalization defibrillation shocks and 1-month survival in OHCA patients. We conducted a prospective observational study using national registry data obtained from patients with OHCA between January 1, 2009 and December 31, 2012 in Japan. The study subjects were ≥ 18-110 years of age, had suffered from an OHCA before arrival of EMS personnel, had a witnessed collapse, had an initial rhythm that was shockable [VF/ventricular tachycardia (pulseless VT)], were not delivered a shock using a public automated external defibrillator (AED), received one or more shocks using a biphasic defibrillator by EMS personnel, and were transported to a medical institution between January 1, 2009 and December 31, 2012. There were 20,851 OHCA cases which met the inclusion criteria during the study period. Signal detection analysis was used to identify the cutoff point in the number of prehospital defibrillation shocks most closely related to one-month survival. Variables related to the number of defibrillations or one-month survival in OHCA were identified using multiple logistic regression analysis. A cutoff point in the number of pre-hospital defibrillation shocks most closely associated with 1-month OHCA survival was between two and three (χ(2) = 209.61, p < 0.0001). Among those patients who received two shocks or less, 34.48% survived for at least 1 month, compared with 24.75% of those who received three shocks or more. The number of defibrillations (odds ratio [OR] = 1.19, 95% CI: 1.03, 1.38), OHCA origin (OR = 2.81, 95% CI: 2.26, 3.49), use of ALS devices (OR = 0.68, 95% CI: 0.59, 0.79), use of epinephrine (OR = 0.33, 95% C: 0.28, 0.39), interval between first defibrillation and first ROSC (OR = 1.45, 95

Numerical analysis of three-dimensional MHD shock interactions in an inhomogeneous medium

International Nuclear Information System (INIS)

Prndergast, M.; Wu, S.T.

1987-01-01

Study of the formation and propagation of solar-originated shock waves in heliospheric space has attracted significant attention in the past decade. This attention is important because the propagation of shocks in heliospheric space has been thought of as one of the major physical processes for solar wind and cosmic ray modulations and their subsequent influence on the earth's environment. A version of the two step Lax-Wendroff difference method is used to seek solutions of the unsteady magnetohydrodynamic (MHD) equations for the study of a solar flare generated shock wave propagating through an inhomogeneous medium. 8 references

Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

Science.gov (United States)

Lecomte, Marie-José; Bertolus, Chloé; Ramanantsoa, Nélina; Saurini, Françoise; Callebert, Jacques; Sénamaud-Beaufort, Catherine; Ringot, Maud; Bourgeois, Thomas; Matrot, Boris; Collet, Corinne; Nardelli, Jeannette; Mallet, Jacques; Vodjdani, Guilan; Gallego, Jorge; Launay, Jean-Marie; Berrard, Sylvie

2018-04-01

Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.

Elastic-plastic fracture mechanics study of thermal shock cracking

International Nuclear Information System (INIS)

Hirano, K.; Kobayashi, H.; Nakazawa, H.

1980-01-01

This paper describes thermal shock experiments conducted on a nuclear pressure vessel steel (A533 Grade B Class 1), an AISI304 steel and a tool steel (JIS SKD62) using both a new thermal shock test facility and method. Analysis of their quasi-static thermal stress intensity factors is performed on the basis of linear-elastic fracture mechanics; and a thermal shock fracture toughness value, Ksub(tsc) is evaluated. Then elastic-plastic fracture toughness tests are carried out in the same high temperature range of the thermal shock experiment, and a relation between the stretched zone width, SZW, formed as a result of the fatigue precrack tip plastic blunting and the J-integral is clarified. An elastic-plastic thermal shock fracture toughness value, Jsub(tsc), is evaluated from a critical value of the stretched zone width, SZWsub(tsc), at the initiation of the thermal shock cracking by using the relation between SZW and J. The Jsub(tsc) value is compared with an elastic-plastic fracture toughness value, Jsub(Ic), and the difference between these Jsub(tsc) and Jsub(Ic) values is discussed on the basis of fractography. (author)

Experimental investigation of shock wave - bubble interaction

Energy Technology Data Exchange (ETDEWEB)

Alizadeh, Mohsen

2010-04-09

In this work, the dynamics of laser-generated single cavitation bubbles exposed to lithotripter shock waves has been investigated experimentally. The energy of the impinging shock wave is varied in several steps. High-speed photography and pressure field measurements simultaneously with image acquisition provide the possibility of capturing the fast bubble dynamics under the effect of the shock wave impact. The pressure measurement is performed using a fiber optic probe hydrophone (FOPH) which operates based on optical diagnostics of the shock wave propagating medium. After a short introduction in chapter 1 an overview of the previous studies in chapter 2 is presented. The reported literatures include theoretical and experimental investigations of several configurations of physical problems in the field of bubble dynamics. In chapter 3 a theoretical description of propagation of a shock wave in a liquid like water has been discussed. Different kinds of reflection of a shock wave at an interface are taken into account. Undisturbed bubble dynamics as well as interaction between a planar shock wave and an initially spherical bubble are explored theoretically. Some physical parameters which are important in this issue such as the velocity of the shock-induced liquid jet, Kelvin impulse and kinetic energy are explained. The shock waves are generated in a water filled container by a focusing piezoelectric generator. The shock wave profile has a positive part with pulse duration of ∼1 μs followed by a longer tension tail (i.e. ∼3 μs). In chapter 4 high-speed images depict the propagation of a shock wave in the water filled tank. The maximum pressure is also derived for different intensity levels of the shock wave generator. The measurement is performed in the free field (i.e. in the absence of laser-generated single bubbles). In chapter 5 the interaction between lithotripter shock waves and laserinduced single cavitation bubbles is investigated experimentally. An

Multiple spacecraft observations of interplanetary shocks Four spacecraft determination of shock normals

Science.gov (United States)

Russell, C. T.; Mellott, M. M.; Smith, E. J.; King, J. H.

1983-01-01

ISEE 1, 2, 3, IMP 8, and Prognoz 7 observations of interplanetary shocks in 1978 and 1979 provide five instances where a single shock is observed by four spacecraft. These observations are used to determine best-fit normals for these five shocks. In addition to providing well-documented shocks for future investigations these data allow the evaluation of the accuracy of several shock normal determination techniques. When the angle between upstream and downstream magnetic field is greater than 20 deg, magnetic coplanarity can be an accurate single spacecraft method. However, no technique based solely on the magnetic measurements at one or multiple sites was universally accurate. Thus, the use of overdetermined shock normal solutions, utilizing plasma measurements, separation vectors, and time delays together with magnetic constraints, is recommended whenever possible.

Mesenteric lymph reperfusion exacerbates spleen injury caused by superior mesenteric artery occlusion shock

Energy Technology Data Exchange (ETDEWEB)

Li, L.L.; Zhang, C.H.; Liu, J.C.; Yang, L.N.; Niu, C.Y.; Zhao, Z.G. [Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei, China, Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei (China)

2014-04-15

The intestinal lymph pathway plays an important role in the pathogenesis of organ injury following superior mesenteric artery occlusion (SMAO) shock. We hypothesized that mesenteric lymph reperfusion (MLR) is a major cause of spleen injury after SMAO shock. To test this hypothesis, SMAO shock was induced in Wistar rats by clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h. Similarly, MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h, followed by reperfusion for 2 h. In the MLR+SMAO group rats, both the SMA and MLD were clamped and then released for reperfusion for 2 h. SMAO shock alone elicited: 1) splenic structure injury, 2) increased levels of malondialdehyde, nitric oxide (NO), intercellular adhesion molecule-1, endotoxin, lipopolysaccharide receptor (CD14), lipopolysaccharide-binding protein, and tumor necrosis factor-α, 3) enhanced activities of NO synthase and myeloperoxidase, and 4) decreased activities of superoxide dismutase and ATPase. MLR following SMAO shock further aggravated these deleterious effects. We conclude that MLR exacerbates spleen injury caused by SMAO shock, which itself is associated with oxidative stress, excessive release of NO, recruitment of polymorphonuclear neutrophils, endotoxin translocation, and enhanced inflammatory responses.

Radiosensitization of normoxic and hypoxic h1339 lung tumor cells by heat shock protein 90 inhibition is independent of hypoxia inducible factor-1α.

Science.gov (United States)

Schilling, Daniela; Bayer, Christine; Li, Wei; Molls, Michael; Vaupel, Peter; Multhoff, Gabriele

2012-01-01

Ionizing irradiation is a commonly accepted treatment modality for lung cancer patients. However, the clinical outcome is hampered by normal tissue toxicity and tumor hypoxia. Since tumors often have higher levels of active heat shock protein 90 (Hsp90) than normal tissues, targeting of Hsp90 might provide a promising strategy to sensitize tumors towards irradiation. Hsp90 client proteins include oncogenic signaling proteins, cell cycle activators, growth factor receptors and hypoxia inducible factor-1α (HIF-1α). Overexpression of HIF-1α is assumed to promote malignant transformation and tumor progression and thus might reduce the accessibility to radiotherapy. Herein, we describe the effects of the novel Hsp90 inhibitor NVP-AUY922 and 17-allylamino-17-demethoxygeldanamycin (17-AAG), as a control, on HIF-1α levels and radiosensitivity of lung carcinoma cells under normoxic and hypoxic conditions. NVP-AUY922 exhibited a similar biological activity to that of 17-AAG, but at only 1/10 of the dose. As expected, both inhibitors reduced basal and hypoxia-induced HIF-1α levels in EPLC-272H lung carcinoma cells. However, despite a down-regulation of HIF-1α upon Hsp90 inhibition, sensitivity towards irradiation remained unaltered in EPLC-272H cells under normoxic and hypoxic conditions. In contrast, treatment of H1339 lung carcinoma cells with NVP-AUY922 and 17-AAG resulted in a significant up-regulation of their initially high HIF-1α levels and a concomitant increase in radiosensitivity. In summary, our data show a HIF-1α-independent radiosensitization of normoxic and hypoxic H1339 lung cancer cells by Hsp90 inhibition.

First order and second order fermi acceleration of energetic charged particles by shock waves

International Nuclear Information System (INIS)

Webb, G.M.

1983-01-01

Steady state solutions of the cosmic ray transport equation describing first order Fermi acceleration of energetic charged particles at a plane shock (without losses) and second order Fermi acceleration in the downstream region of the shock are derived. The solutions for the isotropic part of the phase space distribution function are expressible as eigenfunction expansions, being superpositions of series of power law momentum spectra, with the power law indices being the roots of an eigenvalue equation. The above exact analytic solutions are for the case where the spatial diffusion coefficient kappa is independent of momentum. The solutions in general depend on the shock compression ratio, the modulation parameters V 1 L/kappa 1 , V 2 L/kappa 2 (V is the plasma velocity, kappa is the energetic particle diffusion coefficient, and L a characteristic length over which second order Fermi acceleration is effective) in the upstream and downstream regions of the shock, respectively, and also on a further dimensionless parameter, zeta, characterizing second order Fermi acceleration. In the limit as zeta→0 (no second order Fermi acceleration) the power law momentum spectrum characteristic of first order Fermi acceleration (depending only on the shock compression ratio) obtained previously is recovered. Perturbation solutions for the case where second order Fermi effects are small, and for realistic diffusion coefficients (kappainfinityp/sup a/, a>0, p = particle momentum), applicable at high momenta, are also obtained

Modeling Shocks Detected by Voyager 1 in the Local Interstellar Medium

Energy Technology Data Exchange (ETDEWEB)

Kim, T. K.; Pogorelov, N. V. [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, Huntsville, AL 35805 (United States); Burlaga, L. F. [NASA Goddard Space Flight Center, Code 673, Greenbelt, MD 20771 (United States)

2017-07-10

The magnetometer (MAG) on Voyager 1 ( V1 ) has been sampling the interstellar magnetic field (ISMF) since 2012 August. The V1 MAG observations have shown draped ISMF in the very local interstellar medium disturbed occasionally by significant enhancements in magnetic field strength. Using a three-dimensional, data-driven, multi-fluid model, we investigated these magnetic field enhancements beyond the heliopause that are supposedly associated with solar transients. To introduce time-dependent effects at the inner boundary at 1 au, we used daily averages of the solar wind parameters from the OMNI data set. The model ISMF strength, direction, and proton number density are compared with V1 data beyond the heliopause. The model reproduced the large-scale fluctuations between 2012.652 and 2016.652, including major events around 2012.9 and 2014.6. The model also predicts shocks arriving at V1 around 2017.395 and 2019.502. Another model driven by OMNI data with interplanetary coronal mass ejections (ICMEs) removed at the inner boundary suggests that ICMEs may play a significant role in the propagation of shocks into the interstellar medium.

Heat shock protein 90-sheltered overexpression of insulin-like growth factor 1 receptor contributes to malignancy of thymic epithelial tumors.

Science.gov (United States)

Breinig, Marco; Mayer, Philipp; Harjung, Andreas; Goeppert, Benjamin; Malz, Mona; Penzel, Roland; Neumann, Olaf; Hartmann, Arndt; Dienemann, Hendrik; Giaccone, Giuseppe; Schirmacher, Peter; Kern, Michael André; Chiosis, Gabriela; Rieker, Ralf Joachim

2011-04-15

The underlying molecular mechanisms of thymic epithelial malignancies (TEMs) are poorly understood. Consequently, there is a lack of efficacious targeted therapies and patient prognosis remains dismal, particularly for advanced TEMs. We sought to investigate protumorigenic mechanism relevant to this understudied cancer. Recently established cell lines derived from thymic epithelial tumors were used as a model system. The antitumor activity of specific heat shock protein 90 (Hsp90) inhibitors was investigated by an analysis of cell viability, cell cycle, and apoptosis using MTT-assays and flow cytometry. Western blotting was used to investigate the altered expression of Hsp90 clients. Pharmacological inhibitors against select Hsp90 clients, as well as RNAi, were employed to test the relevance of each client independently. Tissue microarray analysis was performed to match the in vitro findings with observations obtained from patient-derived samples. Hsp90 inhibition significantly reduces cell viability of thymic carcinoma cells, induces cell cycle arrest and apoptosis, and blocks invasiveness. Hsp90 inhibition triggers the degradation of multiple oncogenic clients, for example insulin-like growth factor 1 receptor (IGF-1R), CDK4, and the inactivation of PI3K/Akt and RAF/Erk signaling. Mechanistically, the IGF/IGF-1R-signaling axis contributes to the establishment of the antiapoptotic phenotype of thymic cancer cells. Finally, IGF-1R is overexpressed in advanced TEMs. We have unraveled a novel protumorigenic mechanism in TEMs, namely Hsp90-capacitated overexpression of IGF-1R, which confers apoptosis evasion in malignant thymic epithelial cells. Our data indicate that Hsp90 inhibition, which simultaneously blocks multiple cancer hallmarks, represents a therapeutic strategy in TEMs that may merit evaluation in clinical trials. ©2011 AACR.

Modification of embryonic resistance to heat shock in cattle by melatonin and genetic variation in HSPA1L.

Science.gov (United States)

Ortega, M Sofia; Rocha-Frigoni, Nathália A S; Mingoti, Gisele Zoccal; Roth, Zvi; Hansen, Peter J

2016-11-01

The objectives were to test whether (1) melatonin blocks inhibition of embryonic development caused by heat shock at the zygote stage, and (2) the frequency of a thermoprotective allele for HSPA1L is increased in blastocysts formed from heat-shocked zygotes as compared with blastocysts from control zygotes. It was hypothesized that melatonin prevents effects of heat shock on development by reducing accumulation of reactive oxygen species (ROS) and that embryos inheriting the thermoprotective allele of HSPA1L would be more likely to survive heat shock. Effects of 1 µM melatonin on ROS were determined in experiments 1 and 2. Zygotes were cultured at 38.5 or 40°C for 3 h in the presence of CellROX reagent (ThermoFisher Scientific, Waltham, MA). Culture was in a low [5% (vol/vol)] oxygen (experiment 1) or low or high [21% (vol/vol)] oxygen environment (experiment 2). Heat shock and high oxygen increased ROS; melatonin decreased ROS. Development was assessed in experiments 3 and 4. In experiment 3, zygotes were cultured in low oxygen ± 1 µM melatonin and exposed to 38.5 or 40°C for 12 h (experiment 1) beginning 8 h after fertilization. Melatonin did not protect the embryo from heat shock. Experiment 4 was performed similarly except that temperature treatments (38.5 or 40°C, 24 h) were performed in a low or high oxygen environment (2×2 × 2 factorial design with temperature, melatonin, and oxygen concentration as main effects), and blastocysts were genotyped for a deletion (D) mutation (C→D) in the promoter region of HSPA1L associated with thermotolerance. Heat shock decreased percent of zygotes developing to the blastocyst stage independent of melatonin or oxygen concentration. Frequency of genotypes for HSPA1L was affected by oxygen concentration and temperature, with an increase in the D allele for blastocysts that developed in high oxygen and following heat shock. It was concluded that (1) lack of effect of melatonin or oxygen concentration on embryonic

Multiple spacecraft observations of interplanetary shocks: four spacecraft determination of shock normals

International Nuclear Information System (INIS)

Russell, C.T.; Mellott, M.M.; Smith, E.J.; King, J.H.

1983-01-01

ISEE 1,2,3 IMP8, and Prognoz 7 observations of interplanetary shocks in 1978 and 1979 provide five instances where a single shock is observed by four spacecraft. These observations are used to determine best-fit normals for these five shocks. In addition to providing well-documented shocks for furture techniques. When the angle between upstream and downstream magnetic field is greater than 20, magnetic coplanarity can be an accurate single spacecraft method. However, no technique based solely on the magnetic measurements at one or multiple sites was universally accurate. Thus, we recommend using overdetermined shock normal solutions whenever possible, utilizing plasma measurements, separation vectors, and time delays together with magnetic constraints

Simple, economical heat-shock devices for zebrafish housing racks.

Science.gov (United States)

Duszynski, Robert J; Topczewski, Jacek; LeClair, Elizabeth E

2011-12-01

One reason for the popularity of the zebrafish (Danio rerio) as a model vertebrate is the ability to manipulate gene expression in this organism. A common method is to induce gene expression transiently under control of a heat-shock promoter (e.g., hsp70l). By making simple mechanical adjustments to small aquarium heaters (25-50W), we were able to produce consistent and reliable heat-shock conditions within a conventional zebrafish housing system. Up to two heat-shock intervals per day (>37°C) could be maintained under conditions of continuous flow (5-25 mL/min). Temperature logging every 30 s indicated rapid warm up times, consistent heat-shock lengths, and accurate and precise peak water temperatures (mean±SD=38°C±0.2°C). The biological effects of these heat-shock treatments were confirmed by observing inducible expression of enhanced green fluorescent protein (EGFP) and inhibition of caudal fin regeneration in a transgenic fish line expressing a dominant negative fibroblast growth factor receptor (Tg(hsp70l:dnfgfr1-EGFP)(pd1)). These devices are inexpensive, easily modified, and can be calibrated to accommodate a variety of experimental designs. After setup on a programmable timer, the heaters require no intervention to produce consistent daily heat shocks, and all other standard care protocols can be followed in the fish facility. The simplicity and stability of these devices make them suitable for long-term heat shocks at any stage of the zebrafish lifecycle (>7 days postfertilization), and useful for both laboratory and classroom experiments on transgenic zebrafish.

The Dynamic Quasiperpendicular Shock: Cluster Discoveries

Czech Academy of Sciences Publication Activity Database

Krasnoselskikh, V.; Balikhin, M.; Walker, S. N.; Schwartz, S.; Sundkvist, D.; Lobzin, V.; Gedalin, M.; Bale, S. D.; Mozer, F.; Souček, Jan; Hobara, Y.; Comisel, H.

2013-01-01

Roč. 178, 2-4 (2013), s. 535-598 ISSN 0038-6308 Institutional support: RVO:68378289 Keywords : collisionless shocks * waves in plasmas * nonstationarity * shock scales * plasma heating and acceleration * wave-particle interactions Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 5.874, year: 2013 http://link.springer.com/article/10.1007%2Fs11214-013-9972-y

Behaviors and housing inertia are key factors in determining the consequences of a shock in transportation costs

International Nuclear Information System (INIS)

Gusdorf, Francois; Hallegatte, Stephane

2007-01-01

This paper investigates the consequences of a sudden increase in transportation costs when household behaviors and building inertia are accounted for. A theoretical framework is proposed, capturing the interactions between behaviors, transportation costs and urban structure. Numerical simulations show that changes in households and landowners' choices reduce significantly the long-term adverse effects of a shock in transportation costs. Indeed, the shock translates, over the long run, into a more concentrated housing that limits households utility losses and maintains landowners' income. But, because of building inertia, the shock leads first to a long transition, during which the adjustment is constrained by a suboptimal housing-supply structure. Then, households support larger losses than in the final stage, though lower than with no behavior adjustment, and landowners experience a large decrease in their aggregate income and an important redistribution of wealth. Thus, behaviors and building inertia are key factors in determining the vulnerability to transportation price variability and to the introduction of climate policies. Our policy conclusions are that: (i) if a long-term increase in transportation costs is unavoidable because of climate change or resource scarcity, a smooth change prevents to some extent the negative transition effects and (ii) fast-growing cities of the developing world can reduce their future vulnerability to shocks in transportation costs through the implementation of policies that limit urban sprawl

Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock

Energy Technology Data Exchange (ETDEWEB)

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhang, Hailin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Wang, Xiumei; Wang, Yu; He, Zehong; Yao, Huan

2016-08-15

LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10 mg/kg) or DEX (5 mg/kg) at 1 and 12 h before injecting LPS (30 mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72 h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway. - Highlights: • Cavidine significantly reduced mortality in mice during 72 h after LPS injection. • Cavidine attenuated histopathological changes in lung, liver and kidney. • Cavidine decreased the level of early inflammatory cytokine TNF-α, IL-6 in LPS- stimulated mice. • Cavidine inhibited late inflammatory cytokine HMGB1 through MAPK pathway.

Converging shocks in elastic-plastic solids.

Science.gov (United States)

Ortega, A López; Lombardini, M; Hill, D J

2011-11-01

We present an approximate description of the behavior of an elastic-plastic material processed by a cylindrically or spherically symmetric converging shock, following Whitham's shock dynamics theory. Originally applied with success to various gas dynamics problems, this theory is presently derived for solid media, in both elastic and plastic regimes. The exact solutions of the shock dynamics equations obtained reproduce well the results obtained by high-resolution numerical simulations. The examined constitutive laws share a compressible neo-Hookean structure for the internal energy e=e(s)(I(1))+e(h)(ρ,ς), where e(s) accounts for shear through the first invariant of the Cauchy-Green tensor, and e(h) represents the hydrostatic contribution as a function of the density ρ and entropy ς. In the strong-shock limit, reached as the shock approaches the axis or origin r=0, we show that compression effects are dominant over shear deformations. For an isothermal constitutive law, i.e., e(h)=e(h)(ρ), with a power-law dependence e(h) is proportional to ρ(α), shock dynamics predicts that for a converging shock located at r=R(t) at time t, the Mach number increases as M is proportional to [log(1/R)](α), independently of the space index s, where s=2 in cylindrical geometry and 3 in spherical geometry. An alternative isothermal constitutive law with p(ρ) of the arctanh type, which enforces a finite density in the strong-shock limit, leads to M is proportional to R(-(s-1)) for strong shocks. A nonisothermal constitutive law, whose hydrostatic part e(h) is that of an ideal gas, is also tested, recovering the strong-shock limit M is proportional to R(-(s-1)/n(γ)) originally derived by Whitham for perfect gases, where γ is inherently related to the maximum compression ratio that the material can reach, (γ+1)/(γ-1). From these strong-shock limits, we also estimate analytically the density, radial velocity, pressure, and sound speed immediately behind the shock. While the

A polar-drive shock-ignition design for the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Anderson, K. S.; McKenty, P. W.; Collins, T. J. B.; Craxton, R. S.; Delettrez, J. A.; Marozas, J. A.; Skupsky, S.; Shvydky, A. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Betti, R. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Fusion Science Center, University of Rochester, Rochester, New York 14623 (United States); Departments of Mechanical Engineering and Physics, University of Rochester, Rochester, New York 14627 (United States); Hohenberger, M.; Theobald, W.; Lafon, M.; Nora, R. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623 (United States); Fusion Science Center, University of Rochester, Rochester, New York 14623 (United States)

2013-05-15

Shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)] is being pursued as a viable option to achieve ignition on the National Ignition Facility (NIF). Shock-ignition target designs use a high-intensity laser spike at the end of a low-adiabat assembly pulse to launch a spherically convergent strong shock to ignite the hot spot of an imploding capsule. A shock-ignition target design for the NIF is presented. One-dimensional simulations indicate an ignition threshold factor of 4.1 with a gain of 58. A polar-drive beam-pointing configuration for shock-ignition experiments on the NIF at 750 kJ is proposed. The capsule design is shown to be robust to the various one- and two-dimensional effects and nonuniformities anticipated on the NIF. The target is predicted to ignite with a gain of 38 when including all anticipated levels of nonuniformity and system uncertainty.

First detection of multi-shocks in RR Lyrae stars from Antarctica : A possible explanation of the Blazhko effect

International Nuclear Information System (INIS)

Chadid, M.; Vernin, J.; Zalian, C.; Pouzenc, C.; Abe, L.; Agabi, A.; Aristidi, E.; Mékarnia, D.; Preston, G.; Liu, L.Y.; Trinquet, H.

2014-01-01

We present the first detection of multi-shocks propagating through the atmosphere of the Blazhko star S Arae using uninterrupted, accurate optical photometric data collected during one polar night, 150 days from Antarctica at Dome C, with the Photometer AntarctIca eXtinction (PAIX). We acquired 89,736 CCD frames during 323 pulsation cycles and 3 Blazhko cycles. We detected two new light curve properties in the PAIX light curve, jump and rump, which we associated with two new post-maximum shock waves Sh PM1 and Sh PM2 . jump, lump, rump, bump, and hump are induced by five shock waves, with different amplitudes and origins, Sh PM1 , Sh PM , Sh PM2 , Sh PM3 , and the main shock Sh H+He . Correlations between the length of rise time and light amplitude and Sh PM3 are monotonous during three Blazhko cycles, but the pulsation curve is double peaked. We discuss the physical mechanisms driving the modulation of these quantities. Finally, we hypothesize that the origin of the Blazhko effect is a dynamical interaction between a multi-shock structure and an outflowing wind in a coronal structure.

First detection of multi-shocks in RR Lyrae stars from Antarctica : A possible explanation of the Blazhko effect

Energy Technology Data Exchange (ETDEWEB)

Chadid, M.; Vernin, J.; Zalian, C.; Pouzenc, C.; Abe, L.; Agabi, A.; Aristidi, E.; Mékarnia, D. [Université Nice Sophia-Antipolis, Observatoire de la Côte d' Azur, UMR 7293, Parc Valrose, F-06108 Nice Cedex 02 (France); Preston, G. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Liu, L.Y. [National Astronomical Observatories, Chinese Academy of Sciences, 20A Datun Road, Chaoyang District, Beijing (China); Trinquet, H., E-mail: chadid@unice.fr [DGA Matrise de l' Information, BP 7, F-35998 Rennes Armees (France)

2014-11-01

We present the first detection of multi-shocks propagating through the atmosphere of the Blazhko star S Arae using uninterrupted, accurate optical photometric data collected during one polar night, 150 days from Antarctica at Dome C, with the Photometer AntarctIca eXtinction (PAIX). We acquired 89,736 CCD frames during 323 pulsation cycles and 3 Blazhko cycles. We detected two new light curve properties in the PAIX light curve, jump and rump, which we associated with two new post-maximum shock waves Sh{sub PM1} and Sh{sub PM2}. jump, lump, rump, bump, and hump are induced by five shock waves, with different amplitudes and origins, Sh{sub PM1}, Sh{sub PM}, Sh{sub PM2}, Sh{sub PM3}, and the main shock Sh{sub H+He}. Correlations between the length of rise time and light amplitude and Sh{sub PM3} are monotonous during three Blazhko cycles, but the pulsation curve is double peaked. We discuss the physical mechanisms driving the modulation of these quantities. Finally, we hypothesize that the origin of the Blazhko effect is a dynamical interaction between a multi-shock structure and an outflowing wind in a coronal structure.

An Analysis of an Implicit Factored Scheme for Simulating Shock Waves

Science.gov (United States)

1988-05-01

can cope with a wide range of boundary conditions and equations of state, For modelling -( shock waves in solids, elastic- plastic terms must also be...positive caracteristic speeds. One-sided schemes have superior dissipative and dispersive properties compared to those of centered schemes (Steger and...Elastic- plastic con. ditions must be- incorporated into the problem and usually the addition of suitable bource or sink terms to c-’ustion (1

Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG and is associated with increased 30-day mortality in septic shock.

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Simon T Schäfer

Full Text Available BACKGROUND: Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1 NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS in monocytes in vitro, and 2 mortality in septic shock. METHODS: Monocytes of volunteers with the homozygous insertion (II; n = 5 or deletion (DD; n = 6 NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M, and NF-κB1 nuclear translocation was assessed (immunofluorescence. Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. RESULTS: Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001 but not in DD genotypes (51%±15;p = n.s.. Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD receiving hydrocortisone had a much greater 30-day-mortality (57.6% than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001. In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. CONCLUSION: Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele

Hydrocortisone Fails to Abolish NF-κB1 Protein Nuclear Translocation in Deletion Allele Carriers of the NFKB1 Promoter Polymorphism (-94ins/delATTG) and Is Associated with Increased 30-Day Mortality in Septic Shock

Science.gov (United States)

Schäfer, Simon T.; Gessner, Sophia; Scherag, André; Rump, Katharina; Frey, Ulrich H.; Siffert, Winfried; Westendorf, Astrid M.; Steinmann, Jörg; Peters, Jürgen; Adamzik, Michael

2014-01-01

Background Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Methods Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Results Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Conclusion Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the

Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1.

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Svensson, Katrin J; Christianson, Helena C; Wittrup, Anders; Bourseau-Guilmain, Erika; Lindqvist, Eva; Svensson, Lena M; Mörgelin, Matthias; Belting, Mattias

2013-06-14

The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signaling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signaling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft-associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signaling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signaling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.

Geometrical shock dynamics for magnetohydrodynamic fast shocks

KAUST Repository

Mostert, W.; Pullin, D. I.; Samtaney, Ravi; Wheatley, V.

2016-01-01

We describe a formulation of two-dimensional geometrical shock dynamics (GSD) suitable for ideal magnetohydrodynamic (MHD) fast shocks under magnetic fields of general strength and orientation. The resulting area–Mach-number–shock-angle relation is then incorporated into a numerical method using pseudospectral differentiation. The MHD-GSD model is verified by comparison with results from nonlinear finite-volume solution of the complete ideal MHD equations applied to a shock implosion flow in the presence of an oblique and spatially varying magnetic field ahead of the shock. Results from application of the MHD-GSD equations to the stability of fast MHD shocks in two dimensions are presented. It is shown that the time to formation of triple points for both perturbed MHD and gas-dynamic shocks increases as (Formula presented.), where (Formula presented.) is a measure of the initial Mach-number perturbation. Symmetry breaking in the MHD case is demonstrated. In cylindrical converging geometry, in the presence of an azimuthal field produced by a line current, the MHD shock behaves in the mean as in Pullin et al. (Phys. Fluids, vol. 26, 2014, 097103), but suffers a greater relative pressure fluctuation along the shock than the gas-dynamic shock. © 2016 Cambridge University Press

Geometrical shock dynamics for magnetohydrodynamic fast shocks

KAUST Repository

Mostert, W.

2016-12-12

We describe a formulation of two-dimensional geometrical shock dynamics (GSD) suitable for ideal magnetohydrodynamic (MHD) fast shocks under magnetic fields of general strength and orientation. The resulting area–Mach-number–shock-angle relation is then incorporated into a numerical method using pseudospectral differentiation. The MHD-GSD model is verified by comparison with results from nonlinear finite-volume solution of the complete ideal MHD equations applied to a shock implosion flow in the presence of an oblique and spatially varying magnetic field ahead of the shock. Results from application of the MHD-GSD equations to the stability of fast MHD shocks in two dimensions are presented. It is shown that the time to formation of triple points for both perturbed MHD and gas-dynamic shocks increases as (Formula presented.), where (Formula presented.) is a measure of the initial Mach-number perturbation. Symmetry breaking in the MHD case is demonstrated. In cylindrical converging geometry, in the presence of an azimuthal field produced by a line current, the MHD shock behaves in the mean as in Pullin et al. (Phys. Fluids, vol. 26, 2014, 097103), but suffers a greater relative pressure fluctuation along the shock than the gas-dynamic shock. © 2016 Cambridge University Press

THE CHESS SURVEY OF THE L1157-B1 SHOCK REGION: CO SPECTRAL SIGNATURES OF JET-DRIVEN BOW SHOCKS

Energy Technology Data Exchange (ETDEWEB)

Lefloch, B.; Codella, C.; Ceccarelli, C. [UJF-Grenoble 1/CNRS-INSU, Institut de Planetologie et dAstrophysique de Grenoble (IPAG) UMR 5274, Grenoble, F-38041 (France); Cabrit, S. [Observatoire de Paris, LERMA, UMR 8112 du CNRS, ENS, UPMC, UCP, 61 Av. de l' Observatoire, F-75014 Paris (France); Busquet, G.; Benedettini, M. [INAF, Istituto di Astrofisica e Planetologia Spaziali, Via Fosso del Cavaliere 100, I-00133 Roma (Italy); Cernicharo, J.; Pardo, J. R. [Centro de Astrobiologia, INTA, Ctra de Torrejon a Ajalvir, km 4, E-28850 Torrejon de Ardoz, E-28850 Madrid (Spain); Lis, D. C. [California Institute of Technology, Cahill Center for Astronomy and Astrophysics 301-17, Pasadena, CA 91125 (United States); Nisini, B., E-mail: lefloch@obs.ujf-grenoble.fr [INAF, Osservatorio Astronomico di Roma, Via di Frascati 33, I-00040 Monte, Porzio Catone (Italy)

2012-10-01

The unprecedented sensitivity of Herschel coupled with the high resolution of the HIFI spectrometer permits studies of the intensity-velocity relationship I(v) in molecular outflows, over a higher excitation range than possible up to now. Over the course of the CHESS Key Program, we have observed toward the bright bow shock region L1157-B1, the CO rotational transitions between J = 5-4 and J = 16-15 with HIFI, and the J = 1-0, 2-1, and 3-2 with the IRAM 30 m and the Caltech Submillimeter Observatory telescopes. We find that all the line profiles I{sub CO}(v) are well fit by a linear combination of three exponential laws {proportional_to}exp (- |v/v{sub 0}|) with v{sub 0} = 12.5, 4.4, and 2.5 km s{sup -1}. The first component dominates the CO emission at J {>=} 13, as well as the high-excitation lines of SiO and H{sub 2}O. The second component dominates for 3 {<=} J{sub up} {<=} 10 and the third one for J{sub up} {<=} 2. We show that these exponentials are the signature of quasi-isothermal shocked gas components: the impact of the jet against the L1157-B1 bow shock (T{sub k} {approx_equal} 210 K), the walls of the outflow cavity associated with B1 (T{sub k} {approx_equal} 64 K), and the older cavity L1157-B2 (T{sub k} {approx_equal} 23 K), respectively. Analysis of the CO line flux in the large-velocity gradient approximation further shows that the emission arises from dense gas (n(H{sub 2}) {>=} 10{sup 5}-10{sup 6} cm{sup -3}) close to LTE up to J = 20. We find that the CO J = 2-1 intensity-velocity relation observed in various other molecular outflows is satisfactorily fit by similar exponential laws, which may hold an important clue to their entrainment process.

THE CHESS SURVEY OF THE L1157-B1 SHOCK REGION: CO SPECTRAL SIGNATURES OF JET-DRIVEN BOW SHOCKS

International Nuclear Information System (INIS)

Lefloch, B.; Codella, C.; Ceccarelli, C.; Cabrit, S.; Busquet, G.; Benedettini, M.; Cernicharo, J.; Pardo, J. R.; Lis, D. C.; Nisini, B.

2012-01-01

The unprecedented sensitivity of Herschel coupled with the high resolution of the HIFI spectrometer permits studies of the intensity-velocity relationship I(v) in molecular outflows, over a higher excitation range than possible up to now. Over the course of the CHESS Key Program, we have observed toward the bright bow shock region L1157-B1, the CO rotational transitions between J = 5-4 and J = 16-15 with HIFI, and the J = 1-0, 2-1, and 3-2 with the IRAM 30 m and the Caltech Submillimeter Observatory telescopes. We find that all the line profiles I CO (v) are well fit by a linear combination of three exponential laws ∝exp (– |v/v 0 |) with v 0 = 12.5, 4.4, and 2.5 km s –1 . The first component dominates the CO emission at J ≥ 13, as well as the high-excitation lines of SiO and H 2 O. The second component dominates for 3 ≤ J up ≤ 10 and the third one for J up ≤ 2. We show that these exponentials are the signature of quasi-isothermal shocked gas components: the impact of the jet against the L1157-B1 bow shock (T k ≅ 210 K), the walls of the outflow cavity associated with B1 (T k ≅ 64 K), and the older cavity L1157-B2 (T k ≅ 23 K), respectively. Analysis of the CO line flux in the large-velocity gradient approximation further shows that the emission arises from dense gas (n(H 2 ) ≥ 10 5 -10 6 cm –3 ) close to LTE up to J = 20. We find that the CO J = 2-1 intensity-velocity relation observed in various other molecular outflows is satisfactorily fit by similar exponential laws, which may hold an important clue to their entrainment process.

Cardiogenic shock. Current concepts in management.

Science.gov (United States)

Balakumaran, K; Hugenholtz, P G

1986-10-01

This article presents a categorisation of circulatory shock and discusses the causes, haemodynamics, and clinical recognition of cardiogenic shock. The first step in the management strategy in cardiogenic shock is to guide the patient from the state of shock to one of managed haemodynamic stability. The therapeutic manoeuvres of this first step constitute the management tactics, which can be grouped under 3 general headings: (a) making the most of a malfunctioning heart; (b) improving the state of the heart; and (c) reducing the demands on the heart. In order to make the most of the heart, i.e. to get the highest possible output at the lowest possible cost, clinicians need to use their judgement in stimulating an overtaxed heart on the one hand, and in manipulating the loads on it (the preload and afterload) on the other, for although these methods may be advantageous, they are not without their pitfalls. Efforts to improve the state of the heart often necessitate surgical (e.g. mitral valve replacement) or semisurgical (e.g. coronary angiography and recanalisation) techniques, although intravenous antithrombotic agents may achieve comparable results in a few cases at the bedside. Reducing the demands on the heart is an active process involving the takeover of at least a part of the work of the heart by ancillary devices such as the intra-aortic balloon pump, and of the work of breathing by intubation and artificial ventilation. The individuality of each case of cardiogenic shock emphasises the need for empirical modulation of therapy based on feedback information obtained by haemodynamic monitoring.

Acidic pH shock induces the expressions of a wide range of stress-response genes

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Hong Soon-Kwang

2008-12-01

Full Text Available Abstract Background Environmental signals usually enhance secondary metabolite production in Streptomycetes by initiating complex signal transduction system. It is known that different sigma factors respond to different types of stresses, respectively in Streptomyces strains, which have a number of unique signal transduction mechanisms depending on the types of environmental shock. In this study, we wanted to know how a pH shock would affect the expression of various sigma factors and shock-related proteins in S. coelicolor A3(2. Results According to the results of transcriptional and proteomic analyses, the major number of sigma factor genes were upregulated by an acidic pH shock. Well-studied sigma factor genes of sigH (heat shock, sigR (oxidative stress, sigB (osmotic shock, and hrdD that play a major role in the secondary metabolism, were all strongly upregulated by the pH shock. A number of heat shock proteins including the DnaK family and chaperones such as GroEL2 were also observed to be upregulated by the pH shock, while their repressor of hspR was strongly downregulated. Oxidative stress-related proteins such as thioredoxin, catalase, superoxide dismutase, peroxidase, and osmotic shock-related protein such as vesicle synthases were also upregulated in overall. Conclusion From these observations, an acidic pH shock was considered to be one of the strongest stresses to influence a wide range of sigma factors and shock-related proteins including general stress response proteins. The upregulation of the sigma factors and shock proteins already found to be related to actinorhodin biosynthesis was considered to have contributed to enhanced actinorhodin productivity by mediating the pH shock signal to regulators or biosynthesis genes for actinorhodin production.

Pressurized-thermal-shock experiments: PTSE-1 results and PTSE-2 plans

International Nuclear Information System (INIS)

Bryan, R.H.; Nanstad, R.K.; Wanner, R.; Merkle, J.G.; Robinson, G.C.; Whitman, G.D.

1985-01-01

The first pressurized-thermal-shock experiment (PTSE-1) was performed with a vessel with a 1-m-long flaw in a plug of specially tempered steel having the composition of SA-508 forging steel. The second experiment (PTSE-2) will have a similar arrangement, but the material in which the flaw will be implanted is being prepared to have low tearing resistance. Special tempering of a 2 1/4 Cr - 1 Mo steel plate has been shown to induce a low Charpy impact energy in the upper-shelf temperature range. The purpose of PTSE-2 is to investigate the fracture behavior of low-upper-shelf material in a vessel under the combined loading of concurrent pressure and thermal shock. The primary objective of the experimental plan is to induce a rapidly propagating cleavage fracture under conditions that are likely to induce a ductile tearing instability at the time of arrest of the cleavage fracture. The secondary objective of the test is to extend the range of the investigation of warm prestressing. 11 figs

Letter to the EditorForbush precursory increase and shock-associated particles on 20 October 1989

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A. Struminsky

2002-08-01

Full Text Available Strong interplanetary disturbances may affect cosmic ray protons tremendously with energies less than 1 GeV, increasing their intensity by hundreds of percents, but they are not so effective for protons of higher energies. This energy limit is crucial to understand processes of cosmic ray propagation and acceleration in the heliosphere. The Forbush pre-increase and the effect of shock-associated particles observed on 20 October 1989 illustrate the problem. This is a rare event, when the energies of shock-associated particles measured by the GOES-7 satellite spread continuously to the neutron monitor energies. The Forbush pre-increase could be attributed to a single reflection of galactic cosmic rays from the magnetic wall observed at 12:00 UT. It had a very hard spectrum with maximum energy of modulation more than 10 GeV. The spectrum of shock-associated particles was soft and their maximum energy was less than 1 GeV. The problem of shock acceleration versus trapping is discussed for the 20 October 1989 event. It is argued that the shock-associated particles were accelerated near the flare site and then propagated to the Earth inside the trap between two magnetic walls at 12:00 UT and 17:00 UT.Key words. Interplanetary physics (cosmic rays; energetic particles; interplanetary magnetic fields

MULTI-SPACECRAFT ANALYSIS OF ENERGETIC HEAVY ION AND INTERPLANETARY SHOCK PROPERTIES IN ENERGETIC STORM PARTICLE EVENTS NEAR 1 au

Energy Technology Data Exchange (ETDEWEB)

Ebert, R. W.; Dayeh, M. A.; Desai, M. I. [Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78238 (United States); Jian, L. K. [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Li, G. [The Center for Space Plasma and Aeronomic Research (CSPAR), University of Alabama in Huntsville, Huntsville, AL 35756 (United States); Mason, G. M., E-mail: rebert@swri.edu [Johns Hopkins University/Applied Physics Laboratory, Laurel, MD 20273 (United States)

2016-11-10

We examine the longitude distribution of and relationship between interplanetary (IP) shock properties and ∼0.1–20 MeV nucleon{sup -1} O and Fe ions during seven multi-spacecraft energetic storm particle (ESP) events at 1 au. These ESP events were observed at two spacecraft and were primarily associated with low Mach number, quasi-perpendicular shocks. Key observations include the following: (i) the Alfvén Mach number increased from east to west of the coronal mass ejection source longitude, while the shock speed, compression ratios, and obliquity showed no clear dependence; (ii) the O and Fe time intensity profiles and peak intensities varied significantly between longitudinally separated spacecraft observing the same event, the peak intensities being larger near the nose and smaller along the flank of the IP shock; (iii) the O and Fe peak intensities had weak to no correlations with the shock parameters; (iv) the Fe/O time profiles showed intra-event variations upstream of the shock that disappeared downstream of the shock, where values plateaued to those comparable to the mean Fe/O of solar cycle 23; (v) the O and Fe spectral index ranged from ∼1.0 to 3.4, the Fe spectra being softer in most events; and (vi) the observed spectral index was softer than the value predicted from the shock compression ratio in most events. We conclude that while the variations in IP shock properties may account for some variations in O and Fe properties within these multi-spacecraft events, detailed examination of the upstream seed population and IP turbulence, along with modeling, are required to fully characterize these observations.

Focused tandem shock waves in water and their potential application in cancer treatment

Czech Academy of Sciences Publication Activity Database

Lukeš, Petr; Šunka, Pavel; Hoffer, Petr; Stelmashuk, Vitaliy; Poučková, P.; Zadinová, M.; Zeman, J.; Dibdiak, L.; Kolářová, H.; Tománková, K.; Binder, S.; Beneš, J.

2014-01-01

Roč. 24, č. 1 (2014), s. 51-57 ISSN 0938-1287. [International Symposium on Shock Waves/28./. Manchester, 17.07.2011-22.07.2011] R&D Projects: GA ČR GA202/09/1151 Institutional support: RVO:61389021 Keywords : focused shock waves * underwater discharge * cancer treatment Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 0.885, year: 2014

Electric gun: a new method for generating shock pressures in excess of 1 TPa

International Nuclear Information System (INIS)

Steinberg, D.; Chau, H.; Dittbenner, G.; Weingart, R.

1978-01-01

By combining the electrically-driven, flying-plate, high-explosive initiator with well-known gas-gun technology, a novel method of generating and measuring shock pressures greater than 1 TPa has been developed. Called the electric gun, this system is competitive with laser or nuclear-driven, shock-wave, equation-of-state experiments in the 1 to 5 TPa range. Compared to those other methods, it has the advantage of simplicity, high precision, and low cost. In addition, its small size and low total energy allow it to be easily contained for experiments with toxic materials

Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

Energy Technology Data Exchange (ETDEWEB)

Han, B.; Zhao, Z.G.; Zhang, L.M.; Li, S.G.; Niu, C.Y. [Institute of Microcirculation, Hebei North University, Hebei Zhangjiakou (China)

2015-04-28

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H{sub 2}S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H{sub 2}S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H{sub 2}S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H{sub 2}S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H{sub 2}S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H{sub 2}S and H{sub 2}S-mediated inflammation.

Pediatric Toxic Shock Syndrome

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Jennifer Yee

2017-09-01

Full Text Available Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of a pediatric patient with toxic shock syndrome. The case is also appropriate for teaching of medical students and advanced practice providers, as well as a review of the principles of crisis resource management, teamwork, and communication. Introduction: Toxic shock syndrome is a low-frequency, high-acuity scenario requiring timely identification and aggressive management. If patients suffering from this condition are managed incorrectly, they may progress into multi-organ dysfunction and potentially death. Toxic shock syndrome has been associated with Streptococcus and Staphylococcus aureus (Staph. Approximately half of Staph cases are associated with menstruation, which was first described in the 1970s-1980s and was associated with the use of absorbent tampons.1 Group A Streptococcus may cause complications such as necrotizing fasciitis and gangrenous myositis.2 Pediatric patients may present critically ill from toxic shock syndrome. Providers need to perform a thorough history and physical exam to discern the source of infection. Management requires aggressive care with antibiotics and IV fluids. Objectives: By the end of this simulation session, the learner will be able to: 1 Recognize toxic shock syndrome. 2 Review the importance of a thorough physical exam. 3 Discuss management of toxic shock syndrome, including supportive care and the difference in antibiotic choices for streptococcal and staphylococcal toxic shock syndrome. 4 Appropriately disposition a patient suffering from toxic shock syndrome. 5 Communicate effectively with team members and nursing staff during a resuscitation of a critically ill patient. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on toxic shock syndrome.

A low or high BMI is a risk factor for renal hematoma after extracorporeal shock wave lithotripsy for kidney stones.

Science.gov (United States)

Nussberger, Fabio; Roth, Beat; Metzger, Tobias; Kiss, Bernhard; Thalmann, George N; Seiler, Roland

2017-06-01

The purpose of this study was to evaluate risk factors for renal hematoma after extracorporeal shock wave lithotripsy (SWL) for kidney stones in a matched case-control analysis of a subgroup of patients recruited from a prospective randomized cohort. Between 06/2010 and 03/2013, 418 patients underwent SWL with the MODULITH ® -SLX-F2-lithotripter for kidney stones. In 39/418 patients (9 %), ultrasound at post-treatment day 1 revealed renal hematomas. For 37 of these patients, a matched group without hematoma could be selected according to the following matching criteria: age, gender, number and energy of shock waves, stone burden and localization. Risk factors for renal hematoma after SWL were compared between the two groups. The rates of diabetes, stopped anticoagulant/antiplatelet medications and arterial hypertension were not different between the two groups (p > 0.2). The skin-kidney distance was virtually the same in both groups (p = 0.5). In the hematoma group, significantly more patients had a high (>30: n = 16) as well as a low (hematomas after SWL. Patients with a high (>30) or low (<21.5) BMI had a higher risk for renal damage after SWL. Therefore, alternative endoscopic treatment options should be considered in these patients.

Dynamics of laser ablative shock waves from one dimensional periodic structured surfaces

Science.gov (United States)

Paturi, Prem Kiran; Chelikani, Leela; Pinnoju, Venkateshwarlu; Acrhem Team

2015-06-01

Spatio-temporal evolution of Laser ablative shock waves (LASWs) from one dimensional periodic structured surfaces (1D-PSS) of Aluminum is studied using time resolved defocused shadowgraphy technique. LASWs are generated by focusing 7 ns pulses from second harmonic of Nd:YAG (532 nm, 10 Hz) laser on to 1D-PSS with sinusoidal and triangular modulations of varying periodicity. An expanded He-Ne laser (632.8 nm) is used as probe beam for shadowgraphy. Evolution of ablative shock front (SF) with 1.5 ns temporal resolution is used to measure position of the SF, its nature, density and pressure behind the SF. The effect of surface modulation on the LASW and contact front dynamics was compared to those from a flat surface (FS) of Aluminum. SWs from FS and PSS obeyed Taylor's solution for spherical and planar nature, respectively. The velocity of SF from 1D PSS had a twofold increase compared to the FS. This was further enhanced for structures whose periodicity is of the order of excitation wavelength. Variation of SF properties with varying periodicity over a range of 3.3 μm to 0.55 μm has the potential to tailor shockwaves of required parameters. The work is supported by Defence Research and Developement Organization, India through Grants-in-Aid Program. The periodic surfaces were procured with financial support from BRFST project No. NFP-MAT-A12-04.

NK1.1+ cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock.

Science.gov (United States)

Chen, Shuhua; Hoffman, Rosemary A; Scott, Melanie; Manson, Joanna; Loughran, Patricia; Ramadan, Mostafa; Demetris, Anthony J; Billiar, Timothy R

2017-07-01

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1 + cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1 + cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1 + cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1 + cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut. © Society for Leukocyte Biology.

PIV tracer behavior on propagating shock fronts

International Nuclear Information System (INIS)

Glazyrin, Fyodor N; Mursenkova, Irina V; Znamenskaya, Irina A

2016-01-01

The present work was aimed at the quantitative particle image velocimetry (PIV) measurement of a velocity field near the front of a propagating shock wave and the study of the dynamics of liquid tracers crossing the shock front. For this goal, a shock tube with a rectangular cross-section (48  ×  24 mm) was used. The flat shock wave with Mach numbers M  =  1.4–2.0 propagating inside the tube channel was studied as well as an expanding shock wave propagating outside the channel with M  =  1.2–1.8 at its main axis. The PIV imaging of the shock fronts was carried out with an aerosol of dioctyl sebacate (DEHS) as tracer particles. The pressures of the gas in front of the shock waves studied ranged from 0.013 Mpa to 0.1 MPa in the series of experiments. The processed PIV data, compared to the 1D normal shock theory, yielded consistent values of wake velocity immediately behind the plain shock wave. Special attention was paid to the blurring of the velocity jump on the shock front due to the inertial particle lag and peculiarities of the PIV technique. A numerical algorithm was developed for analysis and correction of the PIV data on the shock fronts, based on equations of particle-flow interaction. By application of this algorithm, the effective particle diameter of the DEHS aerosol tracers was estimated as 1.03  ±  0.12 μm. A number of different formulations for particle drag were tested with this algorithm, with varying success. The results show consistency with previously reported experimental data obtained for cases of stationary shock waves. (paper)

A cryogenic multichannel electronically scanned pressure module

Science.gov (United States)

Shams, Qamar A.; Fox, Robert L.; Adcock, Edward E.; Kahng, Seun K.

1992-01-01

Consideration is given to a cryogenic multichannel electronically scanned pressure (ESP) module developed and tested over an extended temperature span from -184 to +50 C and a pressure range of 0 to 5 psig. The ESP module consists of 32 pressure sensor dice, four analog 8 differential-input multiplexers, and an amplifier circuit, all of which are packaged in a physical volume of 2 x 1 x 5/8 in with 32 pressure and two reference ports. Maximum nonrepeatability is measured at 0.21 percent of full-scale output. The ESP modules have performed consistently well over 15 times over the above temperature range and continue to work without any sign of degradation. These sensors are also immune to repeated thermal shock tests over a temperature change of 220 C/sec.

Gene expression of heat shock protein 70, interleukin-1β and tumor necrosis factor α as tools to identify immunotoxic effects on Xenopus laevis: A dose–response study with benzo[a]pyrene and its degradation products

International Nuclear Information System (INIS)

Martini, Federica; Fernández, Carlos; Tarazona, José V.; Pablos, M. Victoria

2012-01-01

The exposure to benzo[a]pyrene (B[a]P) results in an alteration of immune function in mammals and fish, and the analysis of cytokine mRNA levels has been suggested for predicting the immunomodulatory potential of chemicals. To obtain evidence of the innate immune responses to B[a]P in Xenopus laevis, the present study monitored the mRNA expression of interleukin 1-β (IL-1β), tumor necrosis factor α (TNF-α) and heat shock protein 70 (HSP70) in a laboratorial exposure. Tadpoles exposed to 8.36, 14.64, 89.06 and 309.47 μg/L of B[a]P,were used for detecting hsp70, IL-1β and TNF-α mRNA induction. A dose–response increase in the expression of hsp70 and IL-1β mRNA was found. The results of this study confirmed the use of hsp70 and IL-1β, but not TNF-α, as sensitive indicators of immunotoxic effect of B[a]P in X. laevis. Further research would be required for the validation of these endpoints. - Highlights: ► We study innate immune responses to benzo[a]pyrene in Xenopus laevis. ► mRNA expression of three typical proinflammatory proteins was monitored. ► Heat shock protein 70 mRNA induction showed a concentration/response/time relationship. ► Interleukin 1-β also showed a clear concentration/response relationship. ► Interleukin 1-β and heat shock protein 70 are useful indicators of immunotoxic effects. - The present study analyzed the use of cytokine mRNA levels as an earlier tool for predicting immunotoxicological risks to Xenopus laevis in a dose–response pattern.

Thermal shock behaviour of mullite-cordierite refractory materials

Czech Academy of Sciences Publication Activity Database

Boccaccini, D. N.; Leonelli, C.; Romagnoli, M.; Pellacani, G. C.; Veronesi, P.; Dlouhý, Ivo; Boccaccini, A. R.

2007-01-01

Roč. 106, č. 3 (2007), s. 142-148 ISSN 1743-6753 R&D Projects: GA AV ČR IAA200410502 Institutional research plan: CEZ:AV0Z20410507 Keywords : refraktory materials * thermal shock * fracutre toughness Subject RIV: JH - Ceramics, Fire-Resistant Materials and Glass Impact factor: 1.074, year: 2007

Modulation of integrin-linked kinase (ILK expression in human oesophageal squamous cell carcinoma cell lines by the EGF and TGFβ1 growth factors

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Veale Robin B

2006-04-01

Full Text Available Abstract Background Integrin-linked kinase (ILK is a ubiquitously expressed protein kinase that has emerged as one of the points of convergence between integrin- and growth factor-signalling pathways. Results In this study we identify the ILK isoform expressed in five human oesophageal squamous cell carcinoma cell lines of South African origin as ILK1, and demonstrate its cellular distribution. ILK expression, although similar in the majority of the cell lines, did show variation. Furthermore, the ILK expressed was shown to be catalytically functional. The effect of growth factors on ILK expression was examined. An increase in ILK expression, following EGF and TGFβ1 exposure, was a trend across all the five oesophageal carcinoma cell lines tested. Conclusion These results suggest that growth factor modulation of ILK expression relies on the internalisation/recycling of growth factor receptors and stimulation of the PI3K pathway, which may have implications with regards to cell adhesion and tumourigenesis.

PI3K/AKT signaling modulates transcriptional expression of EWS/FLI1 through specificity protein 1.

Science.gov (United States)

Giorgi, Chiara; Boro, Aleksandar; Rechfeld, Florian; Lopez-Garcia, Laura A; Gierisch, Maria E; Schäfer, Beat W; Niggli, Felix K

2015-10-06

Ewing sarcoma (ES) is the second most frequent bone cancer in childhood and is characterized by the presence of the balanced translocation t(11;22)(q24;q12) in more than 85% of cases, generating a dysregulated transcription factor EWS/FLI1. This fusion protein is an essential oncogenic component of ES development which is necessary for tumor cell maintenance and represents an attractive therapeutic target. To search for modulators of EWS/FLI1 activity we screened a library of 153 targeted compounds and identified inhibitors of the PI3K pathway to directly modulate EWS/FLI1 transcription. Surprisingly, treatment of four different ES cell lines with BEZ235 resulted in down regulation of EWS/FLI1 mRNA and protein by ~50% with subsequent modulation of target gene expression. Analysis of the EWS/FLI1 promoter region (-2239/+67) using various deletion constructs identified two 14 bp minimal elements as being important for EWS/FLI1 transcription. We identified SP1 as modulator of EWS/FLI1 gene expression and demonstrated direct binding to one of these regions in the EWS/FLI1 promoter by EMSA and ChIP experiments. These results provide the first insights on the transcriptional regulation of EWS/FLI1, an area that has not been investigated so far, and offer an additional molecular explanation for the known sensitivity of ES cell lines to PI3K inhibition.

Exploratory laser-driven shock wave studies

International Nuclear Information System (INIS)

Solem, J.C.; Veeser, L.R.

1977-11-01

We show the results of a feasibility study for investigating shock structure and for measuring equation-of-state parameters using high-energy, short-pulse lasers. We discuss the temporal and spatial structure of the luminosity from laser-driven shock unloading in aluminum foils. We demonstrate that shock velocity can be measured by observing the time interval between shock emergence across two thicknesses and show data for shocks of 1.3 and 2.1 Mbar. The fact that we observe shock fronts cleanly breaking through steps as small as 3 μm indicates that the shock front thickness is very small in the few megabar region; this is the first experimental verification that these fronts are not more than a few micrometers thick. We present approximate measurements of free-surface velocity. Finally, we speculate on the use of these techniques to obtain detailed equation-of-state data

Initial ISEE magnetometer results: shock observation

International Nuclear Information System (INIS)

Russell, C.T.

1979-01-01

ISEE-1 and -2 magnetic field profiles across 6 terrestrial bow shock and one interplanetary shock are examined. The inteplanetary shock illustrates the behavior of a low Mach number shock. Three examples of low or moderate β, high Mach number, quasi-perpendicular shocks are examined. These did not have upstream waves, but rather had waves growing in the field gradient. Two examples of high β shocks showed little coherence in field variation even though the two vehicles were only a few hundred kilometers apart. The authors present the joint behavior of wave, particle and field data across some of these shocks to show some of the myriad of shock features whose behavior they are now beginning to investigate. (Auth.)

Compression module for the BCM1F microTCA raw data readout

CERN Document Server

Dostanic, Milica

2017-01-01

BCM1F is a diamond based detector and one of the luminometers and background monitors operated by the BRIL group, part of the CMS experiment. BCM1F's front-end produces analog signals which are digitized in a new microTCA back-end. An FPGA in the back-end part takes care of signal processing and stores raw data. The raw data readout has been improved by implementing a data compression module in the firmware. This module has allowed storing larger amount of data in short time intervals. The module has been implemented in VHDL, using a zero suppression algorithm: only data above a defined threshold is stored into memory, while the samples around the base line are discarded. Thanks to metadata, describing the suppressed data, the shape of input signals and time information are preserved. Tests with simulations and a pulse generator showed good results and proved that the module can achieve large compression factor.

Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.

Science.gov (United States)

Minsky, Neri; Roeder, Robert G

2017-01-06

Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes, and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate the expression of diverse genes encoding secreted molecules and extracellular matrix components to modulate the secretome. Using cell lines, primary cells, and mice, we show that both endogenous and exogenous PGC-1α down-regulate the expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1α on the expression of genes encoding secreted proteins. Interestingly, PGC-1α requires the central heat shock response regulator heat shock factor protein 1 (HSF1) to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1α modulates the secretome of mouse embryonic fibroblasts. Our results define a link between a key pathway controlling metabolic regulation and the regulation of the mammalian secretome. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic Stress Resistance.

Science.gov (United States)

Ene, Iuliana V; Walker, Louise A; Schiavone, Marion; Lee, Keunsook K; Martin-Yken, Hélène; Dague, Etienne; Gow, Neil A R; Munro, Carol A; Brown, Alistair J P

2015-07-28

The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen-activated protein kinase (MAPK) pathways modulate cell wall gene expression, leading to the construction of a new, modified cell wall. We show that the cell wall is not rigid but elastic, displaying rapid structural realignments that impact survival following osmotic shock. Lactate-grown Candida albicans cells are more resistant to hyperosmotic shock than glucose-grown cells. We show that this elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell death occurs within 10 min of osmotic shock. Sudden decreases in cell volume drive rapid increases in cell wall thickness. The elevated stress resistance of lactate-grown cells correlates with reduced cell wall elasticity, reflected in slower changes in cell volume following hyperosmotic shock. The cell wall elasticity of lactate-grown cells is increased by a triple mutation that inactivates the Crh family of cell wall cross-linking enzymes, leading to increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in glucose-grown cells reduces cell wall elasticity, providing partial protection against hyperosmotic shock. These changes correlate with structural realignment of the cell wall and with the ability of cells to withstand osmotic shock. The C. albicans cell wall is the first line of defense against external insults, the site of immune recognition by the host, and an attractive target for antifungal therapy. Its tensile strength is conferred by

Collisionless shock waves

International Nuclear Information System (INIS)

Sagdeev, R.Z.; Kennel, C.F.

1991-01-01

Collisionless shocks cannot occur naturally on the earth, because nearly all matter here consists of electrically neutral atoms and molecules. In space, however, high temperatures and ultraviolet radiation from hot stars decompose atoms into their constituent nuclei and electrons, producing a soup of electrically charged particles known as a plasma. Plasma physicists proposed that the collective electrical and magnetic properties of plasmas could produce interactions that take the place of collisions and permit shocks to form. In 1964 the theoretical work found its first experimental confirmation. Norman F. Ness and his colleagues at the Goddard Space Flight Center, using data collected from the iMP-1 spacecraft, detected clear signs that a collisionless shock exists where the solar wind encounters the earth's magnetic field. More recent research has demonstrated that collisionless shocks appear in a dazzling array of astronomical settings. For example, shocks have been found in the solar wind upstream (sunward) of all the planet and comets that have been visited by spacecraft. Violent flares on the sun generate shocks that propagate to the far reaches of the solar system; tremendous galactic outbursts create disruptions in the intergalactic medium that are trillions of times larger. In addition, many astrophysicists think that shocks from supernova explosions in our galaxy accelerate cosmic rays, a class of extraordinarily energetic elementary particles and atomic nuclei that rain down on the earth from all directions

Physics of Collisionless Shocks Space Plasma Shock Waves

CERN Document Server

Balogh, André

2013-01-01

The present book provides a contemporary systematic treatment of shock waves in high-temperature collisionless plasmas as are encountered in near Earth space and in Astrophysics. It consists of two parts. Part I develops the complete theory of shocks in dilute hot plasmas under the assumption of absence of collisions among the charged particles when the interaction is mediated solely by the self-consistent electromagnetic fields. Such shocks are naturally magnetised implying that the magnetic field plays an important role in their evolution and dynamics. This part treats both subcritical shocks, which dissipate flow energy by generating anomalous resistance or viscosity, and supercritical shocks. The main emphasis is, however, on super-critical shocks where the anomalous dissipation is insufficient to retard the upstream flow. These shocks, depending on the direction of the upstream magnetic field, are distinguished as quasi-perpendicular and quasi-parallel shocks which exhibit different behaviours, reflecti...

Experimental method for laser-driven flyer plates for 1-D shocks

International Nuclear Information System (INIS)

Paisley, D. L.; Luo, S. N.; Swift, D. C.; Loomis, E.; Johnson, R.; Greenfield, S.; Peralta, P.; Koskelo, A.; Tonks, D.

2007-01-01

One-dimensional shocks can be generated by impacting flyer plates accelerated to terminal velocities by a confined laser-ablated plasma. Over the past few years, we have developed this capability with our facility-size laser, TRIDENT, capable of ≥500 Joules at multi-microsecond pulse lengths to accelerate 1-D flyer plates, 8-mm diameter by 0.1-2 mm thick. Plates have been accelerated to terminal velocities of 100 to ≥500 m/s, with full recovery of the flyer and target for post mortem metallography. By properly tailoring the laser temporal and spatial profile, the expanding confined plasma accelerates the plate away from the transparent sapphire substrate, and decouples the laser parameters from shock pressure profile resulting from the plate impact on a target. Since the flyer plate is in free flight on impact with the target, minimal collateral damage occurs to either. The experimental method to launch these plates to terminal velocity, ancillary diagnostics, and representative experimental data is presented

Analysis of Msx1 and Msx2 transactivation function in the context of the heat shock 70 (Hspa1b) gene promoter.

Science.gov (United States)

Zhuang, Fengfeng; Nguyen, Manuel P; Shuler, Charles; Liu, Yi-Hsin

2009-04-03

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent transactivation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and heat shock factors may play a contributing role.

Prediction of massive bleeding. Shock index and modified shock index.

Science.gov (United States)

Terceros-Almanza, L J; García-Fuentes, C; Bermejo-Aznárez, S; Prieto-Del Portillo, I J; Mudarra-Reche, C; Sáez-de la Fuente, I; Chico-Fernández, M

2017-12-01

To determine the predictive value of the Shock Index and Modified Shock Index in patients with massive bleeding due to severe trauma. Retrospective cohort. Severe trauma patient's initial attention at the intensive care unit of a tertiary hospital. Patients older than 14 years that were admitted to the hospital with severe trauma (Injury Severity Score >15) form January 2014 to December 2015. We studied the sensitivity (Se), specificity (Sp), positive and negative predictive value (PV+ and PV-), positive and negative likelihood ratio (LR+ and LR-), ROC curves (Receiver Operating Characteristics) and the area under the same (AUROC) for prediction of massive hemorrhage. 287 patients were included, 76.31% (219) were male, mean age was 43,36 (±17.71) years and ISS was 26 (interquartile range [IQR]: 21-34). The overall frequency of massive bleeding was 8.71% (25). For Shock Index: AUROC was 0.89 (95% confidence intervals [CI] 0.84 to 0.94), with an optimal cutoff at 1.11, Se was 91.3% (95% CI: 73.2 to 97.58) and Sp was 79.69% (95% CI: 74.34 to 84.16). For the Modified Shock Index: AUROC was 0.90 (95% CI: 0.86 to 0.95), with an optimal cutoff at 1.46, Se was 95.65% (95% CI: 79.01 to 99.23) and Sp was 75.78% (95% CI: 70.18 to 80.62). Shock Index and Modified Shock Index are good predictors of massive bleeding and could be easily incorporated to the initial workup of patients with severe trauma. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.

Science.gov (United States)

Borelli, C; Becker, B; Thude, S; Fehrenbacher, B; Isermann, D

2017-12-01

Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis. We analyzed the effect of DRG on the expression of KLK5, LL-37, PAR2, and VEGF in an in vitro skin model of human reconstituted epidermis. The expression of CAMP (LL-37 gene, fold change -4.19 [±0.11]), VEGFA (fold change -2.55 [±0.12]) and PAR2 (-1.33 [±0.12]) was reduced, KLK5 expression increased (fold change 2.06 (±0.08)) after 18 h of treatment with DRG in comparison to treatment with the matrix gel only. The reduction in CAMP expression was significant (P<.01). The protein expression of all four inflammatory markers was markedly reduced after 18 hours of DRG treatment in comparison to baseline (0 hour), by measure of fluorescence intensity. We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable. © 2017 Wiley Periodicals, Inc.

Shock modification and chemistry and planetary geologic processes

International Nuclear Information System (INIS)

Boslough, M.S.

1991-01-01

This paper brings the rapid advances on shock processing of materials to the attention of Earth scientists, and to put these advances in the context of planetary geologic processes. Most of the recent research in this area has been directed at materials modification an synthesis, and the information gained has direct relevance to shock effects in nature. Research on various types of shock modification and chemistry in both naturally and experimentally shocked rocks and minerals is reviewed, and where appropriate their significance to planetary processes is indicated. As a case study, the surface of Mars is suggested as a place where conditions are optimal for shock processing to be a dominant factor. The various mechanisms of shock modification, activation, synthesis and decomposition are all proposed as major contributors to the evolution of chemical, mineralogical, and physical properties of the Martian regolith

Alpha Power Modulates Perception Independently of Endogenous Factors

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Sasskia Brüers

2018-04-01

Full Text Available Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF, a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution. Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between

Microstructure in two- and three-dimensional hybrid simulations of perpendicular collisionless shocks

Czech Academy of Sciences Publication Activity Database

Burgess, D.; Hellinger, Petr; Gingell, I.; Trávníček, Pavel M.

2016-01-01

Roč. 82, č. 4 (2016), 905820401/1-905820401/23 ISSN 0022-3778 Institutional support: RVO:68378289 Keywords : ion-acceleration * numerical simulations * bow shock * electron acceleration * cluster observations * self-reformation * magnetic-field * whistler waves * injection * nonstationarity Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.160, year: 2016 https://www.cambridge.org/core/ journals /journal-of-plasma-physics/article/microstructure-in-two-and-three-dimensional-hybrid-simulations-of-perpendicular-collisionless-shocks/F964EF89FB14A6504A49CFAD54970E2B

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast.

Directory of Open Access Journals (Sweden)

Michelle D Leach

2012-12-01

Full Text Available Thermal adaptation is essential in all organisms. In yeasts, the heat shock response is commanded by the heat shock transcription factor Hsf1. Here we have integrated unbiased genetic screens with directed molecular dissection to demonstrate that multiple signalling cascades contribute to thermal adaptation in the pathogenic yeast Candida albicans. We show that the molecular chaperone heat shock protein 90 (Hsp90 interacts with and down-regulates Hsf1 thereby modulating short term thermal adaptation. In the longer term, thermal adaptation depends on key MAP kinase signalling pathways that are associated with cell wall remodelling: the Hog1, Mkc1 and Cek1 pathways. We demonstrate that these pathways are differentially activated and display cross talk during heat shock. As a result ambient temperature significantly affects the resistance of C. albicans cells to cell wall stresses (Calcofluor White and Congo Red, but not osmotic stress (NaCl. We also show that the inactivation of MAP kinase signalling disrupts this cross talk between thermal and cell wall adaptation. Critically, Hsp90 coordinates this cross talk. Genetic and pharmacological inhibition of Hsp90 disrupts the Hsf1-Hsp90 regulatory circuit thereby disturbing HSP gene regulation and reducing the resistance of C. albicans to proteotoxic stresses. Hsp90 depletion also affects cell wall biogenesis by impairing the activation of its client proteins Mkc1 and Hog1, as well as Cek1, which we implicate as a new Hsp90 client in this study. Therefore Hsp90 modulates the short term Hsf1-mediated activation of the classic heat shock response, coordinating this response with long term thermal adaptation via Mkc1- Hog1- and Cek1-mediated cell wall remodelling.

Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock.

Science.gov (United States)

Collin, Solène; Sennoun, Nacira; Dron, Anne-Gaëlle; de la Bourdonnaye, Mathilde; Montemont, Chantal; Asfar, Pierre; Lacolley, Patrick; Meziani, Ferhat; Levy, Bruno

2011-05-01

To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular K(ATP) (PNU-37883A) or BK(Ca) [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular K(ATP) channels, while expression of vascular BK(Ca) channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular K(ATP) channel expression. Vascular K(ATP) but not BK(Ca) channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular K(ATP) channel inhibitors offer potential therapeutic perspectives for septic shock.

The Cold Shock Domain of YB-1 Segregates RNA from DNA by Non-Bonded Interactions.

Directory of Open Access Journals (Sweden)

Vladislav Kljashtorny

Full Text Available The human YB-1 protein plays multiple cellular roles, of which many are dictated by its binding to RNA and DNA through its Cold Shock Domain (CSD. Using molecular dynamics simulation approaches validated by experimental assays, the YB1 CSD was found to interact with nucleic acids in a sequence-dependent manner and with a higher affinity for RNA than DNA. The binding properties of the YB1 CSD were close to those observed for the related bacterial Cold Shock Proteins (CSP, albeit some differences in sequence specificity. The results provide insights in the molecular mechanisms whereby YB-1 interacts with nucleic acids.

PINK1 positively regulates IL-1β-mediated signaling through Tollip and IRAK1 modulation

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Lee Hyun Jung

2012-12-01

Full Text Available Abstract Background Parkinson disease (PD is characterized by a slow, progressive degeneration of dopaminergic neurons in the substantianigra. The cause of neuronal loss in PD is not well understood, but several genetic loci, including PTEN-induced putative kinase 1 (PINK1, have been linked to early-onset autosomal recessive forms of familial PD. Neuroinflammation greatly contributes to PD neuronal degeneration and pathogenesis. IL-1 is one of the principal cytokines that regulates various immune and inflammatory responses via the activation of the transcription factors NF-κB and activating protein-1. Despite the close relationship between PD and neuroinflammation, the functional roles of PD-linked genes during inflammatory processes remain poorly understood. Methods To explore the functional roles of PINK1 in response to IL-1β stimulation, HEK293 cells, mouse embryonic fibroblasts derived from PINK1-null (PINK1−/− and control (PINK1+/+ mice, and 293 IL-1RI cells stably expressing type 1 IL-1 receptor were used. Immunoprecipitation and western blot analysis were performed to detect protein–protein interaction and protein ubiquitination. To confirm the effect of PINK1 on NF-κB activation, NF-κB-dependent firefly luciferase reporter assay was conducted. Results PINK1 specifically binds two components of the IL-1-mediated signaling cascade, Toll-interacting protein (Tollip and IL-1 receptor-associated kinase 1 (IRAK1. The association of PINK1 with Tollip, a negative regulator of IL-1β signaling, increases upon IL-1β stimulation, which then facilitates the dissociation of Tollip from IRAK1 as well as the assembly of the IRAK1–TNF receptor-associated factor 6 (TRAF6 complex. PINK1 also enhances Lys63-linked polyubiquitination of IRAK1, an essential modification of recruitment of NF-κB essential modulator and subsequent IκB kinase activation, and increases formation of the intermediate signalosome including IRAK1, TRAF6, and

Diaphragmless shock wave generators for industrial applications of shock waves

Science.gov (United States)

Hariharan, M. S.; Janardhanraj, S.; Saravanan, S.; Jagadeesh, G.

2011-06-01

The prime focus of this study is to design a 50 mm internal diameter diaphragmless shock tube that can be used in an industrial facility for repeated loading of shock waves. The instantaneous rise in pressure and temperature of a medium can be used in a variety of industrial applications. We designed, fabricated and tested three different shock wave generators of which one system employs a highly elastic rubber membrane and the other systems use a fast acting pneumatic valve instead of conventional metal diaphragms. The valve opening speed is obtained with the help of a high speed camera. For shock generation systems with a pneumatic cylinder, it ranges from 0.325 to 1.15 m/s while it is around 8.3 m/s for the rubber membrane. Experiments are conducted using the three diaphragmless systems and the results obtained are analyzed carefully to obtain a relation between the opening speed of the valve and the amount of gas that is actually utilized in the generation of the shock wave for each system. The rubber membrane is not suitable for industrial applications because it needs to be replaced regularly and cannot withstand high driver pressures. The maximum shock Mach number obtained using the new diaphragmless system that uses the pneumatic valve is 2.125 ± 0.2%. This system shows much promise for automation in an industrial environment.

Multi-Shock Shield Performance at 15 MJ for Catalogued Debris

Science.gov (United States)

Miller, J. E.; Davis, B. A.; Christiansen, E. L.; Lear, D. M.

2015-01-01

While orbital debris of ten centimeters or more are tracked and catalogued, the difficulty of finding and accurately accounting for forces acting on the objects near the ten centimeter threshold results in both uncertainty of their presence and location. These challenges result in difficult decisions for operators balancing potential costly operational approaches with system loss risk. In this paper, the assessment of the feasibility of protecting a spacecraft from this catalogued debris is described using numerical simulations and a test of a multi-shock shield system against a cylindrical projectile impacting normal to the surface with approximately 15 MJ of kinetic energy. The hypervelocity impact test has been conducted at the Arnold Engineering Development Complex (AEDC) with a 598 g projectile at 6.905 km/s on a NASA supplied multi-shock shield. The projectile used is a hollow aluminum and nylon cylinder with an outside diameter of 8.6 cm and length of 10.3 cm. Figure 1 illustrates the multi-shock shield test article, which consisted of five separate bumpers, four of which are fiberglass fabric and one of steel mesh, and two rear walls, each consisting of Kevlar fabric. The overall length of the test article was 2.65 m. The test article was a 5X scaled-up version of a smaller multi-shock shield previously tested using a 1.4 cm diameter aluminum projectile for an inflatable module project. The distances represented by S1 and S1/2 in the figure are 61 cm and 30.5 cm, respectively. Prior to the impact test, hydrodynamic simulations indicated that some enhancement to the standard multi-shock system is needed to address the effects of the cylindrical shape of the projectile. Based on the simulations, a steel mesh bumper has been added to the shield configuration to enhance the fragmentation of the projectile. The AEDC test occurred as planned, and the modified NASA multi-shock shield successfully stopped 598 g projectile using 85.6 kg/m(exp 2). The fifth bumper

Magnetic field fluctuations across the Earth's bow shock

Energy Technology Data Exchange (ETDEWEB)

Czaykowska, A.; Bauer, T.M. [Max-Planck-Institut fuer Extraterrestrische Physik, Garching (Germany); Treumann, R.A. [Max-Planck-Institut fuer Extraterrestrische Physik, Garching (Germany); Centre for Interdisciplinary Plasma Science, Garching (Germany); International Space Science Inst. (ISSI), Bern (Switzerland); Baumjohann, W. [Max-Planck-Institut fuer Extraterrestrische Physik, Garching (Germany); Inst. fuer Weltraumforschung der Oesterreichischen Akademie der Wissenschaften, Graz (Austria)

2001-03-01

We present a statistical analysis of 132 dayside (LT 0700-1700) bow shock crossings of the AMPTE/IRM spacecraft. We perform a superposed epoch analysis of low frequency, magnetic power spectra some minutes upstream and downstream of the bow shock. The events are devided into categories depending on the angle {theta}{sub Bn} between bow shock normal and interplanetary magnetic field, and on plasma-{beta}. In the foreshock upstream of the quasi-parallel bow shock, the power of the magnetic fluctuations is roughly 1 order of magnitude larger ({delta}B {proportional_to} 4 nT for frequencies 0.01-0.04 Hz) than upstream of the quasi-perpendicular shock. There is no significant difference in the magnetic power spectra upstream and downstream of the quasi-parallel bow shock; only at the shock itself, is the magnetic power enhanced by a factor of 4. This enhancement may be due to either an amplification of convecting upstream waves or to wave generation at the shock interface. On the contrary, downstream of the quasi-perpendicular shock, the magnetic wave activity is considerably higher than upstream. Downstream of the quasi-perpendicular low-{beta} bow shock, we find a dominance of the left-hand polarized component at frequencies just below the ion-cyclotron frequency, with amplitudes of about 3 nT. These waves are identified as ion-cyclotron waves, which grow in a low-{beta} regime due to the proton temperature anisotropy. We find a strong correlation of this anisotropy with the intensity of the left-hand polarized component. Downstream of some nearly perpendicular ({theta}{sub Bn} {approx} 90 ) high-{beta} crossings, mirror waves are identified. However, there are also cases where the conditions for mirror modes are met downstream of the nearly perpendicular shock, but no mirror waves are observed. (orig.)

Transient shocks beyond the heliopause

International Nuclear Information System (INIS)

Fermo, R L; Pogorelov, N V; Burlaga, L F

2015-01-01

The heliopause is a rich, dynamic surface affected by the time-dependent solar wind. Stream interactions due to coronal mass ejections (CMEs), corotating interaction regions (CIRs), and other transient phenomena are known to merge producing global merged interaction regions (GMIRs). Numerical simulations of the solar wind interaction with the local interstellar medium (LISM) show that GMIRs, as well other time-dependent structures in the solar wind, may produce compression/rarefaction waves and shocks in the LISM behind the heliopause. These shocks may initiate wave activity observed by the Voyager spacecraft. The magnetometer onboard Voyager 1 indeed observed a few structures that may be interpreted as shocks. We present numerical simulations of such shocks in the year of 2000, when both Voyager spacecraft were in the supersonic solar wind region, and in 2012, when Voyager 1 observed traveling shocks. In the former case, Voyager observations themselves provide time- dependent boundary conditions in the solar wind. In the latter case, we use OMNI data at 1 AU to analyze the plasma and magnetic field behavior after Voyager 1 crossed the heliospheric boundary. Numerical results are compared with spacecraft observations. (paper)

On the stability of bow shocks generated by red supergiants: the case of IRC -10414

Science.gov (United States)

Meyer, D. M.-A.; Gvaramadze, V. V.; Langer, N.; Mackey, J.; Boumis, P.; Mohamed, S.

2014-03-01

In this Letter, we explore the hypothesis that the smooth appearance of bow shocks around some red supergiants (RSGs) might be caused by the ionization of their winds by external sources of radiation. Our numerical simulations of the bow shock generated by IRC -10414 (the first-ever RSG with an optically detected bow shock) show that the ionization of the wind results in its acceleration by a factor of 2, which reduces the difference between the wind and space velocities of the star and makes the contact discontinuity of the bow shock stable for a range of stellar space velocities and mass-loss rates. Our best-fitting model reproduces the overall shape and surface brightness of the observed bow shock and suggests that the space velocity and mass-loss rate of IRC -10414 are ≈50 km s-1 and ≈10-6 M⊙ yr-1, respectively, and that the number density of the local interstellar medium is ≈3 cm-3. It also shows that the bow shock emission comes mainly from the shocked stellar wind. This naturally explains the enhanced nitrogen abundance in the line-emitting material, derived from the spectroscopy of the bow shock. We found that photoionized bow shocks are ≈15-50 times brighter in optical line emission than their neutral counterparts, from which we conclude that the bow shock of IRC -10414 must be photoionized.

Simulations of Converging Shock Collisions for Shock Ignition

Science.gov (United States)

Sauppe, Joshua; Dodd, Evan; Loomis, Eric

2016-10-01

Shock ignition (SI) has been proposed as an alternative to achieving high gain in inertial confinement fusion (ICF) targets. A central hot spot below the ignition threshold is created by an initial compression pulse, and a second laser pulse drives a strong converging shock into the fuel. The collision between the rebounding shock from the compression pulse and the converging shock results in amplification of the converging shock and increases the hot spot pressure above the ignition threshold. We investigate shock collision in SI drive schemes for cylindrical targets with a polystyrene foam interior using radiation-hydrodynamics simulations with the RAGE code. The configuration is similar to previous targets fielded on the Omega laser. The CH interior results in a lower convergence ratio and the cylindrical geometry facilitates visualization of the shock transit using an axial X-ray backlighter, both of which are important for comparison to potential experimental measurements. One-dimensional simulations are used to determine shock timing, and the effects of low mode asymmetries in 2D computations are also quantified. LA-UR-16-24773.

Bow shock specularly reflected ions in the presence of low-frequency electromagnetic waves: a case study

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K. Meziane

2004-07-01

Full Text Available An energetic ion (E≤40 event observed by the CLUSTER/CIS experiment upstream of the Earth's bow shock is studied in detail. The ion event is observed in association with quasi-monochromatic ULF MHD-like waves, which we show modulate the ion fluxes. According to three statistical bow shock position models, the Cluster spacecrafts are located at ~0.5 Re from the shock and the averaged bow shock θBn0 is about ~30°. The analysis of the three-dimensional angular distribution indicates that ions propagating roughly along the magnetic field direction are observed at the onset of the event. Later on, the angular distribution is gyrophase-bunched and the pitch-angle distribution is peaked at α0~θBn0, consistent with the specular reflection production mechanism. The analysis of the waves shows that they are left-handed in the spacecraft frame of reference (right-handed in the solar wind frame and propagate roughly along the ambient magnetic field; we have found that they are in cyclotron-resonance with the field-aligned beam observed just upstream. Using properties of the waves and particles, we explain the observed particle flux-modulation in the context of θBn changes at the shock caused by the convected ULF waves. We have found that the high count rates coincide with particles leaving the shock when θBn angles are less than ~40°, consistent with the specular reflection hypothesis as the production mechanism of ions.

Magnetic field fluctuations across the Earth’s bow shock

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A. Czaykowska

Full Text Available We present a statistical analysis of 132 dayside (LT 0700-1700 bow shock crossings of the AMPTE/IRM spacecraft. We perform a superposed epoch analysis of low frequency, magnetic power spectra some minutes up-stream and downstream of the bow shock. The events are devided into categories depending on the angle θ_Bn between bow shock normal and interplanetary magnetic field, and on plasma-β. In the foreshock upstream of the quasi-parallel bow shock, the power of the magnetic fluctuations is roughly 1 order of magnitude larger (δB ~ 4 nT for frequencies 0.01–0.04 Hz than upstream of the quasi-perpendicular shock. There is no significant difference in the magnetic power spectra upstream and downstream of the quasi-parallel bow shock; only at the shock itself, is the magnetic power enhanced by a factor of 4. This enhancement may be due to either an amplification of convecting upstream waves or to wave generation at the shock interface. On the contrary, downstream of the quasi-perpendicular shock, the magnetic wave activity is considerably higher than upstream. Down-stream of the quasi-perpendicular low-β bow shock, we find a dominance of the left-hand polarized component at frequencies just below the ion-cyclotron frequency, with amplitudes of about 3 nT. These waves are identified as ion-cyclotron waves, which grow in a low-β regime due to the proton temperature anisotropy. We find a strong correlation of this anisotropy with the intensity of the left-hand polarized component. Downstream of some nearly perpendicular (θ_Bn ≈ 90° high-β crossings, mirror waves are identified. However, there are also cases where the conditions for mirror modes are met downstream of the nearly perpendicular shock, but no mirror waves are observed.

Key words. Interplanetary physics (plasma waves and turbulence – Magnetospheric physics (magnetosheath; plasma waves and

Magnetic field fluctuations across the Earth’s bow shock

Directory of Open Access Journals (Sweden)

A. Czaykowska

2001-03-01

Full Text Available We present a statistical analysis of 132 dayside (LT 0700-1700 bow shock crossings of the AMPTE/IRM spacecraft. We perform a superposed epoch analysis of low frequency, magnetic power spectra some minutes up-stream and downstream of the bow shock. The events are devided into categories depending on the angle θBn between bow shock normal and interplanetary magnetic field, and on plasma-β. In the foreshock upstream of the quasi-parallel bow shock, the power of the magnetic fluctuations is roughly 1 order of magnitude larger (δB ~ 4 nT for frequencies 0.01–0.04 Hz than upstream of the quasi-perpendicular shock. There is no significant difference in the magnetic power spectra upstream and downstream of the quasi-parallel bow shock; only at the shock itself, is the magnetic power enhanced by a factor of 4. This enhancement may be due to either an amplification of convecting upstream waves or to wave generation at the shock interface. On the contrary, downstream of the quasi-perpendicular shock, the magnetic wave activity is considerably higher than upstream. Down-stream of the quasi-perpendicular low-β bow shock, we find a dominance of the left-hand polarized component at frequencies just below the ion-cyclotron frequency, with amplitudes of about 3 nT. These waves are identified as ion-cyclotron waves, which grow in a low-β regime due to the proton temperature anisotropy. We find a strong correlation of this anisotropy with the intensity of the left-hand polarized component. Downstream of some nearly perpendicular (θBn ≈ 90° high-β crossings, mirror waves are identified. However, there are also cases where the conditions for mirror modes are met downstream of the nearly perpendicular shock, but no mirror waves are observed.Key words. Interplanetary physics (plasma waves and turbulence – Magnetospheric physics (magnetosheath; plasma waves and instabilities

Variable field-to-normal angles in the shock foreshock boundary observed by ISEE 1 and 2

International Nuclear Information System (INIS)

Greenstadt, E.W.; Mellot, M.M.

1985-01-01

Saturated ULF waves in the foreshock, with amplitudes comparable to the magnitude of the average field, are convected by the solar wind to the quasi-parallel shock where the average field-normal angle is less than, or about, 45 0 . Several examples from ISEE 1 and 2 magnetometer data show waves that defined local, instantaneous field-normal angles very different periodically from the average. Local geometric conditions at the nominally quasi-parallel shock varied from nearly parallel to nearly perpendicular, at the periods of typical upstream waves. Clear magnetic shock transitions occurred under temporarily quasi-perpendicular geometry

Relation between total shock energy and mortality in patients with implantable cardioverter-defibrillator.

Science.gov (United States)

Tenma, Taro; Yokoshiki, Hisashi; Mitsuyama, Hirofumi; Watanabe, Masaya; Mizukami, Kazuya; Kamada, Rui; Takahashi, Masayuki; Sasaki, Ryo; Maeno, Motoki; Okamoto, Kaori; Chiba, Yuki; Anzai, Toshihisa

2018-05-15

Implantable Cardioverter-Defibrillator (ICD) shocks have been associated with mortality. However, no study has examined the relation between total shock energy and mortality. The aim of this study is to assess the association of total shock energy with mortality, and to determine the patients who are at risk of this association. Data from 316 consecutive patients who underwent initial ICD implantation in our hospital between 2000 and 2011 were retrospectively studied. We collected shock energy for 3 years from the ICD implantation, and determined the relation of shock energy on mortality after adjusting confounding factors. Eighty-seven ICD recipients experienced shock(s) within 3 years from ICD implantation and 43 patients had died during the follow-up. The amount of shock energy was significantly associated with all-cause death [adjusted hazard ratio (HR) 1.26 (per 100 joule increase), p energy accumulation (≥182 joule) was lower (p energy accumulation (energy accumulation and all-cause death was remarkable in the patients with low left ventricular ejection fraction (LVEF ≤40%) or atrial fibrillation (AF). Increase of shock energy was related to mortality in ICD recipients. This relation was evident in patients with low LVEF or AF. Copyright © 2018 Elsevier B.V. All rights reserved.

Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation.

Science.gov (United States)

Borowiec, Anne-Sophie; Sion, Benoit; Chalmel, Frédéric; D Rolland, Antoine; Lemonnier, Loïc; De Clerck, Tatiana; Bokhobza, Alexandre; Derouiche, Sandra; Dewailly, Etienne; Slomianny, Christian; Mauduit, Claire; Benahmed, Mohamed; Roudbaraki, Morad; Jégou, Bernard; Prevarskaya, Natalia; Bidaux, Gabriel

2016-09-01

Testes of most male mammals present the particularity of being externalized from the body and are consequently slightly cooler than core body temperature (4-8°C below). Although, hypothermia of the testis is known to increase germ cells apoptosis, little is known about the underlying molecular mechanisms, including cold sensors, transduction pathways, and apoptosis triggers. In this study, using a functional knockout mouse model of the cold and menthol receptors, dubbed transient receptor potential melastatine 8 (TRPM8) channels, we found that TRPM8 initiated the cold-shock response by differentially modulating cold- and heat-shock proteins. Besides, apoptosis of germ cells increased in proportion to the cooling level in control mice but was independent of temperature in knockout mice. We also observed that the rate of germ cell death correlated positively with the reactive oxygen species level and negatively with the expression of the detoxifying enzymes. This result suggests that the TRPM8 sensor is a key determinant of germ cell fate under hypothermic stimulation.-Borowiec, A.-S., Sion, B., Chalmel, F., Rolland, A. D., Lemonnier, L., De Clerck, T., Bokhobza, A., Derouiche, S., Dewailly, E., Slomianny, C., Mauduit, C., Benahmed, M., Roudbaraki, M., Jégou, B., Prevarskaya, N., Bidaux, G. Cold/menthol TRPM8 receptors initiate the cold-shock response and protect germ cells from cold-shock-induced oxidation. © The Author(s).

Shock Protection of Portable Electronic Products: Shock Response Spectrum, Damage Boundary Approach, and Beyond

Directory of Open Access Journals (Sweden)

Suresh Goyal

1997-01-01

Full Text Available The pervasive shock response spectrum (SRS and damage boundary methods for evaluating product fragility and designing external cushioning for shock protection are described in detail with references to the best available literature. Underlying assumptions are carefully reviewed and the central message of the SRS is highlighted, particularly as it relates to standardized drop testing. Shortcomings of these methods are discussed, and the results are extended to apply to more general systems. Finally some general packaging and shock-mounting strategies are discussed in the context of protecting a fragile disk drive in a notebook computer, although the conclusions apply to other products as well. For example, exterior only cushioning (with low restitution to reduce subsequent impacts will provide a slenderer form factor than the next best strategy: interior cushioning with a “dead” hard outer shell.

THE EFFECT OF A DYNAMIC INNER HELIOSHEATH THICKNESS ON COSMIC-RAY MODULATION

International Nuclear Information System (INIS)

Manuel, R.; Ferreira, S. E. S.; Potgieter, M. S.

2015-01-01

The time-dependent modulation of galactic cosmic rays in the heliosphere is studied over different polarity cycles by computing 2.5 GV proton intensities using a two-dimensional, time-dependent modulation model. By incorporating recent theoretical advances in the relevant transport parameters in the model, we showed in previous work that this approach gave realistic computed intensities over a solar cycle. New in this work is that a time dependence of the solar wind termination shock (TS) position is implemented in our model to study the effect of a dynamic inner heliosheath thickness (the region between the TS and heliopause) on the solar modulation of galactic cosmic rays. The study reveals that changes in the inner heliosheath thickness, arising from a time-dependent shock position, does affect cosmic-ray intensities everywhere in the heliosphere over a solar cycle, with the smallest effect in the innermost heliosphere. A time-dependent TS position causes a phase difference between the solar activity periods and the corresponding intensity periods. The maximum intensities in response to a solar minimum activity period are found to be dependent on the time-dependent TS profile. It is found that changing the width of the inner heliosheath with time over a solar cycle can shift the time of when the maximum or minimum cosmic-ray intensities occur at various distances throughout the heliosphere, but more significantly in the outer heliosphere. The time-dependent extent of the inner heliosheath, as affected by solar activity conditions, is thus an additional time-dependent factor to be considered in the long-term modulation of cosmic rays

Conversion of piston-driven shocks from powerful solar flares to blast wave shocks in the solar wind

International Nuclear Information System (INIS)

Pinter, S.

1990-01-01

It was suggested by Smart and Shea (1985) that the time of arrival of solar-flare-generated shock waves at any point in space may be predicted by assuming that they are first driven from the Sun after which they decay into blast shocks. Their study was extended by using the duration of the Type IV radio emission as a phenomenological symptom of the piston-driven phase of these shocks. Using a sample of 39 cases of combined Type II/Type IV observations from 1972 to 1982 solar flares, it was found that the average predicted times-of-arrival of these shocks to Earth (and elsewhere) deviate from the actual times by 1.40 hr with a standard deviation of 1.25 hr. On the average, a representative shock from this sample is emitted from a powerful flare with a velocity of 1,560 km sec -1 ; moves at a constant inertial velocity to a distance of 0.12 AU after which it begins to decelerate as a classical (Sedov-type) blast shock that is convected by the ambient solar wind as suggested by Smart and Shea; and arrives to Earth 45.8 hr after its initiation in the Sun. Shocks that appear to deviate from this phenomenological scenario by virtue of lack of detection on Earth are assumed to decay into fast mode MHD waves. (author). 7 figs., 1 tab., 53 refs

Resonant ion acceleration by collisionless magnetosonic shock waves

International Nuclear Information System (INIS)

Ohsawa, Y.

1985-01-01

Resonant ion acceleration ( the ν/sub rho/xΒ acceleration ) in laminar magnetosonic shock waves is studied by theory and simulation. Theoretical analysis based on a two-fluid model shows that, in laminar shocks, the electric field strength in the direction of the wave normal is about (m/sub i/m/sub e/) 1 2 times large for quasi-perpendicular shocks than that for the quasi-parallel shocks, which is a reflection of the fact that the width of quasi-perpendicular shocks is much smaller than that of the quasi-parallel shocks. Trapped ions can be accelerated up to the speed about ν/sub A/(m/sub i/m/sub e/) 1 2(M/sub A/-1) 3 2 in quasi-perpendicular shocks. Time evolution of self-consistent magnetosonic shock waves is studied by using a 2-12 dimensional fully relativistic, fully electromagnetic particle simulation with full ion and electron dynamics. Even a low-Mach-number shock wave can significantly accelerate trapped ions by the ν/sub rho/xΒ acceleration. The resonant ion acceleration occurs more strongly in quasi-perpendicular shocks, because the magnitude of this acceleration is proportional to the electric field strength

Solution structure of GSP13 from Bacillus subtilis exhibits an S1 domain related to cold shock proteins

International Nuclear Information System (INIS)

Yu Wenyu; Hu Jicheng; Yu Bingke; Xia Wei; Jin Changwen; Xia Bin

2009-01-01

GSP13 encoded by gene yugI is a σ B -dependent general stress protein in Bacillus subtilis, which can be induced by heat shock, salt stress, ethanol stress, glucose starvation, oxidative stress and cold shock. Here we report the solution structure of GSP13 and it is the first structure of S1 domain containing protein in Bacillus subtilis. The structure of GSP13 mainly consists of a typical S1 domain along with a C-terminal 50-residue flexible tail, different from the other known S1 domain containing proteins. Comparison with other S1 domain structures reveals that GSP13 has a conserved RNA binding surface, and it may function similarly to cold shock proteins in response to cold stress

Shock Dynamics in Stellar Outbursts. I. Shock Formation

Energy Technology Data Exchange (ETDEWEB)

Ro, Stephen; Matzner, Christopher D., E-mail: ro@astro.utoronto.ca [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON M5S 3H4 (Canada)

2017-05-20

Wave-driven outflows and non-disruptive explosions have been implicated in pre-supernova outbursts, supernova impostors, luminous blue variable eruptions, and some narrow-line and superluminous supernovae. To model these events, we investigate the dynamics of stars set in motion by strong acoustic pulses and wave trains, focusing on nonlinear wave propagation, shock formation, and an early phase of the development of a weak shock. We identify the shock formation radius, showing that a heuristic estimate based on crossing characteristics matches an exact expansion around the wave front and verifying both with numerical experiments. Our general analytical condition for shock formation applies to one-dimensional motions within any static environment, including both eruptions and implosions. We also consider the early phase of shock energy dissipation. We find that waves of super-Eddington acoustic luminosity always create shocks, rather than damping by radiative diffusion. Therefore, shock formation is integral to super-Eddington outbursts.

Space Vector Modulation for an Indirect Matrix Converter with Improved Input Power Factor

Directory of Open Access Journals (Sweden)

Nguyen Dinh Tuyen

2017-04-01

Full Text Available Pulse width modulation strategies have been developed for indirect matrix converters (IMCs in order to improve their performance. In indirect matrix converters, the LC input filter is used to remove input current harmonics and electromagnetic interference problems. Unfortunately, due to the existence of the input filter, the input power factor is diminished, especially during operation at low voltage outputs. In this paper, a new space vector modulation (SVM is proposed to compensate for the input power factor of the indirect matrix converter. Both computer simulation and experimental studies through hardware implementation were performed to verify the effectiveness of the proposed modulation strategy.

Anyalysis of Msx1 and Msx2 Transactivation Function in the Context of the Heat Shock 70 (Hspa1b) Gene Promoter

Science.gov (United States)

Zhuang, Fengfeng; Nguyen, Manuel P.; Shuler, Charles; Liu, Yi-Hsin

2009-01-01

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent trans-activation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and Heat shock factors may play a contributing role. PMID:19338779

The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Gabriela Huelgas-Morales

2016-04-01

Full Text Available In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germline—the immortal cell lineage required for sexual reproduction—protection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the Caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation; protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures.

The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock in Caenorhabditis elegans.

Science.gov (United States)

Huelgas-Morales, Gabriela; Silva-García, Carlos Giovanni; Salinas, Laura S; Greenstein, David; Navarro, Rosa E

2016-04-07

In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germline-the immortal cell lineage required for sexual reproduction-protection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the Caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation; protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures. Copyright © 2016 Huelgas-Morales et al.

Generation of Pc 1 waves by the ion temperature anisotropy associated with fast shocks caused by sudden impulses

International Nuclear Information System (INIS)

Mandt, M.E.; Lee, L.C.

1991-01-01

Observations have reported on the high correlation of Pc 1 events with magnetospheric compressions. A number of mechanisms have been suggested for the generation of the Pc 1 waves. In this paper, the authors propose a new mechanism which leads to the generation of Pc 1 waves. The interaction of a dynamic pressure pulse (Δρυ 2 ) with the Earth's bow shock leads to the formation of a weak fast mode shock propagating into the magnetosheath. The shock wave can pass right through a tangential discontinuity (magnetopause) and into the magnetosphere, without disturbing either of the structures. In a quasi-perpendicular geometry, the shock wave exhibits anisotropic heating with T perpendicular > T parallel . This anisotropy drives unstable ion cyclotron waves which they believe can contribute to the generation of the Pc 1 waves which are detected. The viability of the mechanism is demonstrated with simulations. This mechanism could explain peak in the occurrence of observed Pc 1 waves in the postnoon sector where a field-aligned discontinuity in the solar wind would most often be parallel to the magnetopause surface due to the average Parker spiral magnetic field configuration

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex.

Science.gov (United States)

Hennessy, Morgan L; Corcoran, Andrea E; Brust, Rachael D; Chang, YoonJeung; Nattie, Eugene E; Dymecki, Susan M

2017-02-15

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 ( Tac1 ) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1 , referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine -N- oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO 2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO 2 Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using

Condensed matter at high shock pressures

International Nuclear Information System (INIS)

Nellis, W.J.; Holmes, N.C.; Mitchell, A.C.; Radousky, H.B.; Hamilton, D.

1985-01-01

Experimental techniques are described for shock waves in liquids: Hugoniot equation-of-state, shock temperature and emission spectroscopy, electrical conductivity, and Raman spectroscopy. Experimental data are reviewed and presented in terms of phenomena that occur at high densities and temperatures in shocked He, Ar, N 2 , CO, SiO 2 -aerogel, H 2 O, and C 6 H 6 . The superconducting properties of Nb metal shocked to 100 GPa (1 Mbar) and recovered intact are discussed in terms of prospects for synthesizing novel, metastable materials. Ultrahigh pressure data for Cu is reviewed in the range 0.3 to 6TPa (3 to 60 Mbar). 56 refs., 9 figs., 1 tab

Mechanical response of shock conditioned HPNS-5 (R-1) grout

International Nuclear Information System (INIS)

Plannerer, H.N.

1997-01-01

HPNS-5 (R-1) grout is a portland cement formulated mix designed for use as a rigid containment plug in vertical boreholes at the Nevada Test Site. Coincident with field testing of this grout in 1991 and 1992 , two arums of the grout mix were collected and positioned in the by pass drift of the DISTANT ZENITH event to expose the grout to passage of a nuclear driven stress wave. The drums were later retrieved to determine the mechanical behavior of the shock conditioned grout. Sealed hollow tubes positioned within the grout-filled drums to detect ductile flow on passage of the stress wave were found partially to completely filled with HPNS-5 grout following the experiment. Static mechanical tests support the evidence for ductile flow and place the transition from brittle fracture failure to ductile behavior in the shock conditioned grout at a confining stress between ambient and 5 MPa (725 psi). Uniaxial and triaxial tests delineated a stress-strain field for interstice collapse that interposes between the mechanics of linear elastic deformation and dilatancy. Hydrostatic stress loading between 25 MPa (3.6 ksi) and 60 MPa (8.7 ksi) results in a significant change of permanent set from 1% to greater than 15% volume strain

Detection of toxic shock toxin (tst gene in Staphylococcus aureus isolated from bovine milk samples

Directory of Open Access Journals (Sweden)

S. Baniardalan

2017-09-01

Full Text Available Staphylococcus aureus is a major causative pathogen of clinical and subclinical mastitis in dairy cattle all over the world. This agent produces a variety of extracellular toxins and virulence factors in-cluding toxic shock syndrome toxin-1 (TSST-1 which is the major cause of toxic shock syndrome (TSS. In the present study, 76 S. aureus isolates have been obtained from milk samples collected from 7 dairy herds in Hamedan province of Iran. The isolates were identified based on the biochemical and molecular methods using PCR amplification of the femA gene. The staphylococcal isolates were also examined for the presence of TSST-1 (tst encoding gene. This gene was detected in only one S. aureus isolate (1.3%. The results revealed that S. aureus strains causing bovine mastitis may potentially produce staphylococcal toxic shock syndrome toxin-1, indicating that it is very important to follow the presence of TSST-1 producing S. aureus isolates in foodstuffs to protect consumers against the risk of toxic shock syndrome

An alternatively spliced heat shock transcription factor, OsHSFA2dI, functions in the heat stress-induced unfolded protein response in rice.

Science.gov (United States)

Cheng, Q; Zhou, Y; Liu, Z; Zhang, L; Song, G; Guo, Z; Wang, W; Qu, X; Zhu, Y; Yang, D

2015-03-01

As sessile organisms, plants have evolved a wide range of defence pathways to cope with environmental stress such as heat shock. However, the molecular mechanism of these defence pathways remains unclear in rice. In this study, we found that OsHSFA2d, a heat shock transcriptional factor, encodes two main splice variant proteins, OsHSFA2dI and OsHSFA2dII in rice. Under normal conditions, OsHSFA2dII is the dominant but transcriptionally inactive spliced form. However, when the plant suffers heat stress, OsHSFA2d is alternatively spliced into a transcriptionally active form, OsHSFA2dI, which participates in the heat stress response (HSR). Further study found that this alternative splicing was induced by heat shock rather than photoperiod. We found that OsHSFA2dI is localised to the nucleus, whereas OsHSFA2dII is localised to the nucleus and cytoplasm. Moreover, expression of the unfolded protein response (UNFOLDED PROTEIN RESPONSE) sensors, OsIRE1, OsbZIP39/OsbZIP60 and the UNFOLDED PROTEIN RESPONSE marker OsBiP1, was up-regulated. Interestingly, OsbZIP50 was also alternatively spliced under heat stress, indicating that UNFOLDED PROTEIN RESPONSE signalling pathways were activated by heat stress to re-establish cellular protein homeostasis. We further demonstrated that OsHSFA2dI participated in the unfolded protein response by regulating expression of OsBiP1. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Shock interaction with a two-gas interface in a novel dual-driver shock tube

Science.gov (United States)

Labenski, John R.

Fluid instabilities exist at the interface between two fluids having different densities if the flow velocity and density gradient are anti-parallel or if a shock wave crosses the boundary. The former case is called the Rayleigh-Taylor (R-T) instability and the latter, the Richtmyer-Meshkov (R-M) instability. Small initial perturbations on the interface destabilize and grow into larger amplitude structures leading to turbulent mixing. Instabilities of this type are seen in inertial confinement fusion (ICF) experiments, laser produced plasmas, supernova explosions, and detonations. A novel dual-driver shock tube was used to investigate the growth rate of the R-M instability. One driver is used to create an argon-refrigerant interface, and the other at the opposite end of the driven section generates a shock to force the interface with compressible flows behind the shock. The refrigerant gas in the first driver is seeded with sub-micron oil droplets for visualization of the interface. The interface travels down the driven section past the test section for a fixed amount of time. A stronger shock of Mach 1.1 to 1.3 drives the interface back past the test section where flow diagnostics are positioned. Two schlieren systems record the density fluctuations while light scattering detectors record the density of the refrigerant as a function of position over the interface. A pair of digital cameras take stereo images of the interface, as mapped out by the tracer particles under illumination by a Q-switched ruby laser. The amount of time that the interface is allowed to travel up the driven section determines the interaction time as a control. Comparisons made between the schlieren signals, light scattering detector outputs, and the images quantify the fingered characteristics of the interface and its growth due to shock forcing. The results show that the interface has a distribution of thickness and that the interaction with a shock further broadens the interface. The

Hydrodynamic modelling of the shock ignition scheme for inertial confinement fusion

International Nuclear Information System (INIS)

Vallet, Alexandra

2014-01-01

The shock ignition concept in inertial confinement fusion uses an intense power spike at the end of an assembly laser pulse. The key features of shock ignition are the generation of a high ablation pressure, the shock pressure amplification by at least a factor of a hundred in the cold fuel shell and the shock coupling to the hot-spot. In this thesis, new semi-analytical hydrodynamic models are developed to describe the ignitor shock from its generation up to the moment of fuel ignition. A model is developed to describe a spherical converging shock wave in a pre-heated hot spot. The self-similar solution developed by Guderley is perturbed over the shock Mach number Ms ≥≥1. The first order correction accounts for the effects of the shock strength. An analytical ignition criterion is defined in terms of the shock strength and the hot-spot areal density. The ignition threshold is higher when the initial Mach number of the shock is lower. A minimal shock pressure of 20 Gbar is needed when it enters the hot-spot. The shock dynamics in the imploding shell is then analyzed. The shock is propagating into a non inertial medium with a high radial pressure gradient and an overall pressure increase with time. The collision with a returning shock coming from the assembly phase enhances further the ignitor shock pressure. The analytical theory allows to describe the shock pressure and strength evolution in a typical shock ignition implosion. It is demonstrated that, in the case of the HiPER target design, a generation shock pressure near the ablation zone on the order of 300-400 Mbar is needed. An analysis of experiments on the strong shock generation performed on the OMEGA laser facility is presented. It is shown that a shock pressure close to 300 Mbar near the ablation zone has been reached with an absorbed laser intensity up to 2 * 10 15 W:cm -2 and a laser wavelength of 351 nm. This value is two times higher than the one expected from collisional laser absorption only

14-3-3σ induces heat shock protein 70 expression in hepatocellular carcinoma

International Nuclear Information System (INIS)

Liu, Chia-Chia; Wang, John; Shyue, Song-Kun; Sung, Li-Ying; Liou, Jun-Yang; Jan, Yee-Jee; Ko, Bor-Sheng; Wu, Yao-Ming; Liang, Shu-Man; Chen, Shyh-Chang; Lee, Yen-Ming; Liu, Tzu-An; Chang, Tzu-Ching

2014-01-01

14-3-3σ is implicated in promoting tumor development of various malignancies. However, the clinical relevance of 14-3-3σ in hepatocellular carcinoma (HCC) tumor progression and modulation and pathway elucidation remain unclear. We investigated 14-3-3σ expression in 109 HCC tissues by immunohistochemistry. Overexpression and knockdown experiments were performed by transfection with cDNA or siRNA. Protein expression and cell migration were determined by Western blot and Boyden chamber assay. In this study, we found that 14-3-3σ is abundantly expressed in HCC tumors. Stable or transient overexpression of 14-3-3σ induces the expression of heat shock factor-1α (HSF-1α) and heat shock protein 70 (HSP70) in HCC cells. Moreover, expression of 14-3-3σ significantly correlates with HSF-1α/HSP70 in HCC tumors and both 14-3-3σ and HSP70 overexpression are associated with micro-vascular thrombi in HCC patients, suggesting that 14-3-3σ/HSP70 expression is potentially involved in cell migration/invasion. Results of an in vitro migration assay indicate that 14-3-3σ promotes cell migration and that 14-3-3σ-induced cell migration is impaired by siRNA knockdown of HSP70. Finally, 14-3-3σ-induced HSF-1α/HSP70 expression is abolished by the knockdown of β-catenin or activation of GSK-3β. Our findings indicate that 14-3-3σ participates in promoting HCC cell migration and tumor development via β-catenin/HSF-1α/HSP70 pathway regulation. Thus, 14-3-3σ alone or combined with HSP70 are potential prognostic biomarkers for HCC

Comparative Study between Slow Shock Wave Lithotripsy and Fast Shock Wave Lithotripsy in the Management of Renal Stone

Directory of Open Access Journals (Sweden)

AKM Zamanul Islam Bhuiyan

2013-01-01

Full Text Available Background: Renal calculi are frequent causes of ureteric colic. Extracorporeal shock wave lithotripsy is the most common treatment of these stones. It uses focused sound waves to break up stones externally. Objective: To compare the efficiency of slow and fast delivery rate of shock waves on stone fragmentation and treatment outcome in patients with renal calculi. Materials and Methods: This prospective study was done in the department of Urology, National Institute of Kidney diseases and Urology, Sher-e-Bangla Nagar, Dhaka from July 2006 to June 2007. Total 90 patients were treated using the Storz Medical Modulith ® SLX lithotripter. Patients were divided into Group A, Group B and Group C – each group having 30 subjects. Group A was selected for extracorporeal shockwave lithotripsy (ESWL by 60 shock waves per minute, Group B by 90 shock waves per minute and Group C by 120 shock waves per minute. Results: Complete clearance of stone was observed in 24 patients in Group A and 13 patients in both Group B and Group C in first session. In Group A only 3 patients needed second session but in Group B and Group C, 12 and 8 patients needed second session. In Group A only one patient needed third session but third session was required for 3 patients in Group B and 5 patients in Group C for complete clearance of stone. In Group A, subsequent sessions were performed under spinal anesthesia and in Group B under sedation and analgesia (p>0.001. Mean number of sessions for full clearance of stones in group A was 1.37 ± 0.85, in Group B was 1.8 ± 0.887 and in Group C was 2.0 ± 1.083. Significant difference was observed in term of sessions among groups (p>0.05. In first follow-up, complete clearance of stones was seen in 24 patients in Group A and 13 in both Group B and Group C. In second follow-up, 3 patients in Group A, 12 in Group B and 8 in Group C showed complete clearance of stones. It was observed that rate of stone clearance was higher in Group A

Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin.

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Sidhartha M Chafekar

Full Text Available The molecular mechanisms by which polyglutamine (polyQ-expanded huntingtin (Htt causes neurodegeneration in Huntington's disease (HD remain unclear. The malfunction of cellular proteostasis has been suggested as central in HD pathogenesis and also as a target of therapeutic interventions for the treatment of HD. We present results that offer a previously unexplored perspective regarding impaired proteostasis in HD. We find that, under non-stress conditions, the proteostatic capacity of cells expressing full length polyQ-expanded Htt is adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt impairs the heat shock response, a key component of cellular proteostasis. This impaired heat shock response results in a reduced capacity to withstand the damage caused by cellular stress. We demonstrate that in cells expressing polyQ-expanded Htt the levels of heat shock transcription factor 1 (HSF1 are reduced, and, as a consequence, these cells have an impaired a heat shock response. Also, we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when compared to wild-type mice. Our results suggests that full length, non-aggregated polyQ-expanded Htt blocks the effective induction of the heat shock response under stress conditions and may thus trigger the accumulation of cellular damage during the course of HD pathogenesis.

Shock diffraction in alumina powder

International Nuclear Information System (INIS)

Venz, G.; Killen, P.D.; Page, N.W.

1996-01-01

In order to produce complex shaped components by dynamic compaction of ceramic powders detailed knowledge of their response under shock loading conditions is required. This work attempts to provide data on release effects and shock attenuation in 1 μm and 5 μm α-alumina powders which were compacted to between 85 % and 95 % of the solid phase density by the impact of high velocity steel projectiles. As in previous work, the powder was loaded into large cylindrical dies with horizontal marker layers of a contrasting coloured powder to provide a record of powder displacement in the recovered specimens. After recovery and infiltration with a thermosetting resin the specimens were sectioned and polished to reveal the structure formed by the passage of the projectile and shock wave. Results indicate that the shock pressures generated were of the order of 0.5 to 1.4 GPa and higher, with shock velocities and sound speeds in the ranges 650 to 800 m/s and 350 to 400 m/s respectively

Shock-Induced and Shock-Assisted Reaction Synthesis of Materials

National Research Council Canada - National Science Library

Thadhani, N. N

1997-01-01

The beneficial effects of shock-compression of powders and solid-state chemical reactions were utilized to synthesize Ti-Si and Ti-A1 intermetallics, Ti-B and Ti-C ceramics, and Ti-Si:Ti-A1 composites...

Jet formation in shock-heavy gas bubble interaction

Institute of Scientific and Technical Information of China (English)

Zhi-Gang Zhai; Ting Si; Li-Yong Zou; Xi-Sheng Luo

2013-01-01

The influences of the acoustic impedance and shock strength on the jet formation in shock-heavy gas bubble interaction are numerically studied in this work.The process of a shock interacting with a krypton or a SF6 bubble is studied by the numerical method VAS2D.As a validation,the experiments of a SF6 bubble accelerated by a planar shock were performed.The results indicate that,due to the mismatch of acoustic impedance,the way of jet formation in heavy gas bubble with different species is diversified under the same initial condition.With respect to the same bubble,the manner of jet formation is also distinctly different under different shock strengths.The disparities of the acoustic impedance result in different effects of shock focusing in the bubble,and different behaviors of shock wave inside and outside the bubble.The analyses of the wave pattern and the pressure variation indicate that the jet formation is closely associated with the pressure perturbation.Moreover,the analysis of the vorticity deposition,and comparisons of circulation and baroclinic torque show that the baroclinic vorticity also contributes to the jet formation.It is concluded that the pressure perturbation and baroclinic vorticity deposition are the two dominant factors for the jet formation in shock-heavy gas bubble interaction.

Chondrule destruction in nebular shocks

Energy Technology Data Exchange (ETDEWEB)

Jacquet, Emmanuel; Thompson, Christopher, E-mail: ejacquet@mnhn.fr [Canadian Institute for Theoretical Astrophysics, University of Toronto, 60 St George Street, Toronto, ON M5S 3H8 (Canada)

2014-12-10

Chondrules are millimeter-sized silicate spherules ubiquitous in primitive meteorites, but whose origin remains mysterious. One of the main proposed mechanisms for producing them is melting of solids in shock waves in the gaseous protoplanetary disk. However, evidence is mounting that chondrule-forming regions were enriched in solids well above solar abundances. Given the high velocities involved in shock models, destructive collisions would be expected between differently sized grains after passage of the shock front as a result of differential drag. We investigate the probability and outcome of collisions of particles behind a one-dimensional shock using analytic methods as well as a full integration of the coupled mass, momentum, energy, and radiation equations. Destruction of protochondrules seems unavoidable for solid/gas ratios ε ≳ 0.1, and possibly even for solar abundances because of 'sandblasting' by finer dust. A flow with ε ≳ 10 requires much smaller shock velocities (∼2 versus 8 km s{sup –1}) in order to achieve chondrule-melting temperatures, and radiation trapping allows slow cooling of the shocked fragments. Initial destruction would still be extensive; although re-assembly of millimeter-sized particles would naturally occur by grain sticking afterward, the compositional heterogeneity of chondrules may be difficult to reproduce. We finally note that solids passing through small-scale bow shocks around few kilometer-sized planetesimals might experience partial melting and yet escape fragmentation.

Role of echocardiography in reducing shock reversal time in pediatric septic shock: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Ahmed A. EL-Nawawy

Full Text Available Abstract Objective: To evaluate the role of echocardiography in reducing shock reversal time in pediatric septic shock. Methods: A prospective study conducted in the pediatric intensive care unit of a tertiary care teaching hospital from September 2013 to May 2016. Ninety septic shock patients were randomized in a 1:1 ratio for comparing the serial echocardiography-guided therapy in the study group with the standard therapy in the control group regarding clinical course, timely treatment, and outcomes. Results: Shock reversal was significantly higher in the study group (89% vs. 67%, with significantly reduced shock reversal time (3.3 vs. 4.5 days. Pediatric intensive care unit stay in the study group was significantly shorter (8 ± 3 vs. 14 ± 10 days. Mortality due to unresolved shock was significantly lower in the study group. Fluid overload was significantly lower in the study group (11% vs. 44%. In the study group, inotropes were used more frequently (89% vs. 67% and initiated earlier (12[0.5-24] vs. 24[6-72] h with lower maximum vasopressor inotrope score (120[30-325] vs. 170[80-395], revealing predominant use of milrinone (62% vs. 22%. Conclusion: Serial echocardiography provided crucial data for early recognition of septic myocardial dysfunction and hypovolemia that was not apparent on clinical assessment, allowing a timely management and resulting in shock reversal time reduction among children with septic shock.

Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

Science.gov (United States)

Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

2016-01-01

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. Copyright © 2015

A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.

Science.gov (United States)

Wang, B; Liu, Y; Huang, L; Chen, J; Li, J J; Wang, R; Kim, E; Chen, Y; Justicia, C; Sakata, K; Chen, H; Planas, A; Ostrom, R S; Li, W; Yang, G; McDonald, M P; Chen, R; Heck, D H; Liao, F-F

2017-07-01

Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer's disease, without noticeable systemic toxicity. Despite a short half-life of OS47720 in mouse brain, a single intraperitoneal injection induces rapid and long-lasting (>3 days) nuclear activation of the heat-shock factor, HSF1. Mechanistic study indicates that the remedial effects of OS47720 depend upon HSF1 activation and the subsequent HSF1-mediated transcriptional events on synaptic genes. Taken together, this work reveals a novel role of HSF1 in synaptic function and memory, which likely occurs through modulation of the synaptic transcriptome.

Crew Factors in Flight Operations XV: Alertness Management in General Aviation Education Module

Science.gov (United States)

Rosekind, Mark R.; Co, Elizabeth L.; Neri, David F.; Oyung, Raymond L.; Mallis, Melissa M.; Cannon, Mary M. (Technical Monitor)

2002-01-01

Regional operations encompass a broad range of pilots and equipment. This module is intended to help all those involved in regional aviation, including pilots, schedulers, dispatchers, maintenance technicians, policy makers, and others, to understand the physiological factors underlying fatigue, how flight operations affect fatigue, and what can be done to counteract fatigue and maximize alertness and performance in their operations. The overall purpose of this module is to promote aviation safety, performance, and productivity. It is intended to meet three specific objectives: (1) to explain the current state of knowledge about the physiological mechanisms underlying fatigue; (2) to demonstrate how this knowledge can be applied to improving flight crew sleep, performance, and alertness; and (3) to offer strategies for alertness management. Aviation Safety Reporting System (ASRS) and National Transportation Safety Board (NISH) reports are used throughout this module to demonstrate that fatigue is a safety issue in the regional operations community. The appendices at the end of this module include the ASRS reports used for the examples contained in this publication, brief introductions to sleep disorders and relaxation techniques, summaries of relevant NASA publications, and a list of general readings on sleep, sleep disorders, and circadian rhythms.

Condensed matter at high shock pressures

Energy Technology Data Exchange (ETDEWEB)

Nellis, W.J.; Holmes, N.C.; Mitchell, A.C.; Radousky, H.B.; Hamilton, D.

1985-07-12

Experimental techniques are described for shock waves in liquids: Hugoniot equation-of-state, shock temperature and emission spectroscopy, electrical conductivity, and Raman spectroscopy. Experimental data are reviewed and presented in terms of phenomena that occur at high densities and temperatures in shocked He, Ar, N/sub 2/, CO, SiO/sub 2/-aerogel, H/sub 2/O, and C/sub 6/H/sub 6/. The superconducting properties of Nb metal shocked to 100 GPa (1 Mbar) and recovered intact are discussed in terms of prospects for synthesizing novel, metastable materials. Ultrahigh pressure data for Cu is reviewed in the range 0.3 to 6TPa (3 to 60 Mbar). 56 refs., 9 figs., 1 tab.

ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock.

Science.gov (United States)

Aletti, Federico; Conti, Costanza; Ferrario, Manuela; Ribas, Vicent; Bollen Pinto, Bernardo; Herpain, Antoine; Post, Emiel; Romay Medina, Eduardo; Barlassina, Cristina; de Oliveira, Eliandre; Pastorelli, Roberta; Tedeschi, Gabriella; Ristagno, Giuseppe; Taccone, Fabio S; Schmid-Schönbein, Geert W; Ferrer, Ricard; De Backer, Daniel; Bendjelid, Karim; Baselli, Giuseppe

2016-01-28

The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock. Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1  5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses. ShockOmics will provide new insights into the pathophysiological mechanisms underlying shock as well as new biomarkers for the timely diagnosis of cardiac dysfunction in shock and quantitative indices for assisting the therapeutic management of shock patients.

Money velocity in an endogenous growth business cycle with credit shocks

Czech Academy of Sciences Publication Activity Database

Benk, S.; Gillman, M.; Kejak, Michal

2008-01-01

Roč. 40, č. 6 (2008), s. 1281-1293 ISSN 0022-2879 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : money velocity * business cycle * credit shocks Subject RIV: AH - Economics Impact factor: 1.422, year: 2008

The Dynamics of Very High Alfvén Mach Number Shocks in Space Plasmas

Energy Technology Data Exchange (ETDEWEB)

Sundberg, Torbjörn; Burgess, David [School of Physics and Astronomy, Queen Mary University of London, London, E1 4NS (United Kingdom); Scholer, Manfred [Max-Planck-Institut für extraterrestrische Physik, Garching (Germany); Masters, Adam [The Blackett Laboratory, Imperial College London, Prince Consort Road, London, SW7 2AZ (United Kingdom); Sulaiman, Ali H., E-mail: torbjorn.sundberg@gmail.com [Department of Physics and Astronomy, University of Iowa, Iowa City, Iowa 52242 (United States)

2017-02-10

Astrophysical shocks, such as planetary bow shocks or supernova remnant shocks, are often in the high or very-high Mach number regime, and the structure of such shocks is crucial for understanding particle acceleration and plasma heating, as well inherently interesting. Recent magnetic field observations at Saturn’s bow shock, for Alfvén Mach numbers greater than about 25, have provided evidence for periodic non-stationarity, although the details of the ion- and electron-scale processes remain unclear due to limited plasma data. High-resolution, multi-spacecraft data are available for the terrestrial bow shock, but here the very high Mach number regime is only attained on extremely rare occasions. Here we present magnetic field and particle data from three such quasi-perpendicular shock crossings observed by the four-spacecraft Cluster mission. Although both ion reflection and the shock profile are modulated at the upstream ion gyroperiod timescale, the dominant wave growth in the foot takes place at sub-proton length scales and is consistent with being driven by the ion Weibel instability. The observed large-scale behavior depends strongly on cross-scale coupling between ion and electron processes, with ion reflection never fully suppressed, and this suggests a model of the shock dynamics that is in conflict with previous models of non-stationarity. Thus, the observations offer insight into the conditions prevalent in many inaccessible astrophysical environments, and provide important constraints for acceleration processes at such shocks.

High strain rate deformation and fracture of the magnesium alloy Ma2-1 under shock wave loading

Science.gov (United States)

Garkushin, G. V.; Kanel', G. I.; Razorenov, S. V.

2012-05-01

This paper presents the results of measurements of the dynamic elastic limit and spall strength under shock wave loading of specimens of the magnesium alloy Ma2-1 with a thickness ranging from 0.25 to 10 mm at normal and elevated (to 550°C) temperatures. From the results of measurements of the decay of the elastic precursor of a shock compression wave, it has been found that the plastic strain rate behind the front of the elastic precursor decreases from 2 × 105 s-1 at a distance of 0.25 mm to 103 s-1 at a distance of 10 mm. The plastic strain rate in a shock wave is one order of magnitude higher than that in the elastic precursor at the same value of the shear stress. The spall strength of the alloy decreases as the solidus temperature is approached.

Significance of Environmental Density in Shocked Poststarburst Galaxy Evolution

Science.gov (United States)

Jaliff, Laura

2018-01-01

The Shocked POstarbusrt Galaxy Survey (SPOGS) comprises 1,066 galaxies undergoing the transformation from blue cloud late-type spirals to red sequence non-star-forming early-type ellipticals and lenticulars. They are selected via spectral analysis of ionized gas line ratios, which indicate shocked objects, and Balmer H-δ equivalent width, which select recently formed stars, but not active star formation. E+A galaxies (Zabludoff et al. 1996), like SPOGs, contain young stars but, unlike SPOGs, no emission lines consistent with star formation. They differ in that the quality used to discern SPOGs, their shocks, produces H-α lines that prevent them from being found via the same criteria as E+As. Thus, SPOGs can be found before being entirely stripped of their gas, and, while E+As are largely red and dead, found leaving the green valley, SPOGS are mostly entering it. The environmental density data for SPOGs was retrieved via the NASA Extragalactic Database (NED) radial velocity constrained cone tool, which provides counts and densities within spheres of radii 1, 5, and 10 Mpc from the center of search as well as relative positions and redshifts of objects. The kinematic morphology-density relation (Cappellari et al. 2011) is employed as a point of comparison for how SPOGs’ environmental densities might relate to morphological and spectroscopic factors, including tidal features, asymmetry, and color, in order to fully understand the role of environmental factors in SPOGS object evolution.

Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.

Directory of Open Access Journals (Sweden)

Sophie Joly

Full Text Available Interferon Regulatory Factor (IRF 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.

Radiation exposure to patients during extracorporeal shock wave lithotripsy

International Nuclear Information System (INIS)

Van Swearingen, F.L.; McCullough, D.L.; Dyer, R.; Appel, B.

1987-01-01

Extracorporeal shock wave lithotripsy is rapidly becoming an accepted treatment of renal calculi. Since fluoroscopy is involved to image the stones it is important to know how much radiation the patient receives during this procedure. Surface radiation exposure to the patient was measured in more than 300 fluoroscopic and radiographic procedures using thermoluminescent dosimeters. Initial results showed an average skin exposure of 10.1 rad per procedure for each x-ray unit, comparing favorably with exposure rates for percutaneous nephrostolithotomy and other routine radiological procedures. Factors influencing exposure levels include stone characteristics (location, size and opacity), physician experience and number of shocks required. Suggestions are given that may result in a 50 per cent reduction of radiation exposure

H2 profiles of C-type bow shocks

International Nuclear Information System (INIS)

Smith, M.D.; Brand, P.W.J.L.

1990-01-01

We present emission-line profiles of molecular hydrogen from curved C-shocks within molecular clouds. Shock configurations arising from the supersonic motion of jets and bullets within a dense cloud are chosen. Bow shock speeds in the range υ w = 40-200 km s -1 are investigated. Breakdown through dissociation and self-ionization restricts the C-shock section to the bow tail. We find that profiles are essentially single-peaked and narrow with full widths (at 10 per cent maximum intensity, deconvolved) of up to about 50, 40 and 30 km s -1 for cones, hemispherical caps and paraboloids, respectively. Exceptional field alignments can produce lines as wide as 75 km s -1 in the conical shock model. (author)

Thermal Shielding Effects of a Damaged Shock Absorber and an Intact Shock Absorber

Energy Technology Data Exchange (ETDEWEB)

Bang, K. S.; Lee, J. C.; Kim, K. Y.; Seo, C. S.; Seo, K. S. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2011-05-15

In order to safely transport the radioactive waste arising from the hot test of an ACP(Advanced Spent Fuel Conditioning Process) a shipping package is required. Therefore, KAERI is developing a shipping package to transport the radioactive waste arising from the ACPF during a hot test. The regulatory requirements for a Type B package are specified in the Korea Most Act 2009-37, IAEA Safety Standard Series No. TS-R-1, and US 10 CFR Part. These regulatory guidelines classify the hot cell cask as a Type B package, and state that the Type B package for transporting radioactive materials should be able to withstand a test sequence consisting of a 9 m drop onto an unyielding surface, a 1 m drop onto a puncture bar, and a 30 minute fully engulfing fire. Greiner et al. investigated the thermal protection provided by shock absorbers by using the CAFE computer code. To evaluate the thermal shielding effect of the shock absorber, the thermal test was performed by using a 1/2 scale model with a shock absorber which was damaged by both a 9 m drop test and a 1 m puncture test. For the purpose of comparison, the thermal test was also carried out by using a 1/2 scale model with the intact shock absorber

WRAP Module 1 waste characterization plan

International Nuclear Information System (INIS)

Mayancsik, B.A.

1995-01-01

The purpose of this document is to present the characterization methodology for waste generated, processed, or otherwise the responsibility of the Waste Receiving and Processing (WRAP) Module 1 facility. The scope of this document includes all solid low level waste (LLW), transuranic (TRU), mixed waste (MW), and dangerous waste. This document is not meant to be all-inclusive of the waste processed or generated within WRAP Module 1, but to present a methodology for characterization. As other streams are identified, the method of characterization will be consistent with the other streams identified in this plan. The WRAP Module 1 facility is located in the 200 West Area of the Hanford Site. The facility's function is two-fold. The first is to verify/characterize, treat and repackage contact handled (CH) waste currently in retrievable storage in the LLW Burial Grounds, Hanford Central Waste Complex, and the Transuranic Storage and Assay Facility (TRUSAF). The second is to verify newly generated CH TRU waste and LLW, including MW. The WRAP Module 1 facility provides NDE and NDA of the waste for both drums and boxes. The NDE is used to identify the physical contents of the waste containers to support waste characterization and processing, verification, or certification. The NDA results determine the radioactive content and distribution of the waste

Toxic shock syndrome

Science.gov (United States)

Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

Learning with three factors: modulating Hebbian plasticity with errors.

Science.gov (United States)

Kuśmierz, Łukasz; Isomura, Takuya; Toyoizumi, Taro

2017-10-01

Synaptic plasticity is a central theme in neuroscience. A framework of three-factor learning rules provides a powerful abstraction, helping to navigate through the abundance of models of synaptic plasticity. It is well-known that the dopamine modulation of learning is related to reward, but theoretical models predict other functional roles of the modulatory third factor; it may encode errors for supervised learning, summary statistics of the population activity for unsupervised learning or attentional feedback. Specialized structures may be needed in order to generate and propagate third factors in the neural network. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Particle Acceleration in Two Converging Shocks

Energy Technology Data Exchange (ETDEWEB)

Wang, Xin; Wang, Na; Shan, Hao [Xinjiang Astronomical Observatory, Chinese Academy of Sciences, Urumqi 830011 (China); Giacalone, Joe [Lunar and Planetary Laboratory, University of Arizona, Tucson AZ 85721 (United States); Yan, Yihua [CAS Key Laboratory of Solar Activity, National Astronomical Observatories, Beijing 100012 (China); Ding, Mingde, E-mail: wangxin@xao.ac.cn [Key Laboratory of Modern Astronomy and Astrophysics (Nanjing University) Ministry of Education, Nanjing 210093 (China)

2017-06-20

Observations by spacecraft such as ACE , STEREO , and others show that there are proton spectral “breaks” with energy E {sub br} at 1–10 MeV in some large CME-driven shocks. Generally, a single shock with the diffusive acceleration mechanism would not predict the “broken” energy spectrum. The present paper focuses on two converging shocks to identify this energy spectral feature. In this case, the converging shocks comprise one forward CME-driven shock on 2006 December 13 and another backward Earth bow shock. We simulate the detailed particle acceleration processes in the region of the converging shocks using the Monte Carlo method. As a result, we not only obtain an extended energy spectrum with an energy “tail” up to a few 10 MeV higher than that in previous single shock model, but also we find an energy spectral “break” occurring on ∼5.5 MeV. The predicted energy spectral shape is consistent with observations from multiple spacecraft. The spectral “break,” then, in this case is caused by the interaction between the CME shock and Earth’s bow shock, and otherwise would not be present if Earth were not in the path of the CME.

Shock waves and rarefaction waves in magnetohydrodynamics. Pt. 1: A model system

International Nuclear Information System (INIS)

Myong, R.S.; Roe, P.L.

1997-01-01

The present study consists of two parts. Here in Part I, a model set of conservation laws exactly preserving the MHD hyperbolic singularities is investigated to develop the general theory of the nonlinear evolution of MHD shock waves. Great emphasis is placed on shock admissibility conditions. By developing the viscosity admissibility condition, it is shown that the intermediate shocks are necessary to ensure that the planar Riemann problem is well-posed. In contrast, it turns out that the evolutionary condition is inappropriate for determining physically relevant MHD, shocks. In the general non-planar case, by studying canonical cases, we show that the solution of the Riemann problem is not necessarily unique - in particular, that it depends not only on reference states but also on the associated internal structure. Finally, the stability of intermediate shocks is discussed, and a theory of their nonlinear evolution is proposed. In Part 2, the theory of nonlinear waves developed for the model is applied to the MHD problem. It is shown that the topology of the MHD Hugoniot and wave curves is identical to that of the model problem. (Author)

Use of Hemadsorption in a Case of Pediatric Toxic Shock Syndrome

Directory of Open Access Journals (Sweden)

Andrea Berkes

2017-01-01

Full Text Available Background. Toxic shock syndrome is a potentially fatal toxin-mediated disease. The role of toxins in this clinical entity made us hypothesize that extracorporeal blood purification with CytoSorb® could play a beneficial role in the clinical management of toxic shock syndrome. This case report describes the successful treatment of toxic shock syndrome using a combination of renal replacement therapy and hemadsorption in a pediatric patient. Case Presentation. A 5-year-old girl with Down’s syndrome presented with an inflamed area surrounding an insect bite, signs of systemic inflammation, and multiple organ failure. As previous attempts of immune modulation therapy were unsuccessful, renal replacement therapy was supplemented by the cytokine absorber CytoSorb. Treatment using this combination was associated with a rapid and significant stabilization in the hemodynamic situation and a decrease in inflammatory mediators within hours after the initiation of therapy. The application of CytoSorb therapy was simple and safe. Conclusion. The use of extracorporeal blood purification with CytoSorb proved potentially beneficial by removing toxins and inflammatory mediators in this case and could therefore play a role in the clinical management of toxic shock syndrome. Whether CytoSorb has the potential to even positively influence mortality in patients with toxic shock syndrome still needs to be confirmed.

Factors That Modulate Neurogenesis: A Top-Down Approach.

Science.gov (United States)

LaDage, Lara D

2016-08-24

Although hippocampal neurogenesis in the adult brain has been conserved across the vertebrate lineage, laboratory studies have primarily examined this phenomenon in rodent models. This approach has been successful in elucidating important factors and mechanisms that can modulate rates of hippocampal neurogenesis, including hormones, environmental complexity, learning and memory, motor stimulation, and stress. However, recent studies have found that neurobiological research on neurogenesis in rodents may not easily translate to, or explain, neurogenesis patterns in nonrodent systems, particularly in species examined in the field. This review examines some of the evolutionary and ecological variables that may also modulate neurogenesis patterns. This 'top-down' and more naturalistic approach, which incorporates ecology and natural history, particularly of nonmodel species, may allow for a more comprehensive understanding of the functional significance of neurogenesis. © 2016 S. Karger AG, Basel.

Bifurcation parameters of a reflected shock wave in cylindrical channels of different roughnesses

Science.gov (United States)

Penyazkov, O.; Skilandz, A.

2018-03-01

To investigate the effect of bifurcation on the induction time in cylindrical shock tubes used for chemical kinetic experiments, one should know the parameters of the bifurcation structure of a reflected shock wave. The dynamics and parameters of the shock wave bifurcation, which are caused by reflected shock wave-boundary layer interactions, are studied experimentally in argon, in air, and in a hydrogen-nitrogen mixture for Mach numbers M = 1.3-3.5 in a 76-mm-diameter shock tube without any ramp. Measurements were taken at a constant gas density behind the reflected shock wave. Over a wide range of experimental conditions, we studied the axial projection of the oblique shock wave and the pressure distribution in the vicinity of the triple Mach configuration at 50, 150, and 250 mm from the endwall, using side-wall schlieren and pressure measurements. Experiments on a polished shock tube and a shock tube with a surface roughness of 20 {μ }m Ra were carried out. The surface roughness was used for initiating small-scale turbulence in the boundary layer behind the incident shock wave. The effect of small-scale turbulence on the homogenization of the transition zone from the laminar to turbulent boundary layer along the shock tube perimeter was assessed, assuming its influence on a subsequent stabilization of the bifurcation structure size versus incident shock wave Mach number, as well as local flow parameters behind the reflected shock wave. The influence of surface roughness on the bifurcation development and pressure fluctuations near the wall, as well as on the Mach number, at which the bifurcation first develops, was analyzed. It was found that even small additional surface roughness can lead to an overshoot in pressure growth by a factor of two, but it can stabilize the bifurcation structure along the shock tube perimeter.

Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

Science.gov (United States)

Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin

2013-08-01

Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Shock wave attenuation in a micro-channel

Science.gov (United States)

Giordano, J.; Perrier, P.; Meister, L.; Brouillette, M.

2018-05-01

This work presents optical measurements of shock wave attenuation in a glass micro-channel. This transparent facility, with a cross section ranging from 1 mm× 150 μm to 1 mm× 500 μm, allowed for the use of high-speed schlieren videography to visualize the propagation of a shock wave within the entire micro-channel and to quantify velocity attenuation of the wave due to wall effects. In this paper, we present the experimental technique and the relevant data treatment we have used to increase the sensitivity of shock wave detection. Then, we compared our experimental results for different channel widths, lengths, and shock wave velocities with the analytical model for shock attenuation proposed by Russell (J Fluid Mech 27(2):305-314, 1967), which assumes laminar flow, and by Mirels (Attenuation in a shock tube due to unsteady-boundary-layer action, NACA Report 1333, 1957) for turbulent flow. We found that these models are inadequate to predict the observed data, owing to the presence of fully developed flow which violates the basic assumption of these models. The data are also compared with the empirical shock attenuation models proposed by Zeitoun (Phys Fluids 27(1):011701, 2015) and Deshpande and Puranik (Shock Waves 26(4):465-475, 2016), where better agreement is observed. Finally, we presented experimental data for the flow field behind the shock wave from measurements of the Mach wave angle which shows globally decreasing flow Mach numbers due to viscous wall effects.

Central venous pressure and shock index predict lack of hemodynamic response to volume expansion in septic shock: a prospective, observational study.

Science.gov (United States)

Lanspa, Michael J; Brown, Samuel M; Hirshberg, Eliotte L; Jones, Jason P; Grissom, Colin K

2012-12-01

Volume expansion is a common therapeutic intervention in septic shock, although patient response to the intervention is difficult to predict. Central venous pressure (CVP) and shock index have been used independently to guide volume expansion, although their use is questionable. We hypothesize that a combination of these measurements will be useful. In a prospective, observational study, patients with early septic shock received 10-mL/kg volume expansion at their treating physician's discretion after brief initial resuscitation in the emergency department. Central venous pressure and shock index were measured before volume expansion interventions. Cardiac index was measured immediately before and after the volume expansion using transthoracic echocardiography. Hemodynamic response was defined as an increase in a cardiac index of 15% or greater. Thirty-four volume expansions were observed in 25 patients. A CVP of 8 mm Hg or greater and a shock index of 1 beat min(-1) mm Hg(-1) or less individually had a good negative predictive value (83% and 88%, respectively). Of 34 volume expansions, the combination of both a high CVP and a low shock index was extremely unlikely to elicit hemodynamic response (negative predictive value, 93%; P = .02). Volume expansion in patients with early septic shock with a CVP of 8 mm Hg or greater and a shock index of 1 beat min(-1) mm Hg(-1) or less is unlikely to lead to an increase in cardiac index. Copyright © 2012 Elsevier Inc. All rights reserved.

Fundamentals of Non-relativistic Collisionless Shock Physics: IV. Quasi-Parallel Supercritical Shocks

OpenAIRE

Treumann, R. A.; Jaroschek, C. H.

2008-01-01

1. Introduction, 2. The (quasi-parallel) foreshock; Ion foreshock, Ion foreshock boundary region; Diffuse ions;Low-frequency upstream waves; Ion beam waves; The expected wave modes; Observations; Diffuse ion waves; Electron foreshock; Electron beams; Langmuir waves; stability of the electron beam; Electron foreshock boundary waves; Nature of electron foreshock waves; Radiation; Observations; Interpretation; 3. Quasi-parallel shock reformation; Low-Mach number quasi-parallel shocks; Turbulent ...

Three-dimensional simulations of core-collapse supernovae: from shock revival to shock breakout

Science.gov (United States)

Wongwathanarat, A.; Müller, E.; Janka, H.-Th.

2015-05-01

We present three-dimensional hydrodynamic simulations of the evolution of core-collapse supernovae (SN) from blast-wave initiation by the neutrino-driven mechanism to shock breakout from the stellar surface, using an axis-free Yin-Yang grid and considering two 15 M⊙ red supergiants (RSG) and two blue supergiants (BSG) of 15 M⊙ and 20 M⊙. We demonstrate that the metal-rich ejecta in homologous expansion still carry fingerprints of asymmetries at the beginning of the explosion, but the final metal distribution is massively affected by the detailed progenitor structure. The most extended and fastest metal fingers and clumps are correlated with the biggest and fastest-rising plumes of neutrino-heated matter, because these plumes most effectively seed the growth of Rayleigh-Taylor (RT) instabilities at the C+O/He and He/H composition-shell interfaces after the passage of the SN shock. The extent of radial mixing, global asymmetry of the metal-rich ejecta, RT-induced fragmentation of initial plumes to smaller-scale fingers, and maximum Ni and minimum H velocities depend not only on the initial asphericity and explosion energy (which determine the shock and initial Ni velocities), but also on the density profiles and widths of C+O core and He shell and on the density gradient at the He/H transition, which leads to unsteady shock propagation and the formation of reverse shocks. Both RSG explosions retain a large global metal asymmetry with pronounced clumpiness and substructure, deep penetration of Ni fingers into the H-envelope (with maximum velocities of 4000-5000 km s-1 for an explosion energy around 1.5 bethe) and efficient inward H-mixing. While the 15 M⊙ BSG shares these properties (maximum Ni speeds up to ~3500 km s-1), the 20 M⊙ BSG develops a much more roundish geometry without pronounced metal fingers (maximum Ni velocities only ~2200 km s-1) because of reverse-shock deceleration and insufficient time for strong RT growth and fragmentation at the He

Clinical features and risk factors for severe and critical pregnant women with 2009 pandemic H1N1 influenza infection in China

Directory of Open Access Journals (Sweden)

Zhang Peng-jun

2012-02-01

Full Text Available Abstract Background 2009 pandemic H1N1 (pH1N1 influenza posed an increased risk of severe illness among pregnant women. Data on risk factors associated with death of pregnant women and neonates with pH1N1 infections are limited outside of developed countries. Methods Retrospective observational study in 394 severe or critical pregnant women admitted to a hospital with pH1N1 influenza from Sep. 1, 2009 to Dec. 31, 2009. rRT-PCR testing was used to confirm infection. In-hospital mortality was the primary endpoint of this study. Univariable logistic analysis and multivariate logistic regression analysis were used to investigate the potential factors on admission that might be associated with the maternal and neonatal mortality. Results 394 pregnant women were included, 286 were infected with pH1N1 in the third trimester. 351 had pneumonia, and 77 died. A PaO2/FiO2 ≤ 200 (odds ratio (OR, 27.16; 95% confidence interval (CI, 2.64-279.70 and higher BMI (i.e. ≥ 30 on admission (OR, 1.26; 95% CI, 1.09 to 1.47 were independent risk factors for maternal death. Of 211 deliveries, 146 neonates survived. Premature delivery (OR, 4.17; 95% CI, 1.19-14.56 was associated neonatal mortality. Among 186 patients who received mechanical ventilation, 83 patients were treated with non-invasive ventilation (NIV and 38 were successful with NIV. The death rate was lower among patients who initially received NIV than those who were initially intubated (24/83, 28.9% vs 43/87, 49.4%; p = 0.006. Septic shock was an independent risk factor for failure of NIV. Conclusions Severe hypoxemia and higher BMI on admission were associated with adverse outcomes for pregnant women. Preterm delivery was a risk factor for neonatal death among pregnant women with pH1N1 influenza infection. NIV may be useful in selected pregnant women without septic shock.

Impact of Shock Front Rippling and Self-reformation on the Electron Dynamics at Low-Mach-number Shocks

Science.gov (United States)

Yang, Zhongwei; Lu, Quanming; Liu, Ying D.; Wang, Rui

2018-04-01

Electron dynamics at low-Mach-number collisionless shocks are investigated by using two-dimensional electromagnetic particle-in-cell simulations with various shock normal angles. We found: (1) The reflected ions and incident electrons at the shock front provide an effective mechanism for the quasi-electrostatic wave generation due to the charge-separation. A fraction of incident electrons can be effectively trapped and accelerated at the leading edge of the shock foot. (2) At quasi-perpendicular shocks, the electron trapping and reflection is nonuniform due to the shock rippling along the shock surface and is more likely to take place at some locations accompanied by intense reflected ion-beams. The electron trapping process has a periodical evolution over time due to the shock front self-reformation, which is controlled by ion dynamics. Thus, this is a cross-scale coupling phenomenon. (3) At quasi-parallel shocks, reflected ions can travel far back upstream. Consequently, quasi-electrostatic waves can be excited in the shock transition and the foreshock region. The electron trajectory analysis shows these waves can trap electrons at the foot region and reflect a fraction of them far back upstream. Simulation runs in this paper indicate that the micro-turbulence at the shock foot can provide a possible scenario for producing the reflected electron beam, which is a basic condition for the type II radio burst emission at low-Mach-number interplanetary shocks driven by Coronal Mass Ejections (CMEs).

Psychometric evaluation of the Environmental Reality Shock-Related Issues and Concerns instrument for newly graduated nurses.

Science.gov (United States)

Kim, Eun-Young; Yeo, Jung Hee; Park, Hyunjeong; Sin, Kyung Mi; Jones, Cheryl B

2018-02-01

Reality shock is a critical representation of the gap between nursing education and clinical practice and it is important to explore the level of reality shock among nurses. However, there is no relevant instrument to assess the level of reality shock in South Korea. The purpose of this is to determine the validity and reliability of the Korean version of the Environmental Reality Shock-Related Issues and Concerns instrument. A cross-sectional study design was used in this study. The data collection was conducted in selected 15 hospitals in South Korea. A convenience sample of 216 newly graduated nurses participated in the study. The Korean version of the Environmental Reality Shock-Related Issues and Concerns instrument was developed through the forward-backward translation technique, and revision based on feedback from expert groups. The internal consistency reliability was assessed using Cronbach's alpha, and the construct validity was determined via exploratory and confirmatory factor analysis. The Korean version of the Environmental Reality Shock-Related Issues and Concerns has reliable internal consistency (Cronbach's alpha=0.91). Exploratory factor analysis revealed five factors including job, relationships, expectations, private life, and performance, which explained 61.92% of variance. The factor loadings ranged from 0.451 to 0.832. The five-factor structure was validated by confirmatory factor analysis (RMR0.9). It was concluded that the Korean version of the Environmental Reality Shock-Related Issues and Concerns instrument has satisfactory construct validity and reliability to measure the reality shock of newly graduated nurses in South Korea. Copyright © 2017 Elsevier Ltd. All rights reserved.

GNC and CGA1 Modulate Chlorophyll Biosynthesis and Glutamate Synthase (GLU1/Fd-GOGAT) Expression in Arabidopsis

Science.gov (United States)

Hudson, Darryl; Guevara, David; Yaish, Mahmoud W.; Hannam, Carol; Long, Nykoll; Clarke, Joseph D.; Bi, Yong-Mei; Rothstein, Steven J.

2011-01-01

Chloroplast development is an important determinant of plant productivity and is controlled by environmental factors including amounts of light and nitrogen as well as internal phytohormones including cytokinins and gibberellins (GA). The paralog GATA transcription factors GNC and CGA1/GNL up-regulated by light, nitrogen and cytokinin while also being repressed by GA signaling. Modifying the expression of these genes has previously been shown to influence chlorophyll content in Arabidopsis while also altering aspects of germination, elongation growth and flowering time. In this work, we also use transgenic lines to demonstrate that GNC and CGA1 exhibit a partially redundant control over chlorophyll biosynthesis. We provide novel evidence that GNC and CGA1 influence both chloroplast number and leaf starch in proportion to their transcript level. GNC and CGA1 were found to modify the expression of chloroplast localized GLUTAMATE SYNTHASE (GLU1/Fd-GOGAT), which is the primary factor controlling nitrogen assimilation in green tissue. Altering GNC and CGA1 expression was also found to modulate the expression of important chlorophyll biosynthesis genes (GUN4, HEMA1, PORB, and PORC). As previously demonstrated, the CGA1 transgenic plants demonstrated significantly altered timing to a number of developmental events including germination, leaf production, flowering time and senescence. In contrast, the GNC transgenic lines we analyzed maintain relatively normal growth phenotypes outside of differences in chloroplast development. Despite some evidence for partial divergence, results indicate that regulation of both GNC and CGA1 by light, nitrogen, cytokinin, and GA acts to modulate nitrogen assimilation, chloroplast development and starch production. Understanding the mechanisms controlling these processes is important for agricultural biotechnology. PMID:22102866

demystifying the shock of shocking

African Journals Online (AJOL)

(with a pulse), atrial fibrillation and atrial flutter. The energy dose in cardioversion is less (0.5. - 2 J/kg) than in defibrillation (2 - 4 J/kg). In cardioversion the shock is discharged synchronously with the native R wave of the patient. Without synchronisation,. VF can be induced if a shock is delivered during the refractory period ...

Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays

Directory of Open Access Journals (Sweden)

Regina Augustin

2011-01-01

Full Text Available The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases.

INJECTION TO RAPID DIFFUSIVE SHOCK ACCELERATION AT PERPENDICULAR SHOCKS IN PARTIALLY IONIZED PLASMAS

Energy Technology Data Exchange (ETDEWEB)

Ohira, Yutaka, E-mail: ohira@phys.aoyama.ac.jp [Department of Physics and Mathematics, Aoyama Gakuin University, 5-10-1 Fuchinobe, Sagamihara 252-5258 (Japan)

2016-08-10

We present a three-dimensional hybrid simulation of a collisionless perpendicular shock in a partially ionized plasma for the first time. In this simulation, the shock velocity and upstream ionization fraction are v {sub sh} ≈ 1333 km s{sup −1} and f {sub i} ∼ 0.5, which are typical values for isolated young supernova remnants (SNRs) in the interstellar medium. We confirm previous two-dimensional simulation results showing that downstream hydrogen atoms leak into the upstream region and are accelerated by the pickup process in the upstream region, and large magnetic field fluctuations are generated both in the upstream and downstream regions. In addition, we find that the magnetic field fluctuations have three-dimensional structures and the leaking hydrogen atoms are injected into the diffusive shock acceleration (DSA) at the perpendicular shock after the pickup process. The observed DSA can be interpreted as shock drift acceleration with scattering. In this simulation, particles are accelerated to v ∼ 100 v {sub sh} ∼ 0.3 c within ∼100 gyroperiods. The acceleration timescale is faster than that of DSA in parallel shocks. Our simulation results suggest that SNRs can accelerate cosmic rays to 10{sup 15.5} eV (the knee) during the Sedov phase.

Shock absorbing structure

International Nuclear Information System (INIS)

Kojima, Naoki; Matsushita, Kazuo.

1992-01-01

Small pieces of shock absorbers are filled in a space of a shock absorbing vessel which is divided into a plurality of sections by partitioning members. These sections function to prevent excess deformation or replacement of the fillers upon occurrence of falling accident. Since the shock absorbing small pieces in the shock absorbing vessel are filled irregularly, shock absorbing characteristics such as compression strength is not varied depending on the direction, but they exhibit excellent shock absorbing performance. They surely absorb shocks exerted on a transportation vessel upon falling or the like. If existing artificial fillers such as pole rings made of metal or ceramic and cut pieces such as alumium extrusion molding products are used as the shock absorbing pieces, they have excellent fire-proofness and cold resistance since the small pieces are inflammable and do not contain water. (T.M.)

Energy shocks and detecting influential industries

International Nuclear Information System (INIS)

Kang, Dongsuk; Lee, Duk Hee

2017-01-01

An industry's relationship of supply and demand with the energy sector can be a critical factor in the stability of its economic performance. Furthermore, the patterns of industry dependence on energy industries can be a major characteristic of entire industrial structure. This research evaluates industries' impact scores for their overall influence on other industries and vulnerability to supply and demand shocks from the energy sector. The study utilizes a sample of Korea's industrial input–output tables from 2010 to 2012. Using a chain of complementary methodologies, this study finds that among four clusters, energy, services, and raw materials are key members that can spread energy shocks to other industries. Therefore, governments need to prepare effective energy efficiency policies for these target industries. - Highlights: • We analyze an industry's impact score of its vulnerability to energy shock and inter-industrial effects. • We utilize the sample of input-output tables in Korea from 2010 to 2012. • We implement simulation, PCA, TOPSIS, cluster analysis about energy shock and industrial trades. • Subsectors of energy, services, raw material are subject to energy shock and influential to others. • These bridge industries can be targets that require policies for effective energy efficiency.

Studies on laser–plasma interaction physics for shock ignition

Czech Academy of Sciences Publication Activity Database

Maheut, Y.; Batani, D.; Nicolai, Ph.; Antonelli, L.; Krouský, Eduard

2015-01-01

Roč. 170, č. 4 (2015), s. 325-336 ISSN 1042-0150 EU Projects: European Commission(XE) 284464 - LASERLAB-EUROPE Institutional support: RVO:68378271 Keywords : shock ignition * plasma * hot electrons * shocks * fusion Subject RIV: BL - Plasma and Gas Discharge Physics OBOR OECD: Fluids and plasma physics (including surface physics) Impact factor: 0.472, year: 2015

Radiative shocks with electron thermal conduction

International Nuclear Information System (INIS)

Borkowski, Kazimierz.

1988-01-01

The authors studies the influence of electron thermal conduction on radiative shock structure for both one- and two-temperature plasmas. The dimensionless ratio of the conductive length to the cooling length determines whether or not conduction is important, and shock jump conditions with conduction are established for a collisionless shock front. He obtains approximate solutions with the assumptions that the ionization state of the gas is constant and the cooling rate is a function of temperature alone. In the absence of magnetic fields, these solutions indicate that conduction noticeably influences normal-abundance interstellar shocks with velocities 50-100 km s -1 and dramatically affects metal-dominated shocks over a wide range of shock velocities. Magnetic fields inhibit conduction, but the conductive energy flux and the corresponding decrease in the post-shock electron temperature may still be appreciable. He calculates detailed steady-state radiative shock models in gas composed entirely of oxygen, with the purpose of explaining observations of fast-moving knots in Cas A and other oxygen-rich supernova remnants (SNRs). The O III ion, whose forbidden emission usually dominates the observed spectra, is present over a wide range of shock velocities, from 100 to 170 kms -1 . All models with conduction have extensive warm photoionization zones, which provides better agreement with observed optical (O I) line strengths. However, the temperatures in these zones could be lowered by (Si II) 34.8 μm and (Ne II) 12.8 μm cooling if Si and Ne are present in appreciable abundance relative to O. Such low temperatures would be inconsistent with the observed (O I) emission in oxygen-rich SNRs

Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

Directory of Open Access Journals (Sweden)

Narsing A Rao

Full Text Available The small heat shock protein, αA-crystallin null (αA-/- mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU. In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB, a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice, which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ, both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

Science.gov (United States)

Rao, Narsing A; Saraswathy, Sindhu; Pararajasegaram, Geeta; Bhat, Suraj P

2012-01-01

The small heat shock protein, αA-crystallin null (αA-/-) mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice), which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ), both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

Nonstationarity of a two-dimensional perpendicular shock: Competing mechanisms

Czech Academy of Sciences Publication Activity Database

Lembège, B.; Savoini, P.; Hellinger, Petr; Trávníček, Pavel M.

2009-01-01

Roč. 114, A03217 (2009), A03217/1-A03217/21 ISSN 0148-0227 R&D Pro jects: GA AV ČR IAA300420702; GA AV ČR IAA300420602 Institutional research plan: CEZ:AV0Z30420517 Keywords : Collisionless shocks * self-reformation * nonlinear waves Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 3.082, year: 2009

Study on Reflected Shock Wave/Boundary Layer Interaction in a Shock Tube

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Wook; Kim, Tae Ho; Kim, Heuy Dong [Andong Nat’l Univ., Andong (Korea, Republic of)

2017-07-15

The interaction between a shock wave and a boundary layer causes boundary layer separation, shock train, and in some cases, strong unsteadiness in the flow field. Such a situation is also observed in a shock tube, where the reflected shock wave interacts with the unsteady boundary layer. However, only a few studies have been conducted to investigate the shock train phenomenon in a shock tube. In the present study, numerical studies were conducted using the two-dimensional axisymmetric domain of a shock tube, and compressible Navier-Stokes equations were solved to clarify the flow characteristics of shock train phenomenon inside a shock tube. A detailed wave diagram was developed based on the present computational results, which were validated with existing experimental data.

Role of immune system modulation in prevention of type 1 diabetes mellitus

Directory of Open Access Journals (Sweden)

Gamal Abdulrhman Hassan

2012-01-01

Full Text Available An increased incidence of Type 1 diabetes mellitus (T1DM is expected worldwide. Eventually, T1DM is fatal unless treated with insulin. The expansion of interventions to prevent diabetes and the use of alternative treatments to insulin is a dream to be fulfilled. The pathophysiology in T1DM is basically a destruction of beta cells in the pancreas, regardless of which risk factors or causative entities have been present. Individual risk factors can have separate patho-physiological processes to, in turn, cause this beta cell destruction. Currently, autoimmunity is considered the major factor in the pathophysiology of T1DM. In a genetically susceptible individual, viral infection may stimulate the production of antibodies against a viral protein that trigger an autoimmune response against antigenically similar beta cell molecules. Many components of the immune system have been implicated in autoimmunity leading to β-cell destruction, including cytotoxic and helper T-cells, B-cells, macrophages, and dendritic cells. The inflammatory process in early diabetes is thought to be initiated and propagated by the effect of Th1-secreted cytokines (e.g. g interferon and suppressed by Th2-secreted antiinflammatory cytokines (interleukins. Structure and function of β-cell may be modulated by using Th1/Th2-secreted cytokines. Several experimental and clinical trials of applying GAD65, Hsp60, peptide-MHC, pepetide-277 immunization, anti-CD3 infusion, and interleukins to modulate immune response in T1DM were done. Applying such trials in patients with prediabetes, will most likely be the future key in preventing Type 1 autoimmune diabetes.

[Analysis of risk factors of fatal outcome in pregnant and puerperant patients with severe H1N1 influenza].

Science.gov (United States)

Zabolotskikh, I B; Penzhoian, G A; Musaeva, T S; Goncharenko, S I

2010-01-01

As well as previous epidemics and pandemias of influenza, the 2009 H1N1 influenza pandemia increases the risk of severe illness in pregnant. Data were reported for 28 pregnant and 2 postpartum women who have been hospitalized in ICUs of Krasnodar Region with H1N1 influenza diagnosis. The laboratory tests for H1N1 were negative in 53.3% of suspected cases of H1N1 influenza (16 of 30). The major lethal risk factor in pregnant with H1N1 influenza is a development of septic shock with low PaO2\\FiO2 ratio (less than 140) and high Murray's Acute Lung Injury Score (higher than 2.5). High Apache II, Apache III, SAPS 2, SAPS 3 and SOFA scores are the additional lethal risk factors. Lethal outcomes were more frequent in the end of the second trimester of pregnancy.

Recent results from experimental studies on laser-plasma coupling in a shock ignition relevant regime

Czech Academy of Sciences Publication Activity Database

Koester, P.; Antonelli, L.; Atzeni, S.; Badziak, J.; Baffigi, F.; Batani, D.; Cecchetti, C.A.; Chodukowski, T.; Consoli, F.; Cristoforetti, G.; De Angelis, R.; Folpini, G.; Gizzi, L.A.; Kalinowska, Z.; Krouský, Eduard; Kuchařík, M.; Labate, L.; Levato, T.; Liška, R.; Malka, G.; Maheut, Y.; Marocchino, A.; Nicolai, P.; O´Dell, T.; Parys, P.; Pisarczyk, T.; Rączka, P.; Renner, Oldřich; Rhee, Y.-J.; Ribeyre, X.; Richetta, M.; Rosinski, M.; Ryc, L.; Skála, Jiří; Schiavi, A.; Schurtz, G.; Šmíd, Michal; Spindloe, C.; Ullschmied, Jiří; Wolowski, J.; Zaras, A.

2013-01-01

Roč. 55, č. 12 (2013), , "124045-1"-"124045-8" ISSN 0741-3335 R&D Projects: GA MŠk(CZ) LC528; GA MŠk LM2010014 EU Projects: European Commission(XE) 284464 - LASERLAB-EUROPE Institutional support: RVO:68378271 ; RVO:61389021 Keywords : laser-produced plasma s * inertial confinement fusion * shock ignition * X-ray imaging spectroscopy * ion diagnostics * interferometry * shock breakout chron Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 2.386, year: 2013

CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro