Inhibiting connexin channels protects against cryopreservation-induced cell death in human blood vessels.

PubMed

Bol, M; Van Geyt, C; Baert, S; Decrock, E; Wang, N; De Bock, M; Gadicherla, A K; Randon, C; Evans, W H; Beele, H; Cornelissen, R; Leybaert, L

2013-04-01

Cryopreserved blood vessels are being increasingly employed in vascular reconstruction procedures but freezing/thawing is associated with significant cell death that may lead to graft failure. Vascular cells express connexin proteins that form gap junction channels and hemichannels. Gap junction channels directly connect the cytoplasm of adjacent cells and may facilitate the passage of cell death messengers leading to bystander cell death. Two hemichannels form a gap junction channel but these channels are also present as free non-connected hemichannels. Hemichannels are normally closed but may open under stressful conditions and thereby promote cell death. We here investigated whether blocking gap junctions and hemichannels could prevent cell death after cryopreservation. Inclusion of Gap27, a connexin channel inhibitory peptide, during cryopreservation and thawing of human saphenous veins and femoral arteries was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays and histological examination. We report that Gap27 significantly reduces cell death in human femoral arteries and saphenous veins when present during cryopreservation/thawing. In particular, smooth muscle cell death was reduced by 73% in arteries and 71% in veins, while endothelial cell death was reduced by 32% in arteries and 51% in veins. We conclude that inhibiting connexin channels during cryopreservation strongly promotes vascular cell viability. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits

PubMed Central

Meigh, Louise; Greenhalgh, Sophie A; Rodgers, Thomas L; Cann, Martin J; Roper, David I; Dale, Nicholas

2013-01-01

Homeostatic regulation of the partial pressure of CO2 (PCO2) is vital for life. Sensing of pH has been proposed as a sufficient proxy for determination of PCO2 and direct CO2-sensing largely discounted. Here we show that connexin 26 (Cx26) hemichannels, causally linked to respiratory chemosensitivity, are directly modulated by CO2. A ‘carbamylation motif’, present in CO2-sensitive connexins (Cx26, Cx30, Cx32) but absent from a CO2-insensitive connexin (Cx31), comprises Lys125 and four further amino acids that orient Lys125 towards Arg104 of the adjacent subunit of the connexin hexamer. Introducing the carbamylation motif into Cx31 created a mutant hemichannel (mCx31) that was opened by increases in PCO2. Mutation of the carbamylation motif in Cx26 and mCx31 destroyed CO2 sensitivity. Course-grained computational modelling of Cx26 demonstrated that the proposed carbamate bridge between Lys125 and Arg104 biases the hemichannel to the open state. Carbamylation of Cx26 introduces a new transduction principle for physiological sensing of CO2. DOI: http://dx.doi.org/10.7554/eLife.01213.001 PMID:24220509

Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease

PubMed Central

Hadjihambi, Anna; De Chiara, Francesco; Hosford, Patrick S.; Habtetion, Abeba; Karagiannis, Anastassios; Davies, Nathan

2017-01-01

The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and ammonia is thought to play a key role. Astroglial dysfunction is known to be present in HE. Astrocytes are extensively connected by gap junctions formed of connexins, which also exist as functional hemichannels allowing exchange of molecules between the cytoplasm and the extracellular milieu. The astrocyte‐neuron lactate shuttle hypothesis suggests that neuronal activity is fueled (at least in part) by lactate provided by neighboring astrocytes. We hypothesized that in HE, astroglial dysfunction could impair metabolic communication between astrocytes and neurons. In this study, we determined whether hyperammonemia leads to hemichannel dysfunction and impairs lactate transport in the cerebral cortex using rat models of HE (bile duct ligation [BDL] and induced hyperammonemia) and also evaluated the effect of ammonia‐lowering treatment (ornithine phenylacetate [OP]). Plasma ammonia concentration in BDL rats was significantly reduced by OP treatment. Biosensor recordings demonstrated that HE is associated with a significant reduction in both tonic and hypoxia‐induced lactate release in the cerebral cortex, which was normalized by OP treatment. Cortical dye loading experiments revealed hemichannel dysfunction in HE with improvement following OP treatment, while the expression of key connexins was unaffected. Conclusion: The results of the present study demonstrate that HE is associated with central nervous system hemichannel dysfunction, with ammonia playing a key role. The data provide evidence of a potential neuronal energy deficit due to impaired hemichannel‐mediated lactate transport between astrocytes and neurons as a possible mechanism underlying pathogenesis of HE. (Hepatology 2017;65:1306‐1318) PMID:28066916

Three-dimensional wax patterning of paper fluidic devices.

PubMed

Renault, Christophe; Koehne, Jessica; Ricco, Antonio J; Crooks, Richard M

2014-06-17

In this paper we describe a method for three-dimensional wax patterning of microfluidic paper-based analytical devices (μPADs). The method is rooted in the fundamental details of wax transport in paper and provides a simple way to fabricate complex channel architectures such as hemichannels and fully enclosed channels. We show that three-dimensional μPADs can be fabricated with half as much paper by using hemichannels rather than ordinary open channels. We also provide evidence that fully enclosed channels are efficiently isolated from the exterior environment, decreasing contamination risks, simplifying the handling of the device, and slowing evaporation of solvents.

Currently used methods for identification and characterization of hemichannels.

PubMed

Schalper, Kurt A; Palacios-Prado, Nicolás; Orellana, Juan A; Sáez, Juan C

2008-05-01

Connexins and pannexins are vertebrate transmembrane proteins that form hexameric conduits termed hemichannels. Functional hemichannels allow the diffusional transport of ions and small molecules across the plasma membrane and serve as paracrine and autocrine communication pathways. During the last decade, interest in the hemichannel field increased substantially. Today, there is evidence for the existence of connexin hemichannels in vertebrate cells and bulk of information supports their function in diverse physiological and pathological responses. Controversy regarding the molecular identity of the hemichannel type mediating many responses arose recently with the identification of pannexin-based hemichannels. Here, the authors describe the most frequently used methods for studying hemichannels in living mammalian cells and focus on those with which they have more experience. Although the available in vitro evidence is substantial, further studies and possibly new experimental approaches are required to understand the role and properties of connexin and pannexin hemichannels in vivo.

The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels.

PubMed

Riquelme, Manuel A; Cea, Luis A; Vega, José L; Boric, Mauricio P; Monyer, Hannah; Bennett, Michael V L; Frank, Marina; Willecke, Klaus; Sáez, Juan C

2013-12-01

During repetitive stimulation of skeletal muscle, extracellular ATP levels raise, activating purinergic receptors, increasing Ca2+ influx, and enhancing contractile force, a response called potentiation. We found that ATP appears to be released through pannexin1 hemichannels (Panx1 HCs). Immunocytochemical analyses and function were consistent with pannexin1 localization to T-tubules intercalated with dihydropyridine and ryanodine receptors in slow (soleus) and fast (extensor digitorum longus, EDL) muscles. Isolated myofibers took up ethidium (Etd+) and released small molecules (as ATP) during electrical stimulation. Consistent with two glucose uptake pathways, induced uptake of 2-NBDG, a fluorescent glucose derivative, was decreased by inhibition of HCs or glucose transporter (GLUT4), and blocked by dual blockade. Adult skeletal muscles apparently do not express connexins, making it unlikely that connexin hemichannels contribute to the uptake and release of small molecules. ATP release, Etd+ uptake, and potentiation induced by repetitive electrical stimulation were blocked by HC blockers and did not occur in muscles of pannexin1 knockout mice. MRS2179, a P2Y1R blocker, prevented potentiation in EDL, but not soleus muscles, suggesting that in fast muscles ATP activates P2Y1 but not P2X receptors. Phosphorylation on Ser and Thr residues of pannexin1 was increased during potentiation, possibly mediating HC opening. Opening of Panx1 HCs during repetitive activation allows efflux of ATP, influx of glucose and possibly Ca2+ too, which are required for potentiation of contraction. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuron-Glia Crosstalk in the Autonomic Nervous System and Its Possible Role in the Progression of Metabolic Syndrome: A New Hypothesis

PubMed Central

Del Rio, Rodrigo; Quintanilla, Rodrigo A.; Orellana, Juan A.; Retamal, Mauricio A.

2015-01-01

Metabolic syndrome (MS) is characterized by the following physiological alterations: increase in abdominal fat, insulin resistance, high concentration of triglycerides, low levels of HDL, high blood pressure, and a generalized inflammatory state. One of the pathophysiological hallmarks of this syndrome is the presence of neurohumoral activation, which involve autonomic imbalance associated to hyperactivation of the sympathetic nervous system. Indeed, enhanced sympathetic drive has been linked to the development of endothelial dysfunction, hypertension, stroke, myocardial infarct, and obstructive sleep apnea. Glial cells, the most abundant cells in the central nervous system, control synaptic transmission, and regulate neuronal function by releasing bioactive molecules called gliotransmitters. Recently, a new family of plasma membrane channels called hemichannels has been described to allow the release of gliotransmitters and modulate neuronal firing rate. Moreover, a growing amount of evidence indicates that uncontrolled hemichannel opening could impair glial cell functions, affecting synaptic transmission and neuronal survival. Given that glial cell functions are disturbed in various metabolic diseases, we hypothesize that progression of MS may relies on hemichannel-dependent impairment of glial-to-neuron communication by a mechanism related to dysfunction of inflammatory response and mitochondrial metabolism of glial cells. In this manuscript, we discuss how glial cells may contribute to the enhanced sympathetic drive observed in MS, and shed light about the possible role of hemichannels in this process. PMID:26648871

Characterization of Nonjunctional Hemichannels in Caterpillar Cells

PubMed Central

Luo, Kaijun; Turnbull, Matthew W.

2011-01-01

Recent studies have demonstrated that hemichannels, which form gap junctions when paired from apposing cells, may serve additional roles when unpaired including cell adhesion and paracrine communication. Hemichannels in mammals are formed by connexins or pannexins, while in insects they are formed by pannexin homologues termed innexins. The formation of functional gap junctions by insect innexins has been established, although their ability to form functional nonjunctional hemichannels has not been reported. Here the characteristics of nonjunctional hemichannels were examined in three lepidopteran cell types, two cell lines (High Five and Sf9) and explanted hemocytes from Heliothis virescens (Fabricius) (Lepidoptera: Noctuidae). Selective fluorescent dye uptake by hemichannels was observed in a significant minority of cells, using fluorescence microscopy and flow cytometry. Carbenoxelone, an inhibitor of mammalian junctions, disrupted dye uptake, while flufenamic acid and mefloquine did not. The presence of Ca2+ and Mg2+ in the media increased hemichannel activity. Additionally, lipopolysaccharide, a stimulator of immune activity in lepidopterans, decreased dye uptake. These results demonstrate for the first time the activity of nonjunctional hemichannels in insect cells, as well as pharmacological tools to manipulate them. These results will facilitate the further examination of the role of innexins and nonjunctional hemichannels in insect cell biology, including paracrine signaling, and comparative studies of mammalian pannexins and insect innexins. PMID:21521140

Possible role of hemichannels in cancer

PubMed Central

Schalper, Kurt A.; Carvajal-Hausdorf, Daniel; Oyarzo, Mauricio P.

2014-01-01

In humans, connexins (Cxs) and pannexins (Panxs) are the building blocks of hemichannels. These proteins are frequently altered in neoplastic cells and have traditionally been considered as tumor suppressors. Alteration of Cxs and Panxs in cancer cells can be due to genetic, epigenetic and post-transcriptional/post-translational events. Activated hemichannels mediate the diffusional membrane transport of ions and small signaling molecules. In the last decade hemichannels have been shown to participate in diverse cell processes including the modulation of cell proliferation and survival. However, their possible role in tumor growth and expansion remains largely unexplored. Herein, we hypothesize about the possible role of hemichannels in carcinogenesis and tumor progression. To support this theory, we summarize the evidence regarding the involvement of hemichannels in cell proliferation and migration, as well as their possible role in the anti-tumor immune responses. In addition, we discuss the evidence linking hemichannels with cancer in diverse models and comment on the current technical limitations for their study. PMID:25018732

The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

PubMed Central

Basilio, Daniel; Sáez, Juan C.; Orellana, Juan A.; Raine, Cedric S.; Bukauskas, Feliksas; Bennett, Michael V. L.; Berman, Joan W.

2013-01-01

Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system. PMID:22438035

Glial hemichannels and their involvement in aging and neurodegenerative diseases.

PubMed

Orellana, Juan A; von Bernhardi, Rommy; Giaume, Christian; Sáez, Juan C

2012-01-26

During the last two decades, it became increasingly evident that glial cells accomplish a more important role in brain function than previously thought. Glial cells express pannexins and connexins, which are member subunits of two protein families that form membrane channels termed hemichannels. These channels communicate intra- and extracellular compartments and allow the release of autocrine/paracrine signaling molecules [e.g., adenosine triphosphate (ATP), glutamate, nicotinamide adenine dinucleotide, and prostaglandin E2] to the extracellular milieu, as well as the uptake of small molecules (e.g., glucose). An increasing body of evidence has situated glial hemichannels as potential regulators of the beginning and maintenance of homeostatic imbalances observed in diverse brain diseases. Here, we review and discuss the current evidence about the possible role of glial hemichannels on neurodegenerative diseases. A subthreshold pathological threatening condition leads to microglial activation, which keeps active defense and restores the normal function of the central nervous system. However, if the stimulus is deleterious, microglial cells and the endothelium become overactivated, both releasing bioactive molecules (e.g., glutamate, cytokines, prostaglandins, and ATP), which increase the activity of glial hemichannels, reducing the astroglial neuroprotective functions, and further reducing neuronal viability. Because ATP and glutamate are released via glial hemichannels in neurodegenerative conditions, it is expected that they contribute to neurotoxicity. More importantly, toxic molecules released via glial hemichannels could increase the Ca2+ entry in neurons also via neuronal hemichannels, leading to neuronal death. Therefore, blockade of hemichannels expressed by glial cells and/or neurons during neuroinflammation might prevent neurodegeneration.

General anesthetics have differential inhibitory effects on gap junction channels and hemichannels in astrocytes and neurons.

PubMed

Liu, Xinhe; Gangoso, Ester; Yi, Chenju; Jeanson, Tiffany; Kandelman, Stanislas; Mantz, Jean; Giaume, Christian

2016-04-01

Astrocytes represent a major non-neuronal cell population actively involved in brain functions and pathologies. They express a large amount of gap junction proteins that allow communication between adjacent glial cells and the formation of glial networks. In addition, these membrane proteins can also operate as hemichannels, through which "gliotransmitters" are released, and thus contribute to neuroglial interaction. There are now reports demonstrating that alterations of astroglial gap junction communication and/or hemichannel activity impact neuronal and synaptic activity. Two decades ago we reported that several general anesthetics inhibited gap junctions in primary cultures of astrocytes (Mantz et al., (1993) Anesthesiology 78(5):892-901). As there are increasing studies investigating neuroglial interactions in anesthetized mice, we here updated this previous study by employing acute cortical slices and by characterizing the effects of general anesthetics on both astroglial gap junctions and hemichannels. As hemichannel activity is not detected in cortical astrocytes under basal conditions, we treated acute slices with the endotoxin LPS or proinflammatory cytokines to induce hemichannel activity in astrocytes, which in turn activated neuronal hemichannels. We studied two extensively used anesthetics, propofol and ketamine, and the more recently developed dexmedetomidine. We report that these drugs have differential inhibitory effects on gap junctional communication and hemichannel activity in astrocytes when used in their respective, clinically relevant concentrations, and that dexmedetomidine appears to be the least effective on both channel functions. In addition, the three anesthetics have similar effects on neuronal hemichannels. Altogether, our observations may contribute to optimizing the selection of anesthetics for in vivo animal studies. © 2015 Wiley Periodicals, Inc.

N-TERMINALLY ELONGATED SpliInx2 AND SpliInx3 REDUCE BACULOVIRUS-TRIGGERED APOPTOSIS VIA HEMICHANNEL CLOSURE.

PubMed

Chen, Ya-Bin; Xiao, Wei; Li, Ming; Zhang, Yan; Yang, Yang; Hu, Jian-Sheng; Luo, Kai-Jun

2016-05-01

The hemichannel and gap junction channel are major portals for the release of factors responsible for the effects of apoptotic cells on the spread of apoptosis to neighboring cells and apoptotic corpse clearance, typically by phagocytes. The N-terminal cytoplasmic domain in the connexins, gap junction proteins in vertebrate, has been implicated in regulating channel closure. However, little is known about how the hemichannel close responds to apoptotic signaling transduction leading to the reduction of neighboring cellular apoptosis in an invertebrate. An insect Bac-to-Bac expression system, pFastBac(TM) HT A, allows us to construct an N-terminally elongated SpliInx2 (Nte-Inx2) and SpliInx3 (Nte-Inx3). Here, we demonstrated that recombinant baculovirus Bac-Nte-Inx2 (reBac-Net-Inx2) and Bac-Nte-Inx3 (reBac-Nte-Inx3) closed the endogenous hemichannel on the Sf9 cell surface. Importantly, primary baculovirus infections significantly caused early apoptosis, and this apoptosis was reduced by hemichannel-closed Sf9 cells at 24-h post-infection (PI). Although N-terminal-elongated residue led to the increase in the phosphorylated sites in both Nte-Inx2 and Nte-Inx3 and an additional transmembrane domain in Nte-Inx3, both the proteins localized on the cell surface, suggesting Nte-Inxs proteins could mediate hemichannel closure. Further supporting evidence showed that hemichannel closure was dependent on N-Inxs expressed by baculovirus polyhedrin promoter, which began to express at 18-24 h PI. These results identify an unconventional function of N-terminal-elongated innexins that could act as a plug to manipulate hemichannel closure and provide a mechanism connecting the effect of hemichannel closure directly to apoptotic signaling transduction from intracellular to extracellular compartment. © 2016 Wiley Periodicals, Inc.

Connexin hemichannel inhibition reduces acetaminophen-induced liver injury in mice.

PubMed

Maes, Michaël; Crespo Yanguas, Sara; Willebrords, Joost; Weemhoff, James L; da Silva, Tereza Cristina; Decrock, Elke; Lebofsky, Margitta; Pereira, Isabel Veloso Alves; Leybaert, Luc; Farhood, Anwar; Jaeschke, Hartmut; Cogliati, Bruno; Vinken, Mathieu

2017-08-15

Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen. Prior to this, in vitro testing was performed to confirm the specificity and efficacy of TAT-Gap24 and TAT-Gap19 in blocking connexin32 and connexin43 hemichannels, respectively. Subsequently, mice were overdosed with acetaminophen followed by treatment with TAT-Gap24 or TAT-Gap19 or a combination of both after 1.5h. Sampling was performed 3, 6, 24 and 48h following acetaminophen administration. Evaluation of the effects of connexin hemichannel inhibition was based on a series of clinically relevant read-outs, measurement of inflammatory cytokines and oxidative stress. Subsequent treatment of acetaminophen-overdosed mice with TAT-Gap19 only marginally affected liver injury. In contrast, a significant reduction in serum alanine aminotransferase activity was found upon administration of TAT-Gap24 to intoxicated animals. Furthermore, co-treatment of acetaminophen-overdosed mice with both peptides revealed an additive effect as even lower serum alanine aminotransferase activity was observed. Blocking of connexin32 or connexin43 hemichannels individually was found to decrease serum quantities of pro-inflammatory cytokines, while no effects were observed on the occurrence of hepatic oxidative stress. This study shows for the first time a role for connexin hemichannels in acetaminophen-induced acute liver failure. Copyright © 2017 Elsevier B.V. All rights reserved.

Blockage of hemichannels alters gene expression in osteocytes in a high magneto-gravitational environment

PubMed Central

Xu, Huiyun; Ning, Dandan; Zhao, Dezhi; Chen, Yunhe; Zhao, Dongdong; Gu, Sumin; Jiang, Jean X.; Shang, Peng

2017-01-01

Osteocytes, the most abundant cells in bone, are highly responsive to external environmental changes. We tested how Cx43 hemichannels which mediate the exchange of small molecules between cells and extracellular environment impact genome wide gene expression under conditions of abnormal gravity and magnetic field. To this end, we subjected osteocytic MLO-Y4 cells to a high magneto-gravitational environment and used microarray to examine global gene expression and a specific blocking antibody was used to assess the role of Cx43 hemichannels. While 3 hr exposure to abnormal gravity and magnetic field had relatively minor effects on global gene expression, blocking hemichannels significantly impacted the expression of a number of genes which are involved in cell viability, apoptosis, mineral absorption, protein absorption and digestion, and focal adhesion. Also, blocking of hemichannels enriched genes in multiple signaling pathways which are enaged by TGF-beta, Jak-STAT and VEGF. These results show the role of connexin hemichannels in bone cells in high magneto-gravitational environments. PMID:27814646

TWO INNEXINS OF Spodoptera litura INFLUENCES HEMICHANNEL AND GAP JUNCTION FUNCTIONS IN CELLULAR IMMUNE RESPONSES.

PubMed

Pang, Zunyu; Li, Ming; Yu, Dongshuai; Yan, Zhang; Liu, Xinyi; Ji, Xinglai; Yang, Yang; Hu, Jiansheng; Luo, Kaijun

2015-09-01

Insect cellular immune responses include encapsulation, nodule formation, and phagocytosis. Hemichannels and gap junctions are involved in these cellular actions. Innexins (Inxs: analogous to the vertebrate connexins) form hemichannels and gap junctions, but the molecular mechanisms underlying their biology is still unclear. In this article, we reported a steady-state level of Inxs (SpliInxs) in hemocytes of Spodoptera litura, which formed nonfunctional hemichannels on the cell surface to maintain normal metabolism. We also reported that two innnexins (SpliInx2 and SpliInx3) were expressed significantly higher in hemocytes compared to other tissues, suggesting that they play important roles in hemocytes. Amino acid analysis found that two cysteine residues in two extracellular loops provided the capability for SpliInx2 and SpliInx3 hemichannels to dock into gap junctions. Western blotting demonstrated that both extracellular and intracellular loops of SpliInx3 and the extracellular loops of SpliInx2 might undergo posttranslational modification during the formation of a steady-state hemichannel. During hemichannel formation, SpliInx2 presented as one isoform, while SpliInx3 presented as three isoforms. These results provide fundamental knowledge for further study of how steady-state levels of SpliInxs are dynamically adjusted to perform cellular immune responses under immune challenge. © 2015 Wiley Periodicals, Inc.

Modulation of Brain Hemichannels and Gap Junction Channels by Pro-Inflammatory Agents and Their Possible Role in Neurodegeneration

PubMed Central

Sáez, Pablo J.; Shoji, Kenji F.; Schalper, Kurt A.; Palacios–Prado, Nicolás; Velarde, Victoria; Giaume, Christian; Bennett, Michael V.L.; Sáez, Juan C.

2009-01-01

Abstract In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process. Antiox. Redox Signal. 11, 369–399. PMID:18816186

Gap junction- and hemichannel-independent actions of connexins.

PubMed

Jiang, Jean X; Gu, Sumin

2005-06-10

Connexins have been known to be the protein building blocks of gap junctions and mediate cell-cell communication. In contrast to the conventional dogma, recent evidence suggests that in addition to forming gap junction channels, connexins possess gap junction-independent functions. One important gap junction-independent function for connexins is to serve as the major functional component for hemichannels, the un-apposed halves of gap junctions. Hemichannels, as independent functional units, play roles that are different from that of gap junctions in the cell. The other functions of connexins appear to be gap junction- and hemichannel-independent. Published studies implicate the latter functions of connexins in cell growth, differentiation, tumorigenicity, injury, and apoptosis, although the mechanistic aspects of these actions remain largely unknown. In this review, gap junction- and hemichannel-independent functions of connexins are summarized, and the molecular mechanisms underlying these connexin functions are speculated and discussed.

Involvement of connexin43 in the infrasonic noise-induced glutamate release by cultured astrocytes.

PubMed

Jiang, Shan; Wang, Yong-Qiang; Xu, Cheng-Feng; Li, Ya-Na; Guo, Rong; Li, Ling

2014-05-01

Infrasonic noise/infrasound is a type of environmental noise that threatens public health as a nonspecific biological stressor. Glutamate-related excitotoxicity is thought to be responsible for infrasound-induced impairment of learning and memory. In addition to neurons, astrocytes are also capable of releasing glutamate. In the present study, to identify the effect of infrasound on astroglial glutamate release, cultured astrocytes were exposed to infrasound at 16 Hz, 130 dB for different times. We found that infrasound exposure caused a significant increase in glutamate levels in the extracellular fluid. Moreover, blocking the connexin43 (Cx43) hemichannel or gap junction, decreasing the probability of Cx43 being open or inhibiting of Cx43 expression blocked this increase. The results suggest that glutamate release by Cx43 hemichannels/gap junctions is involved in the response of cultured astrocytes to infrasound.

Hemichannels in neurodegenerative diseases: is there a link to pathology?

PubMed Central

Bosch, Megan; Kielian, Tammy

2014-01-01

Although originally considered a structural component of gap junctions, connexin hemichannels (HCs) are now recognized as functional entities capable of influencing metabolic gradients within the CNS, allowing direct communication between the intra- and extracellular milieus. Besides connexins, HCs can also be formed by pannexins, which are not capable of gap junction assembly. Both positive and negative effects have been attributed to HC activity in the context of neurodegenerative diseases. For example, HCs can exert neuroprotective effects by promoting the uptake of neurotoxic molecules, whereas chronic HC opening can disrupt molecular gradients leading to cellular dysfunction and death. The latter scenario has been suggested for multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and more recently, lysosomal storage disorders, which are the focus of this perspective. Currently available evidence suggests a complex role for HCs in neurodegenerative disorders, which sets the stage for future studies to determine whether targeting HC action may improve disease outcomes. PMID:25191227

Inhibition of Connexin 43 Hemichannel-Mediated ATP Release Attenuates Early Inflammation During the Foreign Body Response

PubMed Central

Calder, Bennett W.; Rhett, Joshua Matthew; Bainbridge, Heather; Fann, Stephen A.; Gourdie, Robert G.

2015-01-01

Background: In the last 50 years, the use of medical implants has increased dramatically. Failure of implanted devices and biomaterials is a significant source of morbidity and increasing healthcare expenditures. An important cause of implant failure is the host inflammatory response. Recent evidence implicates extracellular ATP as an important inflammatory signaling molecule. A major pathway for release of cytoplasmic ATP into the extracellular space is through connexin hemichannels, which are the unpaired constituents of gap junction intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43) isoform has been shown to reduce inflammation and improve healing. We have developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding domain of Cx43. The following report investigates the role of the Cx43 microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and how this impacts early inflammatory events of the foreign body reaction. Methods: In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular endothelial cells subjected to hypocalcemic and normocalcemic conditions was measured after application of JM2 and the known hemichannel blocker, flufenamic acid. A submuscular silicone implant model was used to investigate in vivo ATP signaling during the early foreign body response. Implants were coated with control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known hemichannel blockers and harvested at 24 h for analysis. Results: JM2 significantly inhibited connexin hemichannel-mediated ATP release from cultured endothelial cells. Importantly, the early inflammatory response to submuscular silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was reversed by the addition of exogenous ATP to the pluronic vehicle. Conclusions: These data indicate that ATP released through Cx43 hemichannels into the vasculature is an important signal driving the early inflammatory response to implanted devices. A vital aspect of this work is that it demonstrates that targeted molecular therapeutics, such as JM2, provide the capacity to regulate inflammation in a clinically relevant system. PMID:25760687

Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early inflammation during the foreign body response.

PubMed

Calder, Bennett W; Matthew Rhett, Joshua; Bainbridge, Heather; Fann, Stephen A; Gourdie, Robert G; Yost, Michael J

2015-06-01

In the last 50 years, the use of medical implants has increased dramatically. Failure of implanted devices and biomaterials is a significant source of morbidity and increasing healthcare expenditures. An important cause of implant failure is the host inflammatory response. Recent evidence implicates extracellular ATP as an important inflammatory signaling molecule. A major pathway for release of cytoplasmic ATP into the extracellular space is through connexin hemichannels, which are the unpaired constituents of gap junction intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43) isoform has been shown to reduce inflammation and improve healing. We have developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding domain of Cx43. The following report investigates the role of the Cx43 microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and how this impacts early inflammatory events of the foreign body reaction. In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular endothelial cells subjected to hypocalcemic and normocalcemic conditions was measured after application of JM2 and the known hemichannel blocker, flufenamic acid. A submuscular silicone implant model was used to investigate in vivo ATP signaling during the early foreign body response. Implants were coated with control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known hemichannel blockers and harvested at 24 h for analysis. JM2 significantly inhibited connexin hemichannel-mediated ATP release from cultured endothelial cells. Importantly, the early inflammatory response to submuscular silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was reversed by the addition of exogenous ATP to the pluronic vehicle. These data indicate that ATP released through Cx43 hemichannels into the vasculature is an important signal driving the early inflammatory response to implanted devices. A vital aspect of this work is that it demonstrates that targeted molecular therapeutics, such as JM2, provide the capacity to regulate inflammation in a clinically relevant system.

How Shigella Utilizes Ca(2+) Jagged Edge Signals during Invasion of Epithelial Cells.

PubMed

Bonnet, Mariette; Tran Van Nhieu, Guy

2016-01-01

Shigella, the causative agent of bacillary dysentery invades intestinal epithelial cells using a type III secretion system (T3SS). Through the injection of type III effectors, Shigella manipulates the actin cytoskeleton to induce its internalization in epithelial cells. At early invasion stages, Shigella induces atypical Ca(2+) responses confined at entry sites allowing local cytoskeletal remodeling for bacteria engulfment. Global Ca(2+) increase in the cell triggers the opening of connexin hemichannels at the plasma membrane that releases ATP in the extracellular milieu, favoring Shigella invasion and spreading through purinergic receptor signaling. During intracellular replication, Shigella regulates inflammatory and death pathways to disseminate within the epithelium. At later stages of infection, Shigella downregulates hemichannel opening and the release of extracellular ATP to dampen inflammatory signals. To avoid premature cell death, Shigella activates cell survival by upregulating the PI3K/Akt pathway and downregulating the levels of p53. Furthermore, Shigella interferes with pro-apoptotic caspases, and orients infected cells toward a slow necrotic cell death linked to mitochondrial Ca(2+) overload. In this review, we will focus on the role of Ca(2+) responses and their regulation by Shigella during the different stages of bacterial infection.

How Shigella Utilizes Ca2+ Jagged Edge Signals during Invasion of Epithelial Cells

PubMed Central

Bonnet, Mariette; Tran Van Nhieu, Guy

2016-01-01

Shigella, the causative agent of bacillary dysentery invades intestinal epithelial cells using a type III secretion system (T3SS). Through the injection of type III effectors, Shigella manipulates the actin cytoskeleton to induce its internalization in epithelial cells. At early invasion stages, Shigella induces atypical Ca2+ responses confined at entry sites allowing local cytoskeletal remodeling for bacteria engulfment. Global Ca2+ increase in the cell triggers the opening of connexin hemichannels at the plasma membrane that releases ATP in the extracellular milieu, favoring Shigella invasion and spreading through purinergic receptor signaling. During intracellular replication, Shigella regulates inflammatory and death pathways to disseminate within the epithelium. At later stages of infection, Shigella downregulates hemichannel opening and the release of extracellular ATP to dampen inflammatory signals. To avoid premature cell death, Shigella activates cell survival by upregulating the PI3K/Akt pathway and downregulating the levels of p53. Furthermore, Shigella interferes with pro-apoptotic caspases, and orients infected cells toward a slow necrotic cell death linked to mitochondrial Ca2+ overload. In this review, we will focus on the role of Ca2+ responses and their regulation by Shigella during the different stages of bacterial infection. PMID:26904514

Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood–brain barrier permeability

PubMed Central

De Bock, Marijke; Culot, Maxime; Wang, Nan; Bol, Mélissa; Decrock, Elke; De Vuyst, Elke; da Costa, Anaelle; Dauwe, Ine; Vinken, Mathieu; Simon, Alexander M; Rogiers, Vera; De Ley, Gaspard; Evans, William Howard; Bultynck, Geert; Dupont, Geneviève; Cecchelli, Romeo; Leybaert, Luc

2011-01-01

The cytoplasmic Ca2+ concentration ([Ca2+]i) is an important factor determining the functional state of blood–brain barrier (BBB) endothelial cells but little is known on the effect of dynamic [Ca2+]i changes on BBB function. We applied different agonists that trigger [Ca2+]i oscillations and determined the involvement of connexin channels and subsequent effects on endothelial permeability in immortalized and primary brain endothelial cells. The inflammatory peptide bradykinin (BK) triggered [Ca2+]i oscillations and increased endothelial permeability. The latter was prevented by buffering [Ca2+]i with BAPTA, indicating that [Ca2+]i oscillations are crucial in the permeability changes. Bradykinin-triggered [Ca2+]i oscillations were inhibited by interfering with connexin channels, making use of carbenoxolone, Gap27, a peptide blocker of connexin channels, and Cx37/43 knockdown. Gap27 inhibition of the oscillations was rapid (within minutes) and work with connexin hemichannel-permeable dyes indicated hemichannel opening and purinergic signaling in response to stimulation with BK. Moreover, Gap27 inhibited the BK-triggered endothelial permeability increase in in vitro and in vivo experiments. By contrast, [Ca2+]i oscillations provoked by exposure to adenosine 5′ triphosphate (ATP) were not affected by carbenoxolone or Gap27 and ATP did not disturb endothelial permeability. We conclude that interfering with endothelial connexin hemichannels is a novel approach to limiting BBB-permeability alterations. PMID:21654699

Asparagine 175 of connexin32 is a critical residue for docking and forming functional heterotypic gap junction channels with connexin26.

PubMed

Nakagawa, So; Gong, Xiang-Qun; Maeda, Shoji; Dong, Yuhua; Misumi, Yuko; Tsukihara, Tomitake; Bai, Donglin

2011-06-03

The gap junction channel is formed by proper docking of two hemichannels. Depending on the connexin(s) in the hemichannels, homotypic and heterotypic gap junction channels can be formed. Previous studies suggest that the extracellular loop 2 (E2) is an important molecular domain for heterotypic compatibility. Based on the crystal structure of the Cx26 gap junction channel and homology models of heterotypic channels, we analyzed docking selectivity for several hemichannel pairs and found that the hydrogen bonds between E2 domains are conserved in a group of heterotypically compatible hemichannels, including Cx26 and Cx32 hemichannels. According to our model analysis, Cx32N175Y mutant destroys three hydrogen bonds in the E2-E2 interactions due to steric hindrance at the heterotypic docking interface, which makes it unlikely to dock with the Cx26 hemichannel properly. Our experimental data showed that Cx26-red fluorescent protein (RFP) and Cx32-GFP were able to traffic to cell-cell interfaces forming gap junction plaques and functional channels in transfected HeLa/N2A cells. However, Cx32N175Y-GFP exhibited mostly intracellular distribution and was occasionally observed in cell-cell junctions. Double patch clamp analysis demonstrated that Cx32N175Y did not form functional homotypic channels, and dye uptake assay indicated that Cx32N175Y could form hemichannels on the cell surface similar to wild-type Cx32. When Cx32N175Y-GFP- and Cx26-RFP-transfected cells were co-cultured, no colocalization was found at the cell-cell junctions between Cx32N175Y-GFP- and Cx26-RFP-expressing cells; also, no functional Cx32N175Y-GFP/Cx26-RFP heterotypic channels were identified. Both our modeling and experimental data suggest that Asn(175) of Cx32 is a critical residue for heterotypic docking and functional gap junction channel formation between the Cx32 and Cx26 hemichannels.

Molecular dynamics simulation of the thermosensitivity of the human connexin 26 hemichannel

NASA Astrophysics Data System (ADS)

Alizadeh, Hadi; Davoodi, Jamal; Zeilinger, Carsten; Rafii-Tabar, Hashem

2018-01-01

Connexin hemichannels mediate cytoplasm and extracellular milieu communication by exchanging a variety of cytoplasmic molecules and ions. These hemichannels can be regulated by external stimuli such as mechanical stress, applied voltage, pH and temperature changes. Although there are many studies on structures and functions of connexin 26 in contexts of pH, ion concentration and voltage, employing computational methods, no such study has been performed so far involving temperature changes. In this study, using molecular dynamics simulation, we investigate thermosensitivity of the human Connexin 26 hemichannel. Our results show that the channel approaches a structurally closed state at lower temperature compared to higher temperature. This is in fair agreement with experimental results that indicate channel closure at lower temperature. Furthermore, our MD simulation results show that some regions of connexin 26 hemichannel are more sensitive to temperature compared to other regions. Whereas the intercellular half of the channel does not show any considerable response to temperature during the simulation time accessible in this study, the cytoplasmic half approaches a closed structural state at lower temperature compared to the higher temperature. Specifically, our results suggest that the cytoplasmic loop, the cytoplasmic half of the second transmembrane helix, and the N-terminus helix play a dominant role in temperature gating.

Control of the neurovascular coupling by nitric oxide-dependent regulation of astrocytic Ca2+ signaling

PubMed Central

Muñoz, Manuel F.; Puebla, Mariela; Figueroa, Xavier F.

2015-01-01

Neuronal activity must be tightly coordinated with blood flow to keep proper brain function, which is achieved by a mechanism known as neurovascular coupling. Then, an increase in synaptic activity leads to a dilation of local parenchymal arterioles that matches the enhanced metabolic demand. Neurovascular coupling is orchestrated by astrocytes. These glial cells are located between neurons and the microvasculature, with the astrocytic endfeet ensheathing the vessels, which allows fine intercellular communication. The neurotransmitters released during neuronal activity reach astrocytic receptors and trigger a Ca2+ signaling that propagates to the endfeet, activating the release of vasoactive factors and arteriolar dilation. The astrocyte Ca2+ signaling is coordinated by gap junction channels and hemichannels formed by connexins (Cx43 and Cx30) and channels formed by pannexins (Panx-1). The neuronal activity-initiated Ca2+ waves are propagated among neighboring astrocytes directly via gap junctions or through ATP release via connexin hemichannels or pannexin channels. In addition, Ca2+ entry via connexin hemichannels or pannexin channels may participate in the regulation of the astrocyte signaling-mediated neurovascular coupling. Interestingly, nitric oxide (NO) can activate connexin hemichannel by S-nitrosylation and the Ca2+-dependent NO-synthesizing enzymes endothelial NO synthase (eNOS) and neuronal NOS (nNOS) are expressed in astrocytes. Therefore, the astrocytic Ca2+ signaling triggered in neurovascular coupling may activate NO production, which, in turn, may lead to Ca2+ influx through hemichannel activation. Furthermore, NO release from the hemichannels located at astrocytic endfeet may contribute to the vasodilation of parenchymal arterioles. In this review, we discuss the mechanisms involved in the regulation of the astrocytic Ca2+ signaling that mediates neurovascular coupling, with a special emphasis in the possible participation of NO in this process. PMID:25805969

HIV increased the release of dickkopf-1 (DKK1) protein from human astrocytes by a Cx43 hemichannel-dependent mechanism

PubMed Central

Orellana, Juan Andres; Sáez, Juan Carlos; Bennett, Michael Vander Lann; Berman, Joan Weinberger; Morgello, Susan; Eugenin, Eliseo Alberto

2015-01-01

Human immunodeficiency virus-1 (HIV) is a public health issue and a major complication of the disease is NeuroAIDS. In vivo, microglia/macrophages are the main cells infected. However, a low but significant number of HIV infected astrocytes also has been detected, but their role in the pathogenesis of NeuroAIDS is not well understood. Our previous data indicates that gap junction channels amplify toxicity from few HIV infected into uninfected astrocytes. Now, we demonstrated that HIV infection of astrocytes results in opening of connexin43 hemichannels (Cx43 HCs). HIV induced opening of Cx43 HCs resulted in dysregulated secretion of dickkopf-1 protein (DKK1, a soluble wnt pathway inhibitor). Treatment of mixed cultures of neurons and astrocytes with DKK1, in the absence of HIV infection, resulted in collapse of neuronal processes. HIV infection of mixed cultures of human neurons and astrocytes also resulted in collapse of neuronal processes by a DKK1 dependent mechanism. In addition, dysregulated DKK1 expression in astrocytes was observed in human brain tissue sections of individuals with HIV encephalitis as compared to tissue sections from uninfected individuals. Thus, we demonstrated that HIV infection of astrocytes induces dysregulation of DKK1 by a HC-dependent mechanism that contributes to the brain pathogenesis observed in HIV infected individuals. PMID:24134157

Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders

PubMed Central

Xu, Liang; Carrer, Andrea; Zonta, Francesco; Qu, Zhihu; Ma, Peixiang; Li, Sheng; Ceriani, Federico; Buratto, Damiano; Crispino, Giulia; Zorzi, Veronica; Ziraldo, Gaia; Bruno, Francesca; Nardin, Chiara; Peres, Chiara; Mazzarda, Flavia; Salvatore, Anna M.; Raspa, Marcello; Scavizzi, Ferdinando; Chu, Youjun; Xie, Sichun; Yang, Xuemei; Liao, Jun; Liu, Xiao; Wang, Wei; Wang, Shanshan; Yang, Guang; Lerner, Richard A.; Mammano, Fabio

2017-01-01

Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26), a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity. Methods: By screening a combinatorial library of human single-chain fragment variable (scFv) antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells. Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID) syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action. Conclusions: Although further studies will be necessary to validate the effect of the antibody in vivo, the methodology described here can be extended to select antibodies against hemichannels composed by other connexin isoforms and, consequently, to target other pathologies associated with hyperactive hemichannels. Our study highlights the potential of this approach and identifies connexins as therapeutic targets addressable by screening phage display libraries expressing human randomized antibodies. PMID:29018324

Characterization of a Novel Water Pocket Inside the Human Cx26 Hemichannel Structure

PubMed Central

Araya-Secchi, Raul; Perez-Acle, Tomas; Kang, Seung-gu; Huynh, Tien; Bernardin, Alejandro; Escalona, Yerko; Garate, Jose-Antonio; Martínez, Agustin D.; García, Isaac E.; Sáez, Juan C.; Zhou, Ruhong

2014-01-01

Connexins (Cxs) are a family of vertebrate proteins constituents of gap junction channels (GJCs) that connect the cytoplasm of adjacent cells by the end-to-end docking of two Cx hemichannels. The intercellular transfer through GJCs occurs by passive diffusion allowing the exchange of water, ions, and small molecules. Despite the broad interest to understand, at the molecular level, the functional state of Cx-based channels, there are still many unanswered questions regarding structure-function relationships, perm-selectivity, and gating mechanisms. In particular, the ordering, structure, and dynamics of water inside Cx GJCs and hemichannels remains largely unexplored. In this work, we describe the identification and characterization of a believed novel water pocket—termed the IC pocket—located in-between the four transmembrane helices of each human Cx26 (hCx26) monomer at the intracellular (IC) side. Using molecular dynamics (MD) simulations to characterize hCx26 internal water structure and dynamics, six IC pockets were identified per hemichannel. A detailed characterization of the dynamics and ordering of water including conformational variability of residues forming the IC pockets, together with multiple sequence alignments, allowed us to propose a functional role for this cavity. An in vitro assessment of tracer uptake suggests that the IC pocket residue Arg-143 plays an essential role on the modulation of the hCx26 hemichannel permeability. PMID:25099799

Keratitis-Ichthyosis-Deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43

PubMed Central

García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.

2015-01-01

Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422

Role of connexin 32 hemichannels in the release of ATP from peripheral nerves.

PubMed

Nualart-Marti, Anna; del Molino, Ezequiel Mas; Grandes, Xènia; Bahima, Laia; Martin-Satué, Mireia; Puchal, Rafel; Fasciani, Ilaria; González-Nieto, Daniel; Ziganshin, Bulat; Llobet, Artur; Barrio, Luis C; Solsona, Carles

2013-12-01

Extracellular purines elicit strong signals in the nervous system. Adenosine-5'-triphosphate (ATP) does not spontaneously cross the plasma membrane, and nervous cells secrete ATP by exocytosis or through plasma membrane proteins such as connexin hemichannels. Using a combination of imaging, luminescence and electrophysiological techniques, we explored the possibility that Connexin 32 (Cx32), expressed in Schwann cells (SCs) myelinating the peripheral nervous system could be an important source of ATP in peripheral nerves. We triggered the release of ATP in vivo from mice sciatic nerves by electrical stimulation and from cultured SCs by high extracellular potassium concentration-evoked depolarization. No ATP was detected in the extracellular media after treatment of the sciatic nerve with Octanol or Carbenoxolone, and ATP release was significantly inhibited after silencing Cx32 from SCs cultures. We investigated the permeability of Cx32 to ATP by expressing Cx32 hemichannels in Xenopus laevis oocytes. We found that ATP release is coupled to the inward tail current generated after the activation of Cx32 hemichannels by depolarization pulses, and it is sensitive to low extracellular calcium concentrations. Moreover, we found altered ATP release in mutated Cx32 hemichannels related to the X-linked form of Charcot-Marie-Tooth disease, suggesting that purinergic-mediated signaling in peripheral nerves could underlie the physiopathology of this neuropathy. Copyright © 2013 Wiley Periodicals, Inc.

Oxaliplatin-induced neurotoxicity is mediated through gap junction channels and hemichannels and can be prevented by octanol.

PubMed

Kagiava, Alexia; Theophilidis, George; Sargiannidou, Irene; Kyriacou, Kyriacos; Kleopa, Kleopas A

2015-10-01

Oxaliplatin-induced neurotoxicity (OIN) is a common complication of chemotherapy without effective treatment. In order to clarify the mechanisms of both acute and chronic OIN, we used an ex-vivo mouse sciatic nerve model. Exposure to 25 μM oxaliplatin caused a marked prolongation in the duration of the nerve evoked compound action potential (CAP) by nearly 1200% within 300 min while amplitude remained constant for over 20 h. This oxaliplatin effect was almost completely reversed by the gap junction (GJ) inhibitor octanol in a concentration-dependent manner. Further GJ blockers showed similar effects although with a narrower therapeutic window. To clarify the target molecule we studied sciatic nerves from connexin32 (Cx32) and Cx29 knockout (KO) mice. The oxaliplatin effect and neuroprotection by octanol partially persisted in Cx29 better than in Cx32 KO nerves, suggesting that oxaliplatin affects both, but Cx32 GJ channels more than Cx29 hemichannels. Oxaliplatin also accelerated neurobiotin uptake in HeLa cells expressing the human ortholog of Cx29, Cx31.3, as well as dye transfer between cells expressing the human Cx32, and this effect was blocked by octanol. Oxaliplatin caused no morphological changes initially (up to 3 h of exposure), but prolonged nerve exposure caused juxtaparonodal axonal edema, which was prevented by octanol. Our study indicates that oxaliplatin causes forced opening of Cx32 channels and Cx29 hemichannels in peripheral myelinated fibers leading to disruption of axonal K(+) homeostasis. The GJ blocker octanol prevents OIN at very low concentrations and should be further studied as a neuroprotectant. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

PubMed

Le, Hoa T; Sin, Wun Chey; Lozinsky, Shannon; Bechberger, John; Vega, José Luis; Guo, Xu Qiu; Sáez, Juan C; Naus, Christian C

2014-01-17

Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

Analysis of trafficking, stability and function of human connexin 26 gap junction channels with deafness-causing mutations in the fourth transmembrane helix.

PubMed

Ambrosi, Cinzia; Walker, Amy E; Depriest, Adam D; Cone, Angela C; Lu, Connie; Badger, John; Skerrett, I Martha; Sosinsky, Gina E

2013-01-01

Human Connexin26 gene mutations cause hearing loss. These hereditary mutations are the leading cause of childhood deafness worldwide. Mutations in gap junction proteins (connexins) can impair intercellular communication by eliminating protein synthesis, mis-trafficking, or inducing channels that fail to dock or have aberrant function. We previously identified a new class of mutants that form non-functional gap junction channels and hemichannels (connexons) by disrupting packing and inter-helix interactions. Here we analyzed fourteen point mutations in the fourth transmembrane helix of connexin26 (Cx26) that cause non-syndromic hearing loss. Eight mutations caused mis-trafficking (K188R, F191L, V198M, S199F, G200R, I203K, L205P, T208P). Of the remaining six that formed gap junctions in mammalian cells, M195T and A197S formed stable hemichannels after isolation with a baculovirus/Sf9 protein purification system, while C202F, I203T, L205V and N206S formed hemichannels with varying degrees of instability. The function of all six gap junction-forming mutants was further assessed through measurement of dye coupling in mammalian cells and junctional conductance in paired Xenopus oocytes. Dye coupling between cell pairs was reduced by varying degrees for all six mutants. In homotypic oocyte pairings, only A197S induced measurable conductance. In heterotypic pairings with wild-type Cx26, five of the six mutants formed functional gap junction channels, albeit with reduced efficiency. None of the mutants displayed significant alterations in sensitivity to transjunctional voltage or induced conductive hemichannels in single oocytes. Intra-hemichannel interactions between mutant and wild-type proteins were assessed in rescue experiments using baculovirus expression in Sf9 insect cells. Of the four unstable mutations (C202F, I203T, L205V, N206S) only C202F and N206S formed stable hemichannels when co-expressed with wild-type Cx26. Stable M195T hemichannels displayed an increased tendency to aggregate. Thus, mutations in TM4 cause a range of phenotypes of dysfunctional gap junction channels that are discussed within the context of the X-ray crystallographic structure.

Gap Junctions and Connexin Hemichannels Underpin Haemostasis and Thrombosis

PubMed Central

Vaiyapuri, Sakthivel; Jones, Chris I.; Sasikumar, Parvathy; Moraes, Leonardo A.; Munger, Stephanie J.; Wright, Joy R.; Ali, Marfoua S.; Sage, Tanya; Kaiser, William J.; Tucker, Katherine L.; Stain, Christopher J.; Bye, Alexander P.; Jones, Sarah; Oviedo-Orta, Ernesto; Simon, Alexander M.; Mahaut-Smith, Martyn P.; Gibbins, Jonathan M.

2012-01-01

Background Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have now examined the role of connexins in platelets, blood cells that circulate in isolation, but upon tissue injury adhere to each other and the vessel wall to prevent blood loss and facilitate wound repair. Methods and Results We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. Inhibition of connexin function modulated a range of platelet functional responses prior to platelet-platelet contact, and reduced laser induced thrombosis in vivo in mice. Deletion of the Cx37 gene (Gja4) in transgenic mice reduced platelet aggregation, fibrinogen binding, granule secretion and clot retraction indicating an important role for Cx37 hemichannels and gap junctions in platelet thrombus function. Conclusions Together, these data demonstrate that platelet gap junctions and hemichannels underpin the control of haemostasis and thrombosis and represent potential therapeutic targets. PMID:22528526

Redox-mediated regulation of connexin proteins; focus on nitric oxide.

PubMed

García, Isaac E; Sánchez, Helmuth A; Martínez, Agustín D; Retamal, Mauricio A

2018-01-01

Connexins are membrane proteins that form hemichannels and gap junction channels at the plasma membrane. Through these channels connexins participate in autocrine and paracrine intercellular communication. Connexin-based channels are tightly regulated by membrane potential, phosphorylation, pH, redox potential, and divalent cations, among others, and the imbalance of this regulation have been linked to many acquired and genetic diseases. Concerning the redox potential regulation, the nitric oxide (NO) has been described as a modulator of the hemichannels and gap junction channels properties. However, how NO regulates these channels is not well understood. In this mini-review, we summarize the current knowledge about the effects of redox potential focused in NO on the trafficking, formation and functional properties of hemichannels and gap junction channels. Copyright © 2017 Elsevier B.V. All rights reserved.

Physiological Role of Gap-Junctional Hemichannels

PubMed Central

Quist, Arjan Pieter; Rhee, Seung Keun; Lin, Hai; Lal, Ratneshwar

2000-01-01

Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to ≤1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and β-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation. PMID:10704454

The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity

PubMed Central

Mhaske, Pallavi V.; Levit, Noah A.; Li, Leping; Wang, Hong-Zhan; Lee, Jack R.; Shuja, Zunaira; Brink, Peter R.

2013-01-01

Mutations in the human gene encoding connexin 26 (Cx26 or GJB2) cause either nonsyndromic deafness or syndromic deafness associated with skin diseases. That distinct clinical disorders can be caused by different mutations within the same gene suggests that different channel activities influence the ear and skin. Here we use three different expression systems to examine the functional characteristics of two Cx26 mutations causing either mild (Cx26-D50A) or lethal (Cx26-A88V) keratitis-ichthyosis-deafness (KID) syndrome. In either cRNA-injected Xenopus oocytes, transfected HeLa cells, or transfected primary human keratinocytes, we show that both Cx26-D50A and Cx26-A88V form active hemichannels that significantly increase membrane current flow compared with wild-type Cx26. This increased membrane current accelerated cell death in low extracellular calcium solutions and was not due to increased mutant protein expression. Elevated mutant hemichannel currents could be blocked by increased extracellular calcium concentration. These results show that these two mutations exhibit a shared gain of functional activity and support the hypothesis that increased hemichannel activity is a common feature of human Cx26 mutations responsible for KID syndrome. PMID:23447037

Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep.

PubMed

Davidson, Joanne O; Drury, Paul P; Green, Colin R; Nicholson, Louise F; Bennet, Laura; Gunn, Alistair J

2014-01-01

Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103-104 d gestational age). Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6) or vehicle infusion for controls (occlusion-vehicle group, n = 7). Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p<0.05), with reduced neuronal loss in the caudate and putamen (p<0.05), but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p<0.05) and immature/mature oligodendrocytes compared to occlusion-vehicle (p<0.05), with a significant increase in proliferation (p<0.05). Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia.

Connexin Hemichannel Blockade Is Neuroprotective after Asphyxia in Preterm Fetal Sheep

PubMed Central

Davidson, Joanne O.; Drury, Paul P.; Green, Colin R.; Nicholson, Louise F.; Bennet, Laura; Gunn, Alistair J.

2014-01-01

Asphyxia around the time of preterm birth is associated with neurodevelopmental disability. In this study, we tested the hypothesis that blockade of connexin hemichannels would improve recovery of brain activity and reduce cell loss after asphyxia in preterm fetal sheep. Asphyxia was induced by 25 min of complete umbilical cord occlusion in preterm fetal sheep (103–104 d gestational age). Connexin hemichannels were blocked by intracerebroventricular infusion of mimetic peptide starting 90 min after asphyxia at a concentration of 50 µM/h for one hour followed by 50 µM/24 hour for 24 hours (occlusion-peptide group, n = 6) or vehicle infusion for controls (occlusion-vehicle group, n = 7). Peptide infusion was associated with earlier recovery of electroencephalographic power after asphyxia compared to occlusion-vehicle (p<0.05), with reduced neuronal loss in the caudate and putamen (p<0.05), but not in the hippocampus. In the intragyral and periventricular white matter, peptide administration was associated with an increase in total oligodendrocyte numbers (p<0.05) and immature/mature oligodendrocytes compared to occlusion-vehicle (p<0.05), with a significant increase in proliferation (p<0.05). Connexin hemichannel blockade was neuroprotective and reduced oligodendrocyte death and improved recovery of oligodendrocyte maturation in preterm fetuses after asphyxia. PMID:24865217

Hemichannel composition and electrical synaptic transmission: molecular diversity and its implications for electrical rectification

PubMed Central

Palacios-Prado, Nicolás; Huetteroth, Wolf; Pereda, Alberto E.

2014-01-01

Unapposed hemichannels (HCs) formed by hexamers of gap junction proteins are now known to be involved in various cellular processes under both physiological and pathological conditions. On the other hand, less is known regarding how differences in the molecular composition of HCs impact electrical synaptic transmission between neurons when they form intercellular heterotypic gap junctions (GJs). Here we review data indicating that molecular differences between apposed HCs at electrical synapses are generally associated with rectification of electrical transmission. Furthermore, this association has been observed at both innexin and connexin (Cx) based electrical synapses. We discuss the possible molecular mechanisms underlying electrical rectification, as well as the potential contribution of intracellular soluble factors to this phenomenon. We conclude that asymmetries in molecular composition and sensitivity to cellular factors of each contributing hemichannel can profoundly influence the transmission of electrical signals, endowing electrical synapses with more complex functional properties. PMID:25360082

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Han; Zheng, Gang; Liu, Yang

As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CPmore » cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk activation causes reduction of Cx43.« less

MRP transporters as membrane machinery in the bradykinin-inducible export of ATP.

PubMed

Zhao, Yumei; Migita, Keisuke; Sun, Jing; Katsuragi, Takeshi

2010-04-01

Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-) channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.

Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells In the Absence of a Leader Sequence Through a Pannexin-1 Interactome

PubMed Central

Atanasova, Kalina; Lee, Jungnam; Roberts, JoAnn; Lee, Kyulim; Ojcius, David M; Yilmaz, Özlem

2016-01-01

Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co-cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation induced NDK recruitment to the cell periphery. Depletion of PNX1 by siRNA or inhibition by probenecid resulted in significant blocking of extracellular NDK activity and secretion using ATPase and ELISA assays. Co-immunoprecipitation-coupled Mass-spectrometry method revealed association of P. gingivalis-NDK to the myosin-9 motor molecule. Interestingly, inhibition of myosin-9, actin, and lipid-rafts, shown to be involved in PNX1-hemichannel function, resulted in marked intracellular accumulation of NDK and decreased NDK secretion from infected GECs. These results elucidate for the first time PNX1-hemichannels as potentially main extracellular translocation pathway for NDKs from an intracellular pathogen, suggesting that PNX1-hemichannels may represent a therapeutic target for chronic opportunistic infections. PMID:27883084

Joint diseases: from connexins to gap junctions.

PubMed

Donahue, Henry J; Qu, Roy W; Genetos, Damian C

2017-12-19

Connexons form the basis of hemichannels and gap junctions. They are composed of six tetraspan proteins called connexins. Connexons can function as individual hemichannels, releasing cytosolic factors (such as ATP) into the pericellular environment. Alternatively, two hemichannel connexons from neighbouring cells can come together to form gap junctions, membrane-spanning channels that facilitate cell-cell communication by enabling signalling molecules of approximately 1 kDa to pass from one cell to an adjacent cell. Connexins are expressed in joint tissues including bone, cartilage, skeletal muscle and the synovium. Indicative of their importance as gap junction components, connexins are also known as gap junction proteins, but individual connexin proteins are gaining recognition for their channel-independent roles, which include scaffolding and signalling functions. Considerable evidence indicates that connexons contribute to the function of bone and muscle, but less is known about the function of connexons in other joint tissues. However, the implication that connexins and gap junctional channels might be involved in joint disease, including age-related bone loss, osteoarthritis and rheumatoid arthritis, emphasizes the need for further research into these areas and highlights the therapeutic potential of connexins.

A Mutant Connexin50 with Enhanced Hemichannel Function Leads to Cell Death

PubMed Central

Minogue, Peter J.; Tong, Jun-Jie; Arora, Anita; Russell-Eggitt, Isabelle; Hunt, David M.; Moore, Anthony T.; Ebihara, Lisa; Beyer, Eric C.; Berthoud, Viviana M.

2009-01-01

PURPOSE To determine the consequences of expression of a novel connexin50 (CX50) mutant identified in a child with congenital total cataracts. METHODS The GJA8 gene was directly sequenced. Formation of functional channels was assessed by two-microelectrode voltage-clamp. Connexin protein levels and distribution were assessed by immunoblotting and immunofluorescence. The proportion of apoptotic cells was determined by flow cytometry. RESULTS Direct sequencing of the GJA8 gene identified a 137 G>T transition that resulted in the replacement of glycine by valine at position 46 of the coding region of CX50 (CX50G46V). Both CX50 and CX50G46V induced gap junctional currents in pairs of Xenopus oocytes. In single Xenopus oocytes, CX50G46V induced connexin hemichannel currents that were activated by removal of external calcium; their magnitudes were much higher than those in oocytes injected with similar amounts of CX50 cRNA. When expressed in HeLa cells under the control of an inducible promoter, both CX50 and CX50G46V formed gap junctional plaques. Induction of CX50G46V expression led to a decrease in cell number and an increase in the proportion of apoptotic cells. CX50G46V-induced cell death was prevented by high concentrations of extracellular calcium ions. CONCLUSIONS Unlike previously characterized CX50 mutants that exhibit impaired trafficking and/or lack of function, CX50G46V traffics properly to the plasma membrane and forms functional hemichannels and gap junction channels; however, it causes cell death even when expressed at minute levels. The biochemical results indirectly suggest a potential novel mechanism by which connexin mutants could lead to cataracts: cytotoxicity due to enhanced hemichannel function. PMID:19684000

Hydrostatic pressure activates ATP-sensitive K+ channels in lung epithelium by ATP release through pannexin and connexin hemichannels.

PubMed

Richter, Katrin; Kiefer, Kevin P; Grzesik, Benno A; Clauss, Wolfgang G; Fronius, Martin

2014-01-01

Lungs of air-breathing vertebrates are constantly exposed to mechanical forces and therefore are suitable for investigation of mechanotransduction processes in nonexcitable cells and tissues. Freshly dissected Xenopus laevis lungs were used for transepithelial short-circuit current (ISC) recordings and were exposed to increased hydrostatic pressure (HP; 5 cm fluid column, modified Ussing chamber). I(SC) values obtained under HP (I(5cm)) were normalized to values before HP (I(0cm)) application (I(5cm)/I(0cm)). Under control conditions, HP decreased I(SC) (I(5cm)/I(0cm)=0.84; n=68; P<0.0001). This effect was reversible and repeatable ≥30 times. Preincubation with ATP-sensitive K(+) channel (K(ATP)) inhibitors (HMR1098 and glibenclamide) prevented the decrease in I(SC) (I(5cm)/I(0cm): HMR1098=1.19, P<0.0001; glibenclamide=1.11, P<0.0001). Similar effects were observed with hemichannel inhibitors (I(5cm)/I(0cm): meclofenamic acid=1.09, P<0.0001; probenecid=1.0, P<0.0001). The HP effect was accompanied by release of ATP (P<0.05), determined by luciferin-luciferase luminescence in perfusion solution from the luminal side of an Ussing chamber. ATP release was abrogated by both meclofenamic acid and probenecid. RT-PCR experiments revealed the expression of pannexin and connexin hemichannels and KATP subunit transcripts in X. laevis lung. These data show an activation of KATP in pulmonary epithelial cells in response to HP that is induced by ATP release through mechanosensitive pannexin and connexin hemichannels. These findings represent a novel mechanism of mechanotransduction in nonexcitable cells.

Molecular dynamics simulations highlight structural and functional alterations in deafness-related M34T mutation of connexin 26.

PubMed

Zonta, Francesco; Buratto, Damiano; Cassini, Chiara; Bortolozzi, Mario; Mammano, Fabio

2014-01-01

Mutations of the GJB2 gene encoding the connexin 26 (Cx26) gap junction protein, which is widely expressed in the inner ear, are the primary cause of hereditary non-syndromic hearing loss in several populations. The deafness-associated single amino acid substitution of methionine 34 (M34) in the first transmembrane helix (TM1) with a threonine (T) ensues in the production of mutant Cx26M34T channels that are correctly synthesized and assembled in the plasma membrane. However, mutant channels overexpressed in HeLa cells retain only 11% of the wild type unitary conductance. Here we extend and rationalize those findings by comparing wild type Cx26 (Cx26WT) and Cx26M34T mutant channels in silico, using molecular dynamics simulations. Our results indicate that the quaternary structure of the Cx26M34T hemichannel is altered at the level of the pore funnel due to the disruption of the hydrophobic interaction between M34 and tryptophan 3 (W3) in the N-terminal helix (NTH). Our simulations also show that external force stimuli applied to the NTHs can detach them from the inner wall of the pore more readily in the mutant than in the wild type hemichannel. These structural alterations significantly increase the free energy barrier encountered by permeating ions, correspondingly decreasing the unitary conductance of the Cx26M34T hemichannel. Our results accord with the proposal that the mutant resides most of the time in a low conductance state. However, the small displacement of the NTHs in our Cx26M34T hemichannel model is not compatible with the formation of a pore plug as in the related Cx26M34A mutant.

Role of Non-Myocyte Gap Junctions and Connexin Hemichannels in Cardiovascular Health and Disease: Novel Therapeutic Targets?

PubMed

Johnson, Robert D; Camelliti, Patrizia

2018-03-15

The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes. Connexins are expressed in both cardiomyocytes and non-myocytes, including cardiac fibroblasts, endothelial cells, and macrophages. Non-myocytes are the largest population of cells in the heart, and therefore it is important to consider what roles connexins, hemichannels, and gap junctions play in these cell types. The aim of this review is to provide insight into connexin-based signalling in non-myocytes during health and disease, and highlight how targeting these proteins could lead to the development of novel therapies. We conclude that connexins in non-myocytes contribute to arrhythmias and adverse ventricular remodelling following myocardial infarction, and are associated with the initiation and development of atherosclerosis. Therefore, therapeutic interventions targeting these connexins represent an exciting new research avenue with great potential.

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

PubMed Central

Bull, Cecilia; Freitas, Kelen CC; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

2014-01-01

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior. PMID:24903651

Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.

PubMed

Bull, Cecilia; Freitas, Kelen C C; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

2014-11-01

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior.

Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice.

PubMed

Szilvásy-Szabó, Anett; Varga, Edina; Beliczai, Zsuzsa; Lechan, Ronald M; Fekete, Csaba

2017-10-15

Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes. The Cx43-blocker, carbenoxolone, inhibited spreading of LY. The greatest density of Cx43-immunoreactive spots was observed in the cell membrane of α-tanycyte cell bodies. Cx43-immunoreactivity was also present in the membrane of β-tanycyte cell bodies, but in lower density. Processes of both types of tanycytes also contained Cx43-immunoreactivity. At the ultrastructural level, Cx43-immunoreactivity was present in the cell membrane of all types of tanycytes including their ventricular surface, but gap junctions were more frequent among α-tanycytes. Cx43-immunoreactivity was also observed in the cell membrane between contacting tanycyte endfeet processes, and between tanycyte endfeet process and axon varicosities in the external zone of the median eminence and capillaries in the arcuate nucleus and median eminence. These results suggest that gap junctions are present not only among tanycytes, but also between tanycytes and the axons of hypophysiotropic neurons. Cx43 hemichannels may also facilitate the transport between tanycytes and extracellular fluids, including the cerebrospinal fluid, extracellular space of the median eminence and bloodstream. Copyright © 2017 Elsevier B.V. All rights reserved.

Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

PubMed Central

Takeuchi, Hideyuki; Suzumura, Akio

2014-01-01

Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS). Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g., minocycline) have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases. PMID:25228858

On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells

PubMed Central

Vargas, Anibal A.; Cisterna, Bruno A.; Saavedra-Leiva, Fujiko; Urrutia, Carolina; Cea, Luis A.; Vielma, Alex H.; Gutierrez-Maldonado, Sebastian E.; Martin, Alberto J. M.; Pareja-Barrueto, Claudia; Escalona, Yerko; Schmachtenberg, Oliver; Lagos, Carlos F.; Perez-Acle, Tomas; Sáez, Juan C.

2017-01-01

Although connexins (Cxs) are broadly expressed by cells of mammalian organisms, Cx39 has a very restricted pattern of expression and the biophysical properties of Cx39-based channels [hemichannels (HCs) and gap junction channels (GJCs)] remain largely unknown. Here, we used HeLa cells transfected with Cx39 (HeLa-Cx39 cells) in which intercellular electrical coupling was not detected, indicating the absence of GJCs. However, functional HCs were found on the surface of cells exposed to conditions known to increase the open probability of other Cx HCs (e.g., extracellular divalent cationic-free solution (DCFS), extracellular alkaline pH, mechanical stimulus and depolarization to positive membrane potentials). Cx39 HCs were blocked by some traditional Cx HC blockers, but not by others or a pannexin1 channel blocker. HeLa-Cx39 cells showed similar resting membrane potentials (RMPs) to those of parental cells, and exposure to DCFS reduced RMPs in Cx39 transfectants, but not in parental cells. Under these conditions, unitary events of ~75 pS were frequent in HeLa-Cx39 cells and absent in parental cells. Real-time cellular uptake experiments of dyes with different physicochemical features, as well as the application of a machine-learning approach revealed that Cx39 HCs are preferentially permeable to molecules characterized by six categories of descriptors, namely: (1) electronegativity, (2) ionization potential, (3) polarizability, (4) size and geometry, (5) topological flexibility and (6) valence. However, Cx39 HCs opened by mechanical stimulation or alkaline pH were impermeable to Ca2+. Molecular modeling of Cx39-based channels suggest that a constriction present at the intracellular portion of the para helix region co-localizes with an electronegative patch, imposing an energetic and steric barrier, which in the case of GJCs may hinder channel function. Results reported here demonstrate that Cx39 form HCs and add to our understanding of the functional roles of Cx39 HCs under physiological and pathological conditions in cells that express them. PMID:28232803

Connexin channels and phospholipids: association and modulation

PubMed Central

Locke, Darren; Harris, Andrew L

2009-01-01

Background For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood. Results Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred. Conclusion This study is the first to identify (endogenous) phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents. PMID:19686581

Purinergic Signaling Regulates the Transforming Growth Factor-β3-Induced Chondrogenic Response of Mesenchymal Stem Cells to Hydrostatic Pressure.

PubMed

Steward, Andrew J; Kelly, Daniel J; Wagner, Diane R

2016-06-01

Although hydrostatic pressure (HP) is known to regulate chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs), improved insight into the mechanotransduction of HP may form the basis for novel tissue engineering strategies. Previously, we demonstrated that matrix stiffness and calcium ion (Ca(++)) mobility regulate the mechanotransduction of HP; however, the mechanisms, by which these Ca(++) signaling pathways are initiated, are currently unknown. The purinergic pathway, in which adenosine triphosphate (ATP) is released and activates P-receptors to initiate Ca(++) signaling, plays a key role in the mechanotransduction of compression, but has yet to be investigated with regard to HP. Therefore, the objective of this study was to investigate the interplay between purinergic signaling, matrix stiffness, and the chondrogenic response of MSCs to HP. Porcine bone marrow-derived MSCs were seeded into soft or stiff agarose hydrogels and subjected to HP (10 MPa at 1 Hz for 4 h/d for 21 days) or kept in free swelling conditions. Stiff constructs were incubated with pharmacological inhibitors of extracellular ATP, P2 receptors, or hemichannels, or without any inhibitors as a control. As with other loading modalities, HP significantly increased ATP release in the control group; however, inhibition of hemichannels completely abrogated this response. The increase in sulfated glycosaminoglycan (sGAG) synthesis and vimentin reorganization observed in the control group in response to HP was suppressed in the presence of all three inhibitors, suggesting that purinergic signaling is involved in the mechanoresponse of MSCs to HP. Interestingly, ATP was released from both soft and stiff hydrogels in response to HP, but HP only enhanced chondrogenesis in the stiff hydrogels, indicating that matrix stiffness may act downstream of purinergic signaling to regulate the mechanoresponse of MSCs to HP. Addition of exogenous ATP did not replicate the effects of HP on chondrogenesis, suggesting that mechanisms other than purinergic signaling also regulate the response of MSCs to HP.

Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis.

PubMed

Vaiyapuri, Sakthivel; Flora, Gagan D; Gibbins, Jonathan M

2015-06-01

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischaemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a co-ordinated manner to prevent loss of blood and control wound repair. Previous report (1) indicates that the stability and functions of a thrombus are maintained through sustained, contact-dependent signalling between platelets. Given the role of gap junctions in the co-ordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed.

Gap-junctional channel and hemichannel activity of two recently identified connexin 26 mutants associated with deafness.

PubMed

Dalamon, Viviana; Fiori, Mariana C; Figueroa, Vania A; Oliva, Carolina A; Del Rio, Rodrigo; Gonzalez, Wendy; Canan, Jonathan; Elgoyhen, Ana B; Altenberg, Guillermo A; Retamal, Mauricio A

2016-05-01

Gap-junction channels (GJCs) are formed by head-to-head association of two hemichannels (HCs, connexin hexamers). HCs and GJCs are permeable to ions and hydrophilic molecules of up to Mr ~1 kDa. Hearing impairment of genetic origin is common, and mutations of connexin 26 (Cx26) are its major cause. We recently identified two novel Cx26 mutations in hearing-impaired subjects, L10P and G109V. L10P forms functional GJCs with slightly altered voltage dependence and HCs with decrease ATP/cationic dye selectivity. G109V does not form functional GJCs, but forms functional HCs with enhanced extracellular Ca(2+) sensitivity and subtle alterations in voltage dependence and ATP/cationic dye selectivity. Deafness associated with G109V could result from decreased GJCs activity, whereas deafness associated to L10P may have a more complex mechanism that involves changes in HC permeability.

An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.

PubMed

Droguett, Karla; Rios, Mariana; Carreño, Daniela V; Navarrete, Camilo; Fuentes, Christian; Villalón, Manuel; Barrera, Nelson P

2017-07-15

Extracellular ATP, in association with [Ca 2+ ] i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement. The force exerted by cilia, measured by atomic force microscopy, is reduced following extracellular ATP hydrolysis. This result complements the current understanding of the ciliary beating regulatory mechanism, with special relevance to inflammatory diseases of the airway epithelium that affect mucociliary clearance. Extracellular nucleotides, including ATP, are locally released by the airway epithelium and stimulate ciliary activity in a [Ca 2+ ] i -dependent manner after mechanical stimulation of ciliated cells. However, it is unclear whether the ATP released is involved in regulating basal ciliary activity and mediating changes in ciliary activity in response to chemical stimulation. In the present study, we evaluated ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from mouse tracheal epithelium, using videomicroscopy and atomic force microscopy (AFM), respectively. Extracellular ATP levels and [Ca 2+ ] i were measured by luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide was measured to evaluate hemichannel functionality. We show that hydrolysis of constitutive extracellular ATP levels with apyrase (50 U ml -1 ) reduced basal CBF by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an antagonist used to block P2X7 receptors, which reduced basal CBF by 85%. Additionally, increasing extracellular ATP levels (0.1-100 μm) increased CBF, maintaining a sustained response that was suppressed in the presence of carbenoxolone. We also show that high levels of ATP (1 mm), associated with inflammatory conditions, lowered basal CBF by reducing [Ca 2+ ] i and hemichannel functionality. In summary, we provide evidence indicating that airway epithelium ATP release is the molecular autocrine mechanism regulating basal ciliary activity and is also the mediator of the ciliary response to chemical stimulation. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Evolutionary adaptation of the sensitivity of connexin26 hemichannels to CO2.

PubMed

de Wolf, Elizabeth; Cook, Jonathan; Dale, Nicholas

2017-02-08

CO 2 readily combines with H 2 O to form [Formula: see text] and H + Because an increase of only 100 nM in the concentration of H + (a decrease of 0.1 unit of pH) in blood can prove fatal, the regulated excretion of CO 2 during breathing is an essential life-preserving process. In rodents and humans, this vital process is mediated in part via the direct sensing of CO 2 via connexin26 (Cx26). CO 2 binds to hemichannels of Cx26 causing them to open and allow release of the neurotransmitter ATP. If Cx26 were to be a universal and important CO 2 sensor across all homeothermic animals, then a simple hypothesis would posit that it should exhibit evolutionary adaptation in animals with different homeostatic set points for the regulation of partial pressure of arterial CO 2 (PaCO 2 ). In humans and rats, PaCO 2 is regulated around a set point of 40 mmHg. By contrast, birds are able to maintain cerebral blood flow and breathing at much lower levels of PaCO 2 Fossorial mammals, such as the mole rat, live exclusively underground in burrows that are both hypoxic and hypercapnic and can thrive under very hypercapnic conditions. We have therefore compared the CO 2 sensitivity of Cx26 from human, chicken, rat and mole rat (Heterocephalus glaber). We find that both the affinity and cooperativity of CO 2 binding to Cx26 have been subjected to evolutionary adaption in a manner consistent with the homeostatic requirements of these four species. This is analogous to the evolutionary adaptation of haemoglobin to the needs of O 2 transport across the animal kingdom and supports the hypothesis that Cx26 is an important and universal CO 2 sensor in homeotherms. © 2017 The Authors.

Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system?

PubMed Central

De Bock, Marijke; Kerrebrouck, Marianne; Wang, Nan; Leybaert, Luc

2013-01-01

The coordination of tissue function is mediated by gap junctions (GJs) that enable direct cell–cell transfer of metabolic and electric signals. GJs are formed by connexins of which Cx43 is most widespread in the human body. In the brain, Cx43 GJs are mostly found in astroglia where they coordinate the propagation of Ca2+ waves, spatial K+ buffering, and distribution of glucose. Beyond its role in direct intercellular communication, Cx43 also forms unapposed, non-junctional hemichannels in the plasma membrane of glial cells. These allow the passage of several neuro- and gliotransmitters that may, combined with downstream paracrine signaling, complement direct GJ communication among glial cells and sustain glial-neuronal signaling. Mutations in the GJA1 gene encoding Cx43 have been identified in a rare, mostly autosomal dominant syndrome called oculodentodigital dysplasia (ODDD). ODDD patients display a pleiotropic phenotype reflected by eye, hand, teeth, and foot abnormalities, as well as craniofacial and bone malformations. Remarkably, neurological symptoms such as dysarthria, neurogenic bladder (manifested as urinary incontinence), spasticity or muscle weakness, ataxia, and epilepsy are other prominent features observed in ODDD patients. Over 10 mutations detected in patients diagnosed with neurological disorders are associated with altered functionality of Cx43 GJs/hemichannels, but the link between ODDD-related abnormal channel activities and neurologic phenotype is still elusive. Here, we present an overview on the nature of the mutants conveying structural and functional changes of Cx43 channels and discuss available evidence for aberrant Cx43 GJ and hemichannel function. In a final step, we examine the possibilities of how channel dysfunction may lead to some of the neurological manifestations of ODDD. PMID:24133447

Analysis of four connexin26 mutant gap junctions and hemichannels reveals variations in hexamer stability.

PubMed

Ambrosi, Cinzia; Boassa, Daniela; Pranskevich, Jennifer; Smock, Amy; Oshima, Atsunori; Xu, Ji; Nicholson, Bruce J; Sosinsky, Gina E

2010-05-19

Connexin26 is a ubiquitous gap junction protein that serves critical homeostatic functions. Four single-site mutations found in the transmembrane helices (M1-M4) cause different types of dysfunctional channels: 1), Cx26T135A in M3 produces a closed channel; 2), Cx26M34A in M1 severely decreases channel activity; 3), Cx26P87L in M2 has been implicated in defective channel gating; and 4), Cx26V84L in M2, a nonsyndromic deafness mutant, retains normal dye coupling and electrophysiological properties but is deficient in IP(3) transfer. These mutations do not affect Cx26 trafficking in mammalian cells, and make normal-appearing channels in baculovirus-infected Sf9 membranes when imaged by negative stain electron microscopy. Upon dodecylmaltoside solubilization of the membrane fraction, Cx26M34A and Cx26V84L are stable as hexamers or dodecamers, but Cx26T135A and Cx26P87L oligomers are not. This instability is also found in Cx26T135A and Cx26P87L hemichannels isolated from mammalian cells. In this work, coexpression of both wild-type Cx26 and Cx26P87L in Sf9 cells rescued P87L hexamer stability. Similarly, in paired Xenopus oocytes, coexpression with wild-type restored function. In contrast, the stability of Cx26T135A hemichannels could not be rescued by coexpression with WT. Thus, T135 and P87 residues are in positions that are important for oligomer stability and can affect gap junction gating. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Osteogenic differentiation capacity of human mesenchymal stromal cells in response to extracellular calcium with special regard to connexin 43.

PubMed

Wagner, Alena-Svenja; Glenske, Kristina; Wolf, Verena; Fietz, Daniela; Mazurek, Sybille; Hanke, Thomas; Moritz, Andreas; Arnhold, Stefan; Wenisch, Sabine

2017-01-01

The effects of extracellular calcium on osteogenic differentiation capacity of human bone-derived mesenchymal stromal cells with special regard to connexin 43 (cx43) have been investigated by means of cell culture experiments. Mesenchymal stromal cells isolated from human cancellous bone were cultured on tissue culture plates at different calcium ion (Ca 2+ ) concentrations (1.8mmoll -1 , 10mmoll -1 , 20mmoll -1 ). Cell responses were evaluated by quantitative RT-PCR, immunofluorescence staining, and Lucifer Yellow fluorescence uptake experiments. It could be shown that increasing Ca 2+ concentrations correlate with increasing cx43 and bone sialoprotein mRNA levels as well as with enhanced cx43 fluorescence signaling and matrix mineralization of the cultures as shown by von Kossa staining. Hemichannel gating - assessed by Lucifer Yellow uptake - increases with increasing extracellular Ca 2+ concentrations suggesting that regulatory effects at the hemichannel level are calcium-dependent. Copyright © 2016 Elsevier GmbH. All rights reserved.

Inhibition of Connexin43 Hemichannels Impairs Spatial Short-Term Memory without Affecting Spatial Working Memory.

PubMed

Walrave, Laura; Vinken, Mathieu; Albertini, Giulia; De Bundel, Dimitri; Leybaert, Luc; Smolders, Ilse J

2016-01-01

Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs). We here investigated whether interfering with connexin43 (Cx43) HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19) into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle

PubMed Central

Shestopalov, Valery I.; Panchin, Yuri; Tarasova, Olga S.; Gaynullina, Dina; Kovalzon, Vladimir M.

2017-01-01

During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1−/− mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx) in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Panx in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle. PMID:28769767

Pannexins Are Potential New Players in the Regulation of Cerebral Homeostasis during Sleep-Wake Cycle.

PubMed

Shestopalov, Valery I; Panchin, Yuri; Tarasova, Olga S; Gaynullina, Dina; Kovalzon, Vladimir M

2017-01-01

During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin-1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1 -/- mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of pannexins (Panx) in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Panx in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle.

ATP Releasing Connexin 30 Hemichannels Mediate Flow-Induced Calcium Signaling in the Collecting Duct

PubMed Central

Svenningsen, Per; Burford, James L.; Peti-Peterdi, János

2013-01-01

ATP in the renal tubular fluid is an important regulator of salt and water reabsorption via purinergic calcium signaling that involves the P2Y2 receptor, ENaC, and AQP2. Recently, we have shown that connexin (Cx) 30 hemichannels are localized to the non-junctional apical membrane of cells in the distal nephron-collecting duct (CD) and release ATP into the tubular fluid upon mechanical stimuli, leading to reduced salt and water reabsorption. Cx30−/− mice show salt-dependent elevations in BP and impaired pressure-natriuresis. Thus, we hypothesized that increased tubular flow rate leads to Cx30-dependent purinergic intracellular calcium ([Ca2+]i) signaling in the CD. Cortical CDs (CCDs) from wild type and Cx30−/− mice were freshly dissected and microperfused in vitro. Using confocal fluorescence imaging and the calcium-sensitive fluorophore pair Fluo-4 and Fura Red, we found that increasing tubular flow rate from 2 to 20 nl/min caused a significant 2.1-fold elevation in [Ca2+]i in wild type CCDs. This response was blunted in Cx30−/− CCDs ([Ca2+]i increased only 1.2-fold, p < 0.0001 vs. WT, n = 6 each). To further test our hypothesis we performed CD [Ca2+]i imaging in intact mouse kidneys in vivo using multiphoton microscopy and micropuncture delivery of the calcium-sensitive fluorophore Rhod-2. We found intrinsic, spontaneous [Ca2+]i oscillations in free-flowing CDs of wild type but not Cx30−/− mice. The [Ca2+]i oscillations were sensitive also to P2-receptor inhibition by suramin. Taken together, these data confirm that mechanosensitive Cx30 hemichannels mediate tubular ATP release and purinergic calcium signaling in the CD which mechanism plays an important role in the regulation of CD salt and water reabsorption. PMID:24137132

Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Müller cells, lens, trabecular meshwork, cornea and lacrimal gland

PubMed Central

Sanderson, Julie; Dartt, Darlene A.; Trinkaus-Randall, Vickery; Pintor, Jesus; Civan, Mortimer M.; Delamere, Nicholas A.; Fletcher, Erica L.; Salt, Thomas E.; Grosche, Antje; Mitchell, Claire H.

2014-01-01

This review highlights recent findings that describe how purines modulate the physiological and pathophysiological responses of ocular tissues. For example, in lacrimal glands the cross-talk between P2X7 receptors and both M3 muscarinic receptors and α1D-adrenergic receptors can influence tear secretion. In the cornea, purines lead to post-translational modification of EGFR and structural proteins that participate in wound repair in the epithelium and influence the expression of matrix proteins in the stroma. Purines act at receptors on both the trabecular meshwork and ciliary epithelium to modulate intraocular pressure (IOP); ATP-release pathways of inflow and outflow cells differ, possibly permitting differential modulation of adenosine delivery. Modulators of trabecular meshwork cell ATP release include cell volume, stretch, extracellular Ca2+ concentration, oxidation state, actin remodeling and possibly endogenous cardiotonic steroids. In the lens, osmotic stress leads to ATP release following TRPV4 activation upstream of hemichannel opening. In the anterior eye, diadenosine polyphosphates such as Ap4A act at P2 receptors to modulate the rate and composition of tear secretion, impact corneal wound healing and lower IOP. The Gq11-coupled P2Y1-receptor contributes to volume control in Müller cells and thus the retina. P2X receptors are expressed in neurons in the inner and outer retina and contribute to visual processing as well as the demise of retinal ganglion cells. In RPE cells, the balance between extracellular ATP and adenosine may modulate lysosomal pH and the rate of lipofuscin formation. In optic nerve head astrocytes, mechanosensitive ATP release via pannexin hemichannels, coupled with stretch-dependent upregulation of pannexins, provides a mechanism for ATP signaling in chronic glaucoma. With so many receptors linked to divergent functions throughout the eye, ensuring the transmitters remain local and stimulation is restricted to the intended target may be a key issue in understanding how physiological signaling becomes pathological in ocular disease. PMID:25151301

Shigella gets captured to gain entry.

PubMed

McCormick, Beth A

2011-06-16

The type III secretion system-dependent epithelial invasion and dissemination of Shigella is stimulated by ATP released through hemichannels. Romero et al. (2011) show that prior to epithelial contact, Shigella is captured by nanometer-thin micropodial extensions at a distance from the cell surface, in a process involving ATP and connexin-mediated signaling. Copyright © 2011 Elsevier Inc. All rights reserved.

A Co-operative Regulation of Neuronal Excitability by UNC-7 Innexin and NCA/NALCN Leak Channel

PubMed Central

2011-01-01

Gap junctions mediate the electrical coupling and intercellular communication between neighboring cells. Some gap junction proteins, namely connexins and pannexins in vertebrates, and innexins in invertebrates, may also function as hemichannels. A conserved NCA/Dmα1U/NALCN family cation leak channel regulates the excitability and activity of vertebrate and invertebrate neurons. In the present study, we describe a genetic and functional interaction between the innexin UNC-7 and the cation leak channel NCA in Caenorhabditis elegans neurons. While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response. The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions. We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels. PMID:21489288

Hexadecameric structure of an invertebrate gap junction channel.

PubMed

Oshima, Atsunori; Matsuzawa, Tomohiro; Murata, Kazuyoshi; Tani, Kazutoshi; Fujiyoshi, Yoshinori

2016-03-27

Innexins are invertebrate-specific gap junction proteins with four transmembrane helices. These proteins oligomerize to constitute intercellular channels that allow for the passage of small signaling molecules associated with neural and muscular electrical activity. In contrast to the large number of structural and functional studies of connexin gap junction channels, few structural studies of recombinant innexin channels are reported. Here we show the three-dimensional structure of two-dimensionally crystallized Caenorhabditis elegans innexin-6 (INX-6) gap junction channels. The N-terminal deleted INX-6 proteins are crystallized in lipid bilayers. The three-dimensional reconstruction determined by cryo-electron crystallography reveals that a single INX-6 gap junction channel comprises 16 subunits, a hexadecamer, in contrast to chordate connexin channels, which comprise 12 subunits. The channel pore diameters at the cytoplasmic entrance and extracellular gap region are larger than those of connexin26. Two bulb densities are observed in each hemichannel, one in the pore and the other at the cytoplasmic side of the hemichannel in the channel pore pathway. These findings imply a structural diversity of gap junction channels among multicellular organisms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Extracellular domains play different roles in gap junction formation and docking compatibility.

PubMed

Bai, Donglin; Wang, Ao Hong

2014-02-15

GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels dock together end-to-end to form a GJ channel. Connexin extracellular domains (E1 and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that E1 and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the E1 domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both E1 and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.

Results of the Round Robin on opening-load measurement conducted by ASTM Task Group E24.04.04 on Crack Closure Measurement and Analysis

NASA Technical Reports Server (NTRS)

Phillips, Edward P.

1989-01-01

An experimental Round Robin on the measurement of the opening load in fatigue crack growth tests was conducted on Crack Closure Measurement and Analysis. The Round Robin evaluated the current level of consistency of opening load measurements among laboratories and to identify causes for observed inconsistency. Eleven laboratories participated in the testing of compact and middle-crack specimens. Opening-load measurements were made for crack growth at two stress-intensity factor levels, three crack lengths, and following an overload. All opening-load measurements were based on the analysis of specimen compliance data. When all of the results reported (from all participants, all measurement methods, and all data analysis methods) for a given test condition were pooled, the range of opening loads was very large--typically spanning the lower half of the fatigue loading cycle. Part of the large scatter in the reported opening-load results was ascribed to consistent differences in results produced by the various methods used to measure specimen compliance and to evaluate the opening load from the compliance data. Another significant portion of the scatter was ascribed to lab-to-lab differences in producing the compliance data when using nominally the same method of measurement.

Results of the second Round Robin on opening-load measurement conducted by ASTM Task Group E24.04.04 on crack closure measurement and analysis

NASA Technical Reports Server (NTRS)

Phillips, E. P.

1993-01-01

A second experimental Round Robin on the measurement of the crack opening load in fatigue crack growth tests has been completed by the ASTM Task Group E24.04.04 on Crack Closure Measurement and Analysis. Fourteen laboratories participated in the testing of aluminum alloy compact tension specimens. Opening-load measurements were made at three crack lengths during constant Delta K, constant stress ratio tests by most of the participants. Four participants made opening-load measurements during threshold tests. All opening-load measurements were based on the analysis of specimens compliance behavior, where the displacement/strain was measured either at the crack mouth or the mid-height back face location. The Round Robin data were analyzed for opening load using two non-subjective analysis methods: the compliance offset and the correlation coefficient methods. The scatter in the opening load results was significantly reduced when some of the results were excluded from the analysis population based on an accept/reject criterion for raw data quality. The compliance offset and correlation coefficient opening load analysis methods produced similar results for data populations that had been screened to eliminate poor quality data.

Ca2+ signaling in injured in situ endothelium of rat aorta.

PubMed

Berra-Romani, Roberto; Raqeeb, Abdul; Avelino-Cruz, José Everardo; Moccia, Francesco; Oldani, Amanda; Speroni, Francisco; Taglietti, Vanni; Tanzi, Franco

2008-09-01

The inner wall of excised rat aorta was scraped by a microelectrode and Ca2+ signals were investigated by fluorescence microscopy in endothelial cells (ECs) directly coupled with injured cells. The injury caused an immediate increase in the intracellular Ca2+ concentration ([Ca2+]i), followed by a long-lasting decay phase due to Ca2+ influx from extracellular space. The immediate response was mainly due to activation of purinergic receptors, as shown by the effect of P2X and P2Y receptors agonists and antagonists, such as suramin, alpha,beta-MeATP, MRS-2179 and 2-MeSAMP. Inhibition of store-operated Ca2+ influx did not affect either the peak response or the decay phase. Furthermore, the latter was: (i) insensitive to phospholipase C inhibition, (ii) sensitive to the gap junction blockers, palmitoleic acid, heptanol, octanol and oleamide, and (iii) sensitive to La3+ and Ni2+, but not to Gd3+. Finally, ethidium bromide or Lucifer Yellow did not enter ECs facing the scraped area. These results suggest that endothelium scraping: (i) causes a short-lasting stimulation of healthy ECs by extracellular nucleotides released from damaged cells and (ii) uncouples the hemichannels of the ECs facing the injury site; these hemichannels do not fully close and allow a long-lasting Ca2+ entry.

Possible involvement of TLRs and hemichannels in stress-induced CNS dysfunction via mastocytes, and glia activation.

PubMed

Aguirre, Adam; Maturana, Carola J; Harcha, Paloma A; Sáez, Juan C

2013-01-01

In the central nervous system (CNS), mastocytes and glial cells (microglia, astrocytes and oligodendrocytes) function as sensors of neuroinflammatory conditions, responding to stress triggers or becoming sensitized to subsequent proinflammatory challenges. The corticotropin-releasing hormone and glucocorticoids are critical players in stress-induced mastocyte degranulation and potentiation of glial inflammatory responses, respectively. Mastocytes and glial cells express different toll-like receptor (TLR) family members, and their activation via proinflammatory molecules can increase the expression of connexin hemichannels and pannexin channels in glial cells. These membrane pores are oligohexamers of the corresponding protein subunits located in the cell surface. They allow ATP release and Ca(2+) influx, which are two important elements of inflammation. Consequently, activated microglia and astrocytes release ATP and glutamate, affecting myelinization, neuronal development, and survival. Binding of ligands to TLRs induces a cascade of intracellular events leading to activation of several transcription factors that regulate the expression of many genes involved in inflammation. During pregnancy, the previous responses promoted by viral infections and other proinflammatory conditions are common and might predispose the offspring to develop psychiatric disorders and neurological diseases. Such disorders could eventually be potentiated by stress and might be part of the etiopathogenesis of CNS dysfunctions including autism spectrum disorders and schizophrenia.

Boldine Prevents Renal Alterations in Diabetic Rats

PubMed Central

Hernández-Salinas, Romina; Vielma, Alejandra Z.; Arismendi, Marlene N.; Boric, Mauricio P.; Sáez, Juan C.; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects. PMID:24416726

Boldine prevents renal alterations in diabetic rats.

PubMed

Hernández-Salinas, Romina; Vielma, Alejandra Z; Arismendi, Marlene N; Boric, Mauricio P; Sáez, Juan C; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects.

[Octanol preconditioning alleviates mouse cardiomyocyte swelling induced by simulated ischemia/reperfusion challenge in vitro].

PubMed

Luo, Yukun; Fang, Jun; Fan, Lin; Lin, Chaogui; Chen, Zhaoyang; Chen, Lianglong

2012-10-01

To investigate the role of connexin 43-formed hemichannels in cell volume regulation induced by simulated ischemia/reperfusion (SI/R). Mouse cardiomyocytes isolated on a Langendorff apparatus with enzyme solution were aliquoted into control, SI/R and SI/R +octanol groups. Calcein-AM was used to stain the cells and the cell volume was measured with confocal microscope by stack scanning. Trypan blue was used to measure the cell viability after the treatments. Calcein-AM staining and cofocal microscopy yielded stable and reproducible results for cell volume measurement. Mouse cardiomyocytes subjected to simulated SI/R showed obvious cell swelling as compared with the control cells [(126∓6)% vs 100%, P<0.05], and octanol preconditioning significantly attenuated the cell swelling [(113∓6)%, P<0.05]. SI/R caused a significant reduction of the cell viability compared to the control cells [(19∓2)% vs (45∓3)%, P<0.01], and octanol preconditioning obviously reduced the viability of the cells with SI/R challenge [(31∓2)%, P<0.01]. Connexin 43-formed hemichannels are involved in the regulation of cardiomyocyte volumes induced by SI/R challenge, and octanol can alleviate the cell swelling to enhance the viability of the cardiomyocytes following SI/R.

Research on virtual network load balancing based on OpenFlow

NASA Astrophysics Data System (ADS)

Peng, Rong; Ding, Lei

2017-08-01

The Network based on OpenFlow technology separate the control module and data forwarding module. Global deployment of load balancing strategy through network view of control plane is fast and of high efficiency. This paper proposes a Weighted Round-Robin Scheduling algorithm for virtual network and a load balancing plan for server load based on OpenFlow. Load of service nodes and load balancing tasks distribution algorithm will be taken into account.

Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: insights into syndromic hearing loss

PubMed Central

Sanchez, Helmuth A.; Verselis, Vytas K.

2014-01-01

Mutation of the GJB2 gene, which encodes the connexin 26 (Cx26) gap junction (GJ) protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26 is not expressed in hair cells, but is widely expressed throughout the non-sensory epithelial cells of the cochlea. Most GJB2 mutations produce non-syndromic deafness, but a subset produces syndromic deafness in which profound hearing loss is accompanied by a diverse array of infectious and neoplastic cutaneous disorders that can be fatal. Although GJ channels, which are assembled by the docking of two, so-called hemichannels (HCs), have been the main focus of deafness-associated disease models, it is now evident that the HCs themselves can function in the absence of docking and contribute to signaling across the cell membrane as a novel class of ion channel. A notable feature of syndromic deafness mutants is that the HCs exhibit aberrant behaviors providing a plausible basis for disease that is associated with excessive or altered contributions of Cx26 HCs that, in turn, lead to compromised cell integrity. Here we discuss some of the aberrant Cx26 HC properties that have been described for mutants associated with keratitis-ichthyosis-deafness (KID) syndrome, a particularly severe Cx26-associated syndrome, which shed light on genotype-phenotype relationships and causes underlying cochlear dysfunction. PMID:25386120

Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

PubMed Central

Schulz, Rainer; Görge, Philipp Maximilian; Görbe, Anikó; Ferdinandy, Péter; Lampe, Paul D.; Leybaert, Luc

2015-01-01

Connexins are widely distributed proteins in the body that are crucially important for heart and brain function. Six connexin subunits form a connexon or hemichannel in the plasma membrane. Interactions between two hemichannels in a head-to-head arrangement result in the formation of a gap junction channel. Gap junctions are necessary to coordinate cell function by passing electrical current flow between heart and nerve cells or by allowing exchange of chemical signals and energy substrates. Apart from its localisation at the sarcolemma of cardiomyocytes and brain cells, connexins are also found in mitochondria where they are involved in the regulation of mitochondrial matrix ion fluxes and respiration. Connexin expression is affected by age and gender as well as several pathophysiological alterations such as hypertension, hypertrophy, diabetes, hypercholesterolemia, ischemia, post-myocardial infarction remodelling or heart failure, and post-translationally connexins are modified by phosphorylation/de-phosphorylation and nitros(yl)ation which can modulate channel activity. Using knockout/knockin technology as well as pharmacological approaches, one of the connexins, namely connexin 43, has been identified to be important for cardiac and brain ischemia/reperfusion injury as well as protection from it. Therefore, the current review will focus on the importance of connexin 43 for irreversible injury of heart and brain tissue following ischemia/reperfusion and will highlight the importance of connexin 43 as an emerging therapeutic target in cardio- and neuroprotection. PMID:26073311

Structural analysis of key gap junction domains--Lessons from genome data and disease-linked mutants.

PubMed

Bai, Donglin

2016-02-01

A gap junction (GJ) channel is formed by docking of two GJ hemichannels and each of these hemichannels is a hexamer of connexins. All connexin genes have been identified in human, mouse, and rat genomes and their homologous genes in many other vertebrates are available in public databases. The protein sequences of these connexins align well with high sequence identity in the same connexin across different species. Domains in closely related connexins and several residues in all known connexins are also well-conserved. These conserved residues form signatures (also known as sequence logos) in these domains and are likely to play important biological functions. In this review, the sequence logos of individual connexins, groups of connexins with common ancestors, and all connexins are analyzed to visualize natural evolutionary variations and the hot spots for human disease-linked mutations. Several gap junction domains are homologous, likely forming similar structures essential for their function. The availability of a high resolution Cx26 GJ structure and the subsequently-derived homology structure models for other connexin GJ channels elevated our understanding of sequence logos at the three-dimensional GJ structure level, thus facilitating the understanding of how disease-linked connexin mutants might impair GJ structure and function. This knowledge will enable the design of complementary variants to rescue disease-linked mutants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estimation of joint stiffness with a compliant load.

PubMed

Ludvig, Daniel; Kearney, Robert E

2009-01-01

Joint stiffness defines the dynamic relationship between the position of the joint and the torque acting about it. It consists of two components: intrinsic and reflex stiffness. Many previous studies have investigated joint stiffness in an open-loop environment, because the current algorithm in use is an open-loop algorithm. This paper explores issues related to the estimation of joint stiffness when subjects interact with compliant loads. First, we show analytically how the bias in closed-loop estimates of joint stiffness depends on the properties of the load, the noise power, and length of the estimated impulse response functions (IRF). We then demonstrate with simulations that the open-loop analysis will fail completely for an elastic load but may succeed for an inertial load. We further show that the open-loop analysis can yield unbiased results with an inertial load and document IRF length, signal-to-noise ratio needed, and minimum inertia needed for the analysis to succeed. Thus, by using a load with a properly selected inertia, open-loop analysis can be used under closed-loop conditions.

A Kind of Optimization Method of Loading Documents in OpenOffice.org

NASA Astrophysics Data System (ADS)

Lan, Yuqing; Li, Li; Zhou, Wenbin

As a giant in open source community, OpenOffice.org has become the most popular office suite within Linux community. But OpenOffice.org is relatively slow while loading documents. Research shows that the most time consuming part is importing one page of whole document. If there are many pages in a document, the accumulation of time consumed can be astonishing. Therefore, this paper proposes a solution, which has improved the speed of loading documents through asynchronous importing mechanism: a document is not imported as a whole, but only part of the document is imported at first for display, then mechanism in the background is started to asynchronously import the remaining parts, and insert it into the drawing queue of OpenOffice.org for display. In this way, the problem can be solved and users don't have to wait for a long time. Application start-up time testing tool has been used to test the time consumed in loading different pages of documents before and after optimization of OpenOffice.org, then, we adopt the regression theory to analyse the correlation between the page number of documents and the loading time. In addition, visual modeling of the experimental data are acquired with the aid of matlab. An obvious increase in loading speed can be seen after a comparison of the time consumed to load a document before and after the solution is adopted. And then, using Microsoft Office compared with the optimized OpenOffice.org, their loading speeds are almost same. The results of the experiments show the effectiveness of this solution.

Transforming Growth Factor Beta 1 Drives a Switch in Connexin Mediated Cell-to-Cell Communication in Tubular Cells of the Diabetic Kidney.

PubMed

Hills, Claire; Price, Gareth William; Wall, Mark John; Kaufmann, Timothy John; Chi-Wai Tang, Sidney; Yiu, Wai Han; Squires, Paul Edward

2018-01-01

Changes in cell-to-cell communication have been linked to several secondary complications of diabetes, but the mechanism by which connexins affect disease progression in the kidney is poorly understood. This study examines a role for glucose-evoked changes in the beta1 isoform of transforming growth factor (TGFβ1), on connexin expression, gap-junction mediated intercellular communication (GJIC) and hemi-channel ATP release from tubular epithelial cells of the proximal renal nephron. Biopsy material from patients with and without diabetic nephropathy was stained for connexin-26 (CX26) and connexin-43 (CX43). Changes in expression were corroborated by immunoblot analysis in human primary proximal tubule epithelial cells (hPTECs) and model epithelial cells from human renal proximal tubules (HK2) cultured in either low glucose (5mmol/L) ± TGFβ1 (2-10ng/ml) or high glucose (25mmol/L) for 48h or 7days. Secretion of the cytokine was determined by ELISA. Paired whole cell patch clamp recordings were used to measure junctional conductance in control versus TGFβ1 treated (10ng/ml) HK2 cells, with carboxyfluorescein uptake and ATP-biosensing assessing hemi-channel function. A downstream role for ATP in mediating the effects of TGF-β1 on connexin mediated cell communication was assessed by incubating cells with ATPγS (1-100µM) or TGF-β1 +/- apyrase (5 Units/ml). Implications of ATP release were measured through immunoblot analysis of interleukin 6 (IL-6) and fibronectin expression. Biopsy material from patients with diabetic nephropathy exhibited increased tubular expression of CX26 and CX43 (P<0.01, n=10), data corroborated in HK2 and hPTEC cells cultured in TGFβ1 (10ng/ml) for 7days (P<0.001, n=3). High glucose significantly increased TGFβ1 secretion from tubular epithelial cells (P<0.001, n=3). The cytokine (10ng/ml) reduced junctional conductance between HK2 cells from 4.5±1.3nS in control to 1.15±0.9nS following 48h TGFβ1 and to 0.42±0.2nS after 7days TGFβ1 incubation (P<0.05, n=5). Acute (48h) and chronic (7day) challenge with TGFβ1 produced a carbenoxolone (200µM)-sensitive increase in carboxyfluorescein loading, matched by an increase in ATP release from 0.29±0.06μM in control to 1.99±0.47μM after 48hr incubation with TGFβ1 (10ng/ml; P<0.05, n=3). TGF-β1 (2-10ng/ml) and ATPγs (1-100µM) increased expression of IL-6 (P<0.001 n=3) and fibronectin (P<0.01 n=3). The effect of TGF-β1 on IL-6 and fibronectin expression was partially blunted when preincubated with apyrase (n=3). These data suggest that chronic exposure to glucose-evoked TGFβ1 induce an increase in CX26 and CX43 expression, consistent with changes observed in tubular epithelia from patients with diabetic nephropathy. Despite increased connexin expression, direct GJIC communication decreases, whilst hemichannel expression/function and paracrine release of ATP increases, changes that trigger increased levels of expression of interleukin 6 and fibronectin. Linked to inflammation and fibrosis, local increases in purinergic signals may exacerbate disease progression and highlight connexin mediated cell communication as a future therapeutic target for diabetic nephropathy. © 2018 The Author(s). Published by S. Karger AG, Basel.

Series-counterpulse repetitive-pulse inductive storage circuit

DOEpatents

Honig, E.M.

1984-06-05

A high-power series-counterpulse repetitive-pulse inductive energy storage and transfer circuit includes an opening switch, a main energy storage coil, and a counterpulse capacitor. The local pulse is initiated simultaneously with the initiation of the counterpulse used to turn the opening switch off. There is no delay from command to output pulse. During the load pulse, the counterpulse capacitor is automatically charged with sufficient energy to accomplish the load counterpulse which terminates the load pulse and turns the load switch off. When the main opening switch is reclosed to terminate the load pulse, the counterpulse capacitor discharges through the load, causing a rapid, sharp cutoff of the load pulse as well as recovering any energy remaining in the load inductance. The counterpulse capacitor is recharged to its original condition by the main energy storage coil after the load pulse is over, not before it begins.

46 CFR 45.143 - Hull openings above freeboard deck.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Hull openings above freeboard deck. 45.143 Section 45.143 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Conditions of Assignment § 45.143 Hull openings above freeboard deck. Closures for openings above...

Series-counterpulse repetitive-pulse inductive storage circuit

DOEpatents

Honig, Emanuel M.

1986-01-01

A high-power series-counterpulse repetitive-pulse inductive energy storage and transfer circuit includes an opening switch, a main energy storage coil, and a counterpulse capacitor. The load pulse is initiated simultaneously with the initiation of the counterpulse which is used to turn the opening switch off. There is no delay from command to output pulse. During the load pulse, the counterpulse capacitor is first discharged and then recharged in the opposite polarity with sufficient energy to accomplish the load counterpulse which terminates the load pulse and turns the load switch off. When the main opening switch is triggered closed again to terminate the load pulse, the counterpulse capacitor discharges in the reverse direction through the load switch and through the load, causing a rapid, sharp cutoff of the load pulse as well as recovering any energy remaining in the load inductance. The counterpulse capacitor is recharged to its original condition by the main energy storage coil after the load pulse is over, not before it begins.

Non-syndromic hearing loss caused by the dominant cis mutation R75Q with the recessive mutation V37I of the GJB2 (Connexin 26) gene.

PubMed

Kim, Juwon; Jung, Jinsei; Lee, Min Goo; Choi, Jae Young; Lee, Kyung-A

2015-06-19

GJB2 alleles containing two cis mutations have been rarely found in non-syndromic hearing loss. Herein, we present a Korean patient with non-syndromic hearing loss caused by the R75Q cis mutation with V37I, which arose de novo in the father and was inherited by the patient. Biochemical coupling and hemichannel permeability assays were performed after molecular cloning and transfection of HEK293T cells. Student's t-tests or analysis of variance followed by Tukey's multiple comparison test was used as statistical analysis. Biochemical coupling was significantly reduced in connexin 26 (Cx26)-R75Q- and Cx26-V37I-transfected cells, with greater extent in Cx26-R75Q and Cx26-R75Q+V37I cells. Interestingly, our patient and his father with the mutations had more residual hearing compared with patients with the dominant mutation alone. Although the difference in hemichannel activity between R75Q alone and R75Q in combination with V37I failed to reach significance, it is of note that there is a possibility that V37I located upstream of R75Q might have the ability to ameliorate R75Q expression. Our study emphasizes the importance of cis mutations with R75Q, as the gene effect of R75Q can be modulated depending on the type of additional mutation.

Limits to Open Class Performance?

NASA Technical Reports Server (NTRS)

Bowers, Albion H.

2008-01-01

This presentation discusses open or unlimited class aircraft performance limitations and design solutions. Limitations in this class of aircraft include slow climbing flight which requires low wing loading, high cruise speed which requires high wing loading, gains in induced or viscous drag alone which result in only half the gain overall and other structural problems (yaw inertia and spins, flutter and static loads integrity). Design solutions include introducing minimum induced drag for a given span (elliptical span load or winglets) and introducing minimum induced drag for a bell shaped span load. It is concluded that open class performance limits (under current rules and technologies) is very close to absolute limits, though some gains remain to be made from unexplored areas and new technologies.

29 CFR 1926.751 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... process of erection. Steel joist means an open web, secondary load-carrying member of 144 feet (43.9 m) or... structural steel trusses or cold-formed joists. Steel joist girder means an open web, primary load-carrying... structural steel trusses. Steel truss means an open web member designed of structural steel components by the...

29 CFR 1926.751 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... process of erection. Steel joist means an open web, secondary load-carrying member of 144 feet (43.9 m) or... structural steel trusses or cold-formed joists. Steel joist girder means an open web, primary load-carrying... structural steel trusses. Steel truss means an open web member designed of structural steel components by the...

Open-mouthed hybrid microcapsules with elevated enzyme loading and enhanced catalytic activity.

PubMed

Shi, Jiafu; Zhang, Shaohua; Wang, Xiaoli; Jiang, Zhongyi

2014-10-25

Open-mouthed hybrid microcapsules (HMCs) are synthesized through a hard-templating method. When utilized for enzyme immobilization and enzymatic catalysis, the open-mouthed HMCs show high enzyme loading capability, enhanced catalytic activity and desirable recycling stability, due to their fully exposed outer and inner surfaces.

49 CFR 174.101 - Loading Class 1 (explosive) materials.

Code of Federal Regulations, 2014 CFR

2014-10-01

... in a rail car equipped with any type of lighted heater or open-flame device, or electric devices... stock cars or in flat bottom gondola cars only if they are adequately braced. Boxed bombs, rocket... be loaded in closed cars, may be loaded in open-top cars or on flatcars, provided they are protected...

49 CFR 174.101 - Loading Class 1 (explosive) materials.

Code of Federal Regulations, 2012 CFR

2012-10-01

... in a rail car equipped with any type of lighted heater or open-flame device, or electric devices... stock cars or in flat bottom gondola cars only if they are adequately braced. Boxed bombs, rocket... be loaded in closed cars, may be loaded in open-top cars or on flatcars, provided they are protected...

49 CFR 174.101 - Loading Class 1 (explosive) materials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... in a rail car equipped with any type of lighted heater or open-flame device, or electric devices... stock cars or in flat bottom gondola cars only if they are adequately braced. Boxed bombs, rocket... be loaded in closed cars, may be loaded in open-top cars or on flatcars, provided they are protected...

49 CFR 174.101 - Loading Class 1 (explosive) materials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... in a rail car equipped with any type of lighted heater or open-flame device, or electric devices... stock cars or in flat bottom gondola cars only if they are adequately braced. Boxed bombs, rocket... be loaded in closed cars, may be loaded in open-top cars or on flatcars, provided they are protected...

Fatigue crack growth with single overload - Measurement and modeling

NASA Technical Reports Server (NTRS)

Davidson, D. L.; Hudak, S. J., Jr.; Dexter, R. J.

1987-01-01

This paper compares experiments with an analytical model of fatigue crack growth under variable amplitude. The stereoimaging technique was used to measure displacements near the tips of fatigue cracks undergoing simple variations in load amplitude-single overloads and overload/underload combinations. Measured displacements were used to compute strains, and stresses were determined from the strains. Local values of crack driving force (Delta-K effective) were determined using both locally measured opening loads and crack tip opening displacements. Experimental results were compared with simulations made for the same load variation conditions using Newman's FAST-2 model. Residual stresses caused by overloads, crack opening loads, and growth retardation periods were compared.

Ca2+ Responses in Enteric Glia are Mediated by Connexin-43 Hemichannels and Modulate Colonic Transit in Mice

PubMed Central

Fried, David; Gomez-Suarez, Roberto A.; Leinninger, Gina M.; Sévigny, Jean; Parpura, Vladimir; Gulbransen, Brian D.

2014-01-01

Background & Aims In the enteric nervous system, neurotransmitters initiate changes in Ca2+ (Ca2+ responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca2+-mediated responses in enteric glial are required to maintain gastrointestinal function. Methods We used in situ Ca2+ imaging to monitor glial Ca2+ responses, which were manipulated with pharmacologic agents or via glia-specific disruption of the gene encoding connexin-43 (Cx43) (hGFAP::creERT2+/−/Cx43f/f mice). Gastrointestinal function was assessed based on pellet output, total gut transit, colonic bead expulsion, and muscle tension recordings. Proteins were localized and quantified by immunohistochemistry, immunoblot, and reverse transcription PCR analyses. Results Ca2+ responses in enteric glia of mice were mediated by Cx43 hemichannels. Cx43 immunoreactivity was confined to enteric glia within the myenteric plexus of the mouse colon; the Cx43 inhibitors carbenoxolone and 43Gap26 inhibited the ability of enteric glia to propagate Ca2+ responses. In vivo attenuation of Ca2+ responses in the enteric glial network slowed gut transit overall and delayed colonic transit—these changes are also observed during normal aging. Altered motility with increasing age was associated with reduced glial Ca2+-mediated responses and changes in glial expression of Cx43 mRNA and protein. Conclusions Ca2+-mediated responses in enteric glia regulate gastrointestinal function in mice. Altered intercellular signaling between enteric glia and neurons might contribute to motility disorders. PMID:24211490

Autocrine Regulation of UVA-Induced IL-6 Production via Release of ATP and Activation of P2Y Receptors

PubMed Central

Kawano, Ayumi; Kadomatsu, Remi; Ono, Miyu; Kojima, Shuji; Tsukimoto, Mitsutoshi; Sakamoto, Hikaru

2015-01-01

Extracellular nucleotides, such as ATP, are released from cells in response to various stimuli and act as intercellular signaling molecules through activation of P2 receptors. Exposure to the ultraviolet radiation A (UVA) component of sunlight causes molecular and cellular damage, and in this study, we investigated the involvement of extracellular nucleotides and P2 receptors in the UVA-induced cellular response. Human keratinocyte-derived HaCaT cells were irradiated with a single dose of UVA (2.5 J/cm2), and ATP release and interleukin (IL)-6 production were measured. ATP was released from cells in response to UVA irradiation, and the release was blocked by pretreatment with inhibitors of gap junction hemichannels or P2X7 receptor antagonist. IL-6 production was increased after UVA irradiation, and this increase was inhibited by ecto-nucleotidase or by antagonists of P2Y11 or P2Y13 receptor. These results suggest that UVA-induced IL-6 production is mediated by release of ATP through hemichannels and P2X7 receptor, followed by activation of P2Y11 and P2Y13 receptors. Interestingly, P2Y11 and P2Y13 were associated with the same pattern of IL-6 production, though they trigger different intracellular signaling cascades: Ca2+-dependent and PI3K-dependent, respectively. Thus, IL-6 production in response to UVA-induced ATP release involves at least two distinct pathways, mediated by activation of P2Y11 and P2Y13 receptors. PMID:26030257

ATP release from freshly isolated guinea-pig bladder urothelial cells: a quantification and study of the mechanisms involved.

PubMed

McLatchie, Linda M; Fry, Christopher H

2015-06-01

To quantify the amount of ATP released from freshly isolated bladder urothelial cells, study its control by intracellular and extracellular calcium and identify the pathways responsible for its release. Urothelial cells were isolated from male guinea-pig urinary bladders and stimulated to release ATP by imposition of drag forces by repeated pipetting. ATP was measured using a luciferin-luciferase assay and the effects of modifying internal and external calcium concentration and blockers of potential release pathways studied. Freshly isolated guinea-pig urothelial cells released ATP at a mean (sem) rate of 1.9 (0.1) pmoles/mm(2) cell membrane, corresponding to about 700 pmoles/g of tissue, and about half [49 (6)%, n = 9) of the available cell ATP. This release was reduced to a mean (sem) of 0.46 (0.08) pmoles/mm(2) (160 pmoles/g) with 1.8 mm external calcium, and was increased about two-fold by increasing intracellular calcium. The release from umbrella cells was not significantly different from a mixed intermediate and basal cell population, suggesting that all three groups of cells release a similar amount of ATP per unit area. ATP release was reduced by ≈ 50% by agents that block pannexin and connexin hemichannels. It is suggested that the remainder may involve vesicular release. A significant fraction of cellular ATP is released from isolated urothelial cells by imposing drag forces that cause minimal loss of cell viability. This release involves multiple release pathways, including hemichannels and vesicular release. © 2014 The Authors BJU International © 2014 BJU International.

46 CFR 45.135 - Hull openings at or below freeboard deck.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Hull openings at or below freeboard deck. 45.135 Section 45.135 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Conditions of Assignment § 45.135 Hull openings at or below freeboard deck. Closures for hull...

Measurements of the stress supported by the crush zone in open hole composite laminates loaded in compression

NASA Technical Reports Server (NTRS)

Guynn, E. Gail; Bradley, Walter L.

1989-01-01

Measurements of the stress supported by the crush zone in open hole specimens loaded in compression were carried out on two composite laminates, AS4/PEEK and IM6/HST-7, containing circular holes of three different diameters. Compression tests were conducted in a specially designed high-axial-alignment material test system machine. Results indicated that the local stress supported in the crush zone is much less than the stress required to initiate the crush, providing the reason for the finding of Guynn et al. (1987) that the Dugdale model does not accurately predict the load-damage size relationship of open hole composite specimens loaded in compression.

Crack-closure and crack-growth measurements in surface-flawed titanium alloy Ti6Al-4V

NASA Technical Reports Server (NTRS)

Elber, W.

1975-01-01

The crack-closure and crack-growth characteristics of the titanium alloy Ti-6Al-4V were determined experimentally on surface-flawed plate specimens. Under cyclic loading from zero to tension, cracks deeper than 1 mm opened at approximately 50 percent of the maximum load. Cracks shallower than 1 mm opened at higher loads. The correlation between crack-growth rate and the total stress-intensity range showed a lower threshold behavior. This behavior was attributed to the high crack-opening loads at short cracks because the lower threshold was much less evident in correlations between the crack-growth rates and the effective stress-intensity range.

Connexins and skin disease: insights into the role of beta connexins in skin homeostasis.

PubMed

Martin, Patricia E M; van Steensel, Maurice

2015-06-01

Cell-to-cell communication triggered by connexin channels plays a central role in maintaining epidermal homeostasis. Here, we discuss the role of the beta connexin subgroup, where site-specific mutations in at least 4 of these proteins lead to distinctive non-inflammatory and inflammatory hyperproliferative epidermal disorders. Recent advances in the molecular pathways evoked and correlation with clinical outcome are discussed. The latest data provide increasing evidence that connexins in the epidermis are sensors to environmental stress and that targeting aberrant hemichannel activity holds significant therapeutic potential for inflammatory skin disorders.

Self locking coupling mechanism for engaging and moving a load

DOEpatents

Wood, R.L.; Casamajor, A.B.; Parsons, R.E.

1980-09-12

A coupling mechanism for engaging and lifting a load has a housing with a guide passage for receiving a knob which is secured to the load through a neck of smaller diameter. A hollow ball in the housing has an opening which receives the knob and the ball is then turned to displace the opening from the housing passage and to cause the neck to enter a slot in the ball thereby securing the load to the coupling mechanism as elements of the housing block travel of the neck back into the opening when the ball is turned to the load holding orientation. As engagement of the load and locking of the coupling mechanism are accomplished simultaneously by the same ball motion, operation is simplified and reliability is greatly increased. The ball is preferably turned by a motor through worm gearing and the coupling mechanism may be controlled from a remote location. Among other uses, the coupling mechanism is adaptable to the handling of spent nuclear reactor fuel elements.

The parameters effect on the structural performance of damaged steel box beam using Taguchi method

NASA Astrophysics Data System (ADS)

El-taly, Boshra A.; Abd El Hameed, Mohamed F.

2018-03-01

In the current study, the influence of notch or opening parameters and the positions of the applied load on the structural performance of steel box beams up to failure was investigated using Finite Element analysis program, ANSYS. The Taguchi-based design of experiments technique was used to plan the current study. The plan included 12 box steel beams; three intact beams, and nine damaged beams (with opening) in the beams web. The numerical studies were conducted under varying the spacing between the two concentrated point loads (location of applied loads), the notch (opening) position, and the ratio between depth and width of the notch with a constant notch area. According to Taguchi analysis, factor X (location of the applied loads) was found the highest contributing parameters for the variation of the ultimate load, vertical deformation, shear stresses, and the compressive normal stresses.

Opening Loads Analyses for Various Disk-Gap-Band Parachutes

NASA Technical Reports Server (NTRS)

Cruz, J. R.; Kandis, M.; Witkowski, A.

2003-01-01

Detailed opening loads data is presented for 18 tests of Disk-Gap-Band (DGB) parachutes of varying geometry with nominal diameters ranging from 43.2 to 50.1 ft. All of the test parachutes were deployed from a mortar. Six of these tests were conducted via drop testing with drop test vehicles weighing approximately 3,000 or 8,000 lb. Twelve tests were conducted in the National Full-Scale Aerodynamics Complex 80- by 120-foot wind tunnel at the NASA Ames Research Center. The purpose of these tests was to structurally qualify the parachute for the Mars Exploration Rover mission. A key requirement of all tests was that peak parachute load had to be reached at full inflation to more closely simulate the load profile encountered during operation at Mars. Peak loads measured during the tests were in the range from 12,889 to 30,027 lb. Of the two test methods, the wind tunnel tests yielded more accurate and repeatable data. Application of an apparent mass model to the opening loads data yielded insights into the nature of these loads. Although the apparent mass model could reconstruct specific tests with reasonable accuracy, the use of this model for predictive analyses was not accurate enough to set test conditions for either the drop or wind tunnel tests. A simpler empirical model was found to be suitable for predicting opening loads for the wind tunnel tests to a satisfactory level of accuracy. However, this simple empirical model is not applicable to the drop tests.

Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells

PubMed Central

Figueroa, Vania A.; Retamal, Mauricio A.; Cea, Luis A.; Salas, José D.; Vargas, Aníbal A.; Verdugo, Christian A.; Jara, Oscar; Martínez, Agustín D.; Sáez, Juan C.

2014-01-01

Gap junction channels (GJCs) and hemichannels (HCs) are composed of protein subunits termed connexins (Cxs) and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the adenosine triphosphate release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects. PMID:25237294

ATP Released by Electrical Stimuli Elicits Calcium Transients and Gene Expression in Skeletal Muscle*

PubMed Central

Buvinic, Sonja; Almarza, Gonzalo; Bustamante, Mario; Casas, Mariana; López, Javiera; Riquelme, Manuel; Sáez, Juan Carlos; Huidobro-Toro, Juan Pablo; Jaimovich, Enrique

2009-01-01

ATP released from cells is known to activate plasma membrane P2X (ionotropic) or P2Y (metabotropic) receptors. In skeletal muscle cells, depolarizing stimuli induce both a fast calcium signal associated with contraction and a slow signal that regulates gene expression. Here we show that nucleotides released to the extracellular medium by electrical stimulation are partly involved in the fast component and are largely responsible for the slow signals. In rat skeletal myotubes, a tetanic stimulus (45 Hz, 400 1-ms pulses) rapidly increased extracellular levels of ATP, ADP, and AMP after 15 s to 3 min. Exogenous ATP induced an increase in intracellular free Ca2+ concentration, with an EC50 value of 7.8 ± 3.1 μm. Exogenous ADP, UTP, and UDP also promoted calcium transients. Both fast and slow calcium signals evoked by tetanic stimulation were inhibited by either 100 μm suramin or 2 units/ml apyrase. Apyrase also reduced fast and slow calcium signals evoked by tetanus (45 Hz, 400 0.3-ms pulses) in isolated mouse adult skeletal fibers. A likely candidate for the ATP release pathway is the pannexin-1 hemichannel; its blockers inhibited both calcium transients and ATP release. The dihydropyridine receptor co-precipitated with both the P2Y2 receptor and pannexin-1. As reported previously for electrical stimulation, 500 μm ATP significantly increased mRNA expression for both c-fos and interleukin 6. Our results suggest that nucleotides released during skeletal muscle activity through pannexin-1 hemichannels act through P2X and P2Y receptors to modulate both Ca2+ homeostasis and muscle physiology. PMID:19822518

FasL-triggered death of Jurkat cells requires caspase 8-induced, ATP-dependent cross-talk between Fas and the purinergic receptor P2X(7).

PubMed

Aguirre, Adam; Shoji, Kenji F; Sáez, Juan C; Henríquez, Mauricio; Quest, Andrew F G

2013-02-01

Fas ligation via the ligand FasL activates the caspase-8/caspase-3-dependent extrinsic death pathway. In so-called type II cells, an additional mechanism involving tBid-mediated caspase-9 activation is required to efficiently trigger cell death. Other pathways linking FasL-Fas interaction to activation of the intrinsic cell death pathway remain unknown. However, ATP release and subsequent activation of purinergic P2X(7) receptors (P2X(7)Rs) favors cell death in some cells. Here, we evaluated the possibility that ATP release downstream of caspase-8 via pannexin1 hemichannels (Panx1 HCs) and subsequent activation of P2X(7)Rs participate in FasL-stimulated cell death. Indeed, upon FasL stimulation, ATP was released from Jurkat cells in a time- and caspase-8-dependent manner. Fas and Panx1 HCs colocalized and inhibition of the latter, but not connexin hemichannels, reduced FasL-induced ATP release. Extracellular apyrase, which hydrolyzes ATP, reduced FasL-induced death. Also, oxidized-ATP or Brilliant Blue G, two P2X(7)R blockers, reduced FasL-induced caspase-9 activation and cell death. These results represent the first evidence indicating that the two death receptors, Fas and P2X(7)R connect functionally via caspase-8 and Panx1 HC-mediated ATP release to promote caspase-9/caspase-3-dependent cell death in lymphoid cells. Thus, a hitherto unsuspected route was uncovered connecting the extrinsic to the intrinsic pathway to amplify death signals emanating from the Fas receptor in type II cells. Copyright © 2012 Wiley Periodicals, Inc.

17 CFR 270.6c-10 - Exemption for certain open-end management investment companies to impose deferred sales loads.

Code of Federal Regulations, 2010 CFR

2010-04-01

... management investment companies to impose deferred sales loads. 270.6c-10 Section 270.6c-10 Commodity and... ACT OF 1940 § 270.6c-10 Exemption for certain open-end management investment companies to impose... purposes of this section: (1) Company means a registered open-end management investment company, other than...

Measuring alignment of loading fixture

DOEpatents

Scavone, Donald W.

1989-01-01

An apparatus and method for measuring the alignment of a clevis and pin type loading fixture for compact tension specimens include a pair of substantially identical flat loading ligaments. Each loading ligament has two apertures for the reception of a respective pin of the loading fixture and a thickness less than one-half of a width of the clevis opening. The pair of loading ligaments are mounted in the clevis openings at respective sides thereof. The loading ligaments are then loaded by the pins of the loading fixture and the strain in each loading ligament is measured. By comparing the relative strain of each loading ligament, the alignment of the loading fixture is determined. Preferably, a suitable strain gage device is located at each longitudinal edge of a respective loading ligament equidistant from the two apertures in order to determine the strain thereat and hence the strain of each ligament. The loading ligaments are made substantially identical by jig grinding the loading ligaments as a matched set. Each loading ligament can also be individually calibrated prior to the measurement.

A Generalized Maxwell Model for Creep Behavior of Artery Opening Angle

PubMed Central

Zhang, W.; Guo, X.; Kassab, G. S.

2009-01-01

An artery ring springs open into a sector after a radial cut. The opening angle characterizes the residual strain in the unloaded state, which is fundamental to understanding stress and strain in the vessel wall. A recent study revealed that the opening angle decreases with time if the artery is cut from the loaded state, while it increases if the cut is made from the no-load state due to viscoelasticity. In both cases, the opening angle approaches the same value in 3 hours. This implies that the characteristic relaxation time is about 10,000 sec. Here, the creep function of a generalized Maxwell model (a spring in series with six Voigt bodies) is used to predict the temporal change of opening angle in multiple time scales. It is demonstrated that the theoretical model captures the salient features of the experimental results. The proposed creep function may be extended to study the viscoelastic response of blood vessels under various loading conditions. PMID:19045526

2. General oblique view of north loading dock showing loading ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. General oblique view of north loading dock showing loading docks with doors opening into refrigerated rooms - Fort Hood, World War II Temporary Buildings, Cold Storage Building, Seventeenth Street, Killeen, Bell County, TX

Connexins and Pannexins in Vascular Function and Disease.

PubMed

Molica, Filippo; Figueroa, Xavier F; Kwak, Brenda R; Isakson, Brant E; Gibbins, Jonathan M

2018-06-05

Connexins (Cxs) and pannexins (Panxs) are ubiquitous membrane channel forming proteins that are critically involved in many aspects of vascular physiology and pathology. The permeation of ions and small metabolites through Panx channels, Cx hemichannels and gap junction channels confers a crucial role to these proteins in intercellular communication and in maintaining tissue homeostasis. This review provides an overview of current knowledge with respect to the pathophysiological role of these channels in large arteries, the microcirculation, veins, the lymphatic system and platelet function. The essential nature of these membrane proteins in vascular homeostasis is further emphasized by the pathologies that are linked to mutations and polymorphisms in Cx and Panx genes.

Strain measurements in composite bolted-joint specimens

NASA Technical Reports Server (NTRS)

Hyer, M. W.; Lightfoot, M. C.; Perry, J. C.

1979-01-01

Strain data from a series of bolted joint tests is presented. Double lap, double hole, double lap, single hole, and open hole tensile specimens were tested and the strain gage locations, load strain responses, and load axial displacement responses are presented. The open hole specimens were gaged to determine strain concentration factors. The double lap, double hole specimens were gaged to determine the uniformity of the strain in the joint and the amount of load transferred past the first bolt. The measurements indicated roughly half the load passed the first bolt to be reacted by the second bolt.

Methamphetamine compromises gap junctional communication in astrocytes and neurons

PubMed Central

Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R.; Eugenin, Eliseo A.

2016-01-01

Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood–brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. PMID:26953131

Connexin 26 facilitates gastrointestinal bacterial infection in vitro.

PubMed

Simpson, Charlotte; Kelsell, David P; Marchès, Olivier

2013-01-01

Escherichia coli, including enteropathogenic E. coli (EPEC), represents the most common cause of diarrhoea worldwide and is therefore a serious public health burden. Treatment for gastrointestinal pathogens is hindered by the emergence of multiple antibiotic resistance, leading to the requirement for the development of new therapies. A variety of mechanisms act in combination to mediate gastrointestinal-bacterial-associated diarrhoea development. For example, EPEC infection of enterocytes induces attaching and effacing lesion formation and the disruption of tight junctions. An alternative enteric pathogen, Shigella flexneri, manipulates the expression of Connexin 26 (Cx26), a gap junction protein. S. flexneri can open Cx26 hemichannels allowing the release of ATP, whereas HeLa cells expressing mutant gap-junction-associated Cx26 are less susceptible to cellular invasion by S. flexneri than cells expressing wild-type (WT) Cx26. We have investigated further the link between Cx26 expression and gastrointestinal infection by using EPEC and S. flexneri as in vitro models of infection. In this study, a significant reduction in EPEC adherence was observed in cells expressing mutant Cx26 compared with WT Cx26. Furthermore, a significant reduction in both cellular invasion by S. flexneri and adherence by EPEC was demonstrated in human intestinal cell lines following treatment with Cx26 short interfering RNA. These in vitro results suggest that the loss of functional Cx26 expression provides improved protection against gastrointestinal bacterial pathogens. Thus, Cx26 represents a potential therapeutic target for gastrointestinal bacterial infection.

Functional expression of Ca²⁺ dependent mammalian transmembrane gap junction protein Cx43 in slime mold Dictyostelium discoideum.

PubMed

Kaufmann, Stefan; Weiss, Ingrid M; Eckstein, Volker; Tanaka, Motomu

2012-03-09

In this paper, we expressed murine gap junction protein Cx43 in Dictyostelium discoideum by introducing the specific vector pDXA. In the first step, the successful expression of Cx43 and Cx43-eGFP was verified by (a) Western blot (anti-Cx43, anti-GFP), (b) fluorescence microscopy (eGFP-Cx43 co-expression, Cx43 immunostaining), and (c) flow cytometry analysis (eGFP-Cx43 co-expression). Although the fluorescence signals from cells expressing Cx43-eGFP detected by fluorescence microscopy seem relatively low, analysis by flow cytometry demonstrated that more than 60% of cells expressed Cx43-eGFP. In order to evaluate the function of expressed Cx43 in D. discoideum, we examined the hemi-channel function of Cx43. In this series of experiments, the passive uptake of carboxyfluorescein was monitored using flow cytometric analysis. A significant number of the transfected cells showed a prominent dye uptake in the absence of Ca(2+). The dye uptake by transfected cells in the presence of Ca(2+) was even lower than the non-specific dye uptake by non-transformed Ax3 orf+ cells, confirming that Cx43 expressed in D. discoideum retains its Ca(2+)-dependent, specific gating function. The expression of gap junction proteins expressed in slime molds opens a possibility to the biological significance of intercellular communications in development and maintenance of multicellular organisms. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular pathways of pannexin1-mediated neurotoxicity

PubMed Central

Shestopalov, Valery I.; Slepak, Vladlen Z.

2014-01-01

Pannexin1 (Panx1) forms non-selective membrane channels, structurally similar to gap junction hemichannels, and are permeable to ions, nucleotides, and other small molecules below 900 Da. Panx1 activity has been implicated in paracrine signaling and inflammasome regulation. Recent studies in different animal models showed that overactivation of Panx1 correlates with a selective demise of several types of neurons, including retinal ganglion cells, brain pyramidal, and enteric neurons. The list of Panx1 activators includes extracellular ATP, glutamate, high K+, Zn2+, fibroblast growth factors (FGFs),pro-inflammatory cytokines, and elevation of intracellular Ca2+. Most of these molecules are released following mechanical, ischemic, or inflammatory injury of the CNS, and rapidly activate the Panx1 channel. Prolonged opening of Panx1 channel induced by these “danger signals” triggers a cascade of neurotoxic events capable of killing cells. The most vulnerable cell type are neurons that express high levels of Panx1. Experimental evidence suggests that Panx1 channels mediate at least two distinct neurotoxic processes: increased permeability of the plasma membrane and activation of the inflammasome in neurons and glia. Importantly, both pharmacological and genetic inactivation of Panx1 suppresses both these processes, providing a marked protection in several disease and injury models. These findings indicate that external danger signals generated after diverse types of injuries converge to activate Panx1. In this review we discuss molecular mechanisms associated with Panx1 toxicity and the crosstalk between different pathways. PMID:24575045

Self locking coupling mechanism for engaging and moving a load

DOEpatents

Wood, Richard L.; Casamajor, Alan B.; Parsons, Richard E.

1982-01-01

Coupling mechanism (11) for engaging and lifting a load (12) has a housing (19) with a guide passage (18) for receiving a knob (13) which is secured to the load (12) through a neck (15) of smaller diameter. A hollow ball (23) in the housing (19) has an opening (27) which receives the knob (13) and the ball (23) is then turned to displace the opening (27) from the housing passage (18) and to cause the neck (15) to enter a slot (29) in the ball (23) thereby securing the load (12) to the coupling mechanism (11) as elements (49) of the housing (19) block travel of the neck (15) back into the opening (27) when the ball (23) is turned to the load holding orientation. As engagement of the load (12) and locking of the coupling mechanism are accomplished simultaneously by the same ball (23) motion, operation is simplified and reliability is greatly increased. The ball (23) is preferably turned by a motor (32) through worm gearing (36) and the coupling mechanism (11) may be controlled from a remote location. Among other uses, the coupling mechanism (11) is adaptable to the handling of spent nuclear reactor fuel elements (12).

High Torque-to-Inertia Servo System for Stabilizing Sensor Systems. Candidate Systems Include Missile Guidance, Surveillance, and Tracking

DTIC Science & Technology

1980-04-01

specifications ... 3-10 25. Typical isolation curve ... 3-12 26. Servo amp/motor/load frequency response (inner gimbal) ... 4-3 27. Slave loop ( open loop...slave loop ( open loop) frequency response (inner gimbal) . . . 4-4 30. Slave loop (closed loop) frequency response (inner gimbal) ... 4-5 3 . Slave...loop inner gimbal time response ... 4-5 32. Servo amp/motor/load frequency response (outer gimbal) ... 4-6 33. Slave loop ( open loop) uncompensated

Method of determining the open circuit voltage of a battery in a closed circuit

DOEpatents

Brown, William E.

1980-01-01

The open circuit voltage of a battery which is connected in a closed circuit is determined without breaking the circuit or causing voltage upsets therein. The closed circuit voltage across the battery and the current flowing through it are determined under normal load and then a fractional change is made in the load and the new current and voltage values determined. The open circuit voltage is then calculated, according to known principles, from the two sets of values.

Active load control during rolling maneuvers. [performed in the Langley Transonic Dynamics Tunnel

NASA Technical Reports Server (NTRS)

Woods-Vedeler, Jessica A.; Pototzky, Anthony S.; Hoadley, Sherwood T.

1994-01-01

A rolling maneuver load alleviation (RMLA) system has been demonstrated on the active flexible wing (AFW) wind tunnel model in the Langley Transonic Dynamics Tunnel (TDT). The objective was to develop a systematic approach for designing active control laws to alleviate wing loads during rolling maneuvers. Two RMLA control laws were developed that utilized outboard control-surface pairs (leading and trailing edge) to counteract the loads and that used inboard trailing-edge control-surface pairs to maintain roll performance. Rolling maneuver load tests were performed in the TDT at several dynamic pressures that included two below and one 11 percent above open-loop flutter dynamic pressure. The RMLA system was operated simultaneously with an active flutter suppression system above open-loop flutter dynamic pressure. At all dynamic pressures for which baseline results were obtained, torsion-moment loads were reduced for both RMLA control laws. Results for bending-moment load reductions were mixed; however, design equations developed in this study provided conservative estimates of load reduction in all cases.

Effects of wet mat curing time and earlier loading on long-term durability of bridge decks : compressive strength, maturity and strength durability index (SDI).

DOT National Transportation Integrated Search

2009-01-01

There is increasing pressure from owners, contractors, and the public to open bridge decks sooner to full : traffic loads. As a result, a set of criteria or guidelines is needed to determine when concrete bridge decks can : safely be opened. Today, c...

Biomechanical Modeling Analysis of Loads Configuration for Squat Exercise

NASA Technical Reports Server (NTRS)

Gallo, Christopher A.; Thompson, William K.; Lewandowski, Beth E.; Jagodnik, Kathleen; De Witt, John K.

2017-01-01

INTRODUCTION: Long duration space travel will expose astronauts to extended periods of reduced gravity. Since gravity is not present to assist loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft for travel to the Moon or to Mars is limited and therefore compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Biomechanical data collection and computational modeling aid the device design process by quantifying the joint torques and the musculoskeletal forces that occur during exercises performed on the prototype devices. METHODS The computational models currently under development utilize the OpenSim [1] software platform, consisting of open source code for musculoskeletal modeling, using biomechanical input data from test subjects for estimation of muscle and joint loads. The OpenSim Full Body Model [2] is used for all analyses. The model incorporates simplified wrap surfaces, a new knee model and updated lower body muscle parameters derived from cadaver measurements and magnetic resonance imaging of young adults. The upper body uses torque actuators at the lumbar and extremity joints. The test subjects who volunteer for this study are instrumented with reflective markers for motion capture data collection while performing squat exercising on the Hybrid Ultimate Lifting Kit (HULK) prototype device (ZIN Technologies, Middleburg Heights, OH). Ground reaction force data is collected with force plates under the feet, and device loading is recorded through load cells internal to the HULK. Test variables include the applied device load and the dual cable long bar or single cable T-bar interface between the test subject and the device. Data is also obtained using free weights with the identical loading for a comparison to the resistively loaded exercise device trials. The data drives the OpenSim biomechanical model, which has been scaled to match the anthropometrics of the test subject, to calculate the body loads. RESULTS Lower body kinematics, joint moments, joint forces and muscle forces are obtained from the OpenSim biomechanical analysis of the squat exercises under different loading conditions. Preliminary results from the model for the loading conditions will be presented as will hypotheses developed for follow on work.

Opportunities for Energy Efficiency and Automated Demand Response in Industrial Refrigerated Warehouses in California

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lekov, Alex; Thompson, Lisa; McKane, Aimee

2009-05-11

This report summarizes the Lawrence Berkeley National Laboratory's research to date in characterizing energy efficiency and open automated demand response opportunities for industrial refrigerated warehouses in California. The report describes refrigerated warehouses characteristics, energy use and demand, and control systems. It also discusses energy efficiency and open automated demand response opportunities and provides analysis results from three demand response studies. In addition, several energy efficiency, load management, and demand response case studies are provided for refrigerated warehouses. This study shows that refrigerated warehouses can be excellent candidates for open automated demand response and that facilities which have implemented energy efficiencymore » measures and have centralized control systems are well-suited to shift or shed electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. Control technologies installed for energy efficiency and load management purposes can often be adapted for open automated demand response (OpenADR) at little additional cost. These improved controls may prepare facilities to be more receptive to OpenADR due to both increased confidence in the opportunities for controlling energy cost/use and access to the real-time data.« less

Flow processes in overexpanded chemical rocket nozzles. Part 3: Methods for the aimed flow separation and side load reduction

NASA Technical Reports Server (NTRS)

Schmucker, R. H.

1983-01-01

Methods aimed at reduction of overexpansion and side load resulting from asymmetric flow separation for rocket nozzles with a high opening ratio are described. The methods employ additional measures for nozzles with a fixed opening ratio. The flow separation can be controlled by several types of nozzle inserts, the properties of which are discussed. Side loads and overexpansion can be reduced by adapting the shape of the nozzle and taking other additional measures for controlled separation of the boundary layer, such as trip wires.

Open Screw Placement in a 1.5 mm LCP Over a Fracture Gap Decreases Fatigue Life

PubMed Central

Alwen, Sarah G. J.; Kapatkin, Amy S.; Garcia, Tanya C.; Milgram, Joshua; Stover, Susan M.

2018-01-01

Objective To investigate the influence of plate and screw hole position on the stability of simulated radial fractures stabilized with a 1.5 mm condylar locking compression plate (LCP). Study Design In vitro mechanical testing of paired cadaveric limbs. Sample Population Paired radii (n = 7) stabilized with a 1.5 mm condylar LCP with an open screw hole positioned either proximal to (PG), or over (OG), a simulated small fracture gap. Methods Constructs were cycled in axial compression at a simulated trot load until failure or a maximum of 200,000 cycles. Specimens that sustained 200,000 cycles without failure were then loaded in axial compression in a single cycle to failure. Construct cyclic axial stiffness and gap strain, fatigue life, and residual strength were evaluated and compared between constructs using analysis of variance. Results Of pairs that had a failure during cyclic loading, OG constructs survived fewer cycles (54,700 ± 60,600) than PG (116,800 ± 49,300). OG constructs had significantly lower initial stiffness throughout cyclic loading and higher gap strain range within the first 1,000 cycles than PG constructs. Residual strength variables were not significantly different between constructs, however yield loads occurred at loads only marginally higher than approximated trot loads. Fatigue life decreased with increasing body weight. Conclusion Fracture fixation stability is compromised by an open screw hole directly over a fracture gap compared to the open screw hole being buttressed by bone in the model studied. The 1.5 mm condylar LCP may be insufficient stabilization in dogs with appropriate radial geometry but high body weights. PMID:29876361

Stress-intensity factors and crack-opening displacements for round compact specimens. [fracture toughness of metallic materials

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.

1979-01-01

A two dimensional, boundary collocation stress analysis was used to analyze various round compact specimens. The influence of the round external boundary and of pin-loaded holes on stress intensity factors and crack opening displacements was determined as a function of crack-length-to-specimen-width ratios. A wide-range equation for the stress intensity factors was developed. Equations for crack-surface displacements and load-point displacements were also developed. In addition, stress intensity factors were calculated from compliance methods to demonstrate that load-displacement records must be made at the loading points and not along the crack line for crack-length-to-specimen-width ratios less than about 0.4.

Long-Term Wet and Dry Deposition of Total and Methyl Mercury in the Remote Boreal Ecoregion of Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graydon, Jennifer A; Louis, Vincent; Hintelmann, Holger

2008-11-01

Although a positive relationship between atmospheric loadings of inorganic mercury (Hg(II)) to watersheds and concentrations of methyl mercury (MeHg) in fish has now been established, net wet and dry deposition of Hg(II) and MeHg to watersheds remains challenging to quantify. In this study, concentrations and loadings of total mercury (THg; all forms of Hg in a sample) and MeHg in open area wet deposition, throughfall, and litterfall were quantified at the remote Experimental Lakes Area in the boreal ecoregion, NW Ontario, Canada. Between 1992 and 2006, mean annual THg and MeHg loadings in the open were 36 17 and 0.5more » 0.2 mg ha 1, respectively. Throughfall THg and MeHg loadings were generally 2 4 times and 0.8 2 times higher, respectively, than loadings in the open. Loadings of both THg and MeHg were highest under an old growth spruce/fir canopy and lowest under a deciduous maple canopy, whereas loadings under young jack pine and wetland spruce/pine/alder canopies were intermediate. Litterfall generally represented the largest input of THg (86 105 mg ha 1) and MeHg (0.7 0.8 mg ha 1) to the landscape on an annual basis. Using the direct method of estimating dry deposition (thoughfall + litterfall open loadings), we calculated that annual dry deposition of THg and MeHg under forest canopies ranged from 105 to 201 mg ha 1, whereas dry deposition of MeHg ranged from 0.7 to 1.2 mg ha 1. Photoreduction and emission of wet-deposited Hg(II) from canopy foliage were accounted for, resulting in 3 5% (5 6 mg ha 1) higher annual estimates of dry deposition than via the direct method alone. Net THg and MeHg loadings to this remote landscape were lower than at any other previously studied forested site globally. This study shows that THg and MeHg loading can be extremely variable within a heterogeneous boreal landscape and that processes such as Hg photoreduction and emission from foliage should be considered when estimating dry deposition of Hg.« less

The structure of a ring-opened proliferating cell nuclear antigen-replication factor C complex revealed by fluorescence energy transfer.

PubMed

Zhuang, Zhihao; Yoder, Bonita L; Burgers, Peter M J; Benkovic, Stephen J

2006-02-21

Numerous proteins that function in DNA metabolic pathways are known to interact with the proliferating cell nuclear antigen (PCNA). The important function of PCNA in stimulating various cellular activities requires its topological linkage with DNA. Loading of the circular PCNA onto duplex DNA requires the activity of a clamp-loader [replication factor C (RFC)] complex and the energy derived from ATP hydrolysis. The mechanistic and structural details regarding PCNA loading by the RFC complex are still developing. In particular, the positive identification of a long-hypothesized structure of an open clamp-RFC complex as an intermediate in loading has remained elusive. In this study, we capture an open yeast PCNA clamp in a complex with RFC through fluorescence energy transfer experiments. We also follow the topological transitions of PCNA in the various steps of the clamp-loading pathway through both steady-state and stopped-flow fluorescence studies. We find that ATP effectively drives the clamp-loading process to completion with the formation of the closed PCNA bound to DNA, whereas ATPgammaS cannot. The information derived from this work complements that obtained from previous structural and mechanistic studies and provides a more complete picture of a eukaryotic clamp-loading pathway using yeast as a paradigm.

Experimental analysis on the dynamic wake of an actuator disc undergoing transient loads

NASA Astrophysics Data System (ADS)

Yu, W.; Hong, V. W.; Ferreira, C.; van Kuik, G. A. M.

2017-10-01

The Blade Element Momentum model, which is based on the actuator disc theory, is still the model most used for the design of open rotors. Although derived from steady cases with a fully developed wake, this approach is also applied to unsteady cases, with additional engineering corrections. This work aims to study the impact of an unsteady loading on the wake of an actuator disc. The load and flow of an actuator disc are measured in the Open Jet Facility wind tunnel of Delft University of Technology, for steady and unsteady cases. The velocity and turbulence profiles are characterized in three regions: the inner wake region, the shear layer region and the region outside the wake. For unsteady load cases, the measured velocity field shows a hysteresis effect in relation to the loading, showing differences between the cases when loading is increased and loading is decreased. The flow field also shows a transient response to the step change in loading, with either an overshoot or undershoot of the velocity in relation to the steady-state velocity. In general, a smaller reduced ramp time results in a faster velocity transient, and in turn a larger amplitude of overshoot or undershoot. Time constants analysis shows that the flow reaches the new steady-state slower for load increase than for load decrease; the time constants outside the wake are generally larger than at other radial locations for a given downstream plane; the time constants of measured velocity in the wake show radial dependence.The data are relevant for the validation of numerical models for unsteady actuator discs and wind turbines, and are made available in an open source database (see Appendix).

Effects of transcranial direct current stimulation on hemichannel pannexin-1 and neural plasticity in rat model of cerebral infarction.

PubMed

Jiang, T; Xu, R X; Zhang, A W; Di, W; Xiao, Z J; Miao, J Y; Luo, N; Fang, Y N

2012-12-13

The aim of this study was to investigate the effects of transcranial direct current stimulation (TDCS) on hemichannel pannexin-1 (PX1) in cortical neurons and neural plasticity, and explore the optimal time window of TDCS therapy after stroke. Adult male Sprague-Dawley rats (n=90) were randomly assigned to sham operation, middle cerebral artery occlusion (MCAO), and TDCS groups, and underwent sham operation, unilateral middle cerebral artery (MCA) electrocoagulation, and unilateral MCA electrocoagulation plus TDCS (daily anodal and cathodal 10 Hz, 0.1 mA TDCS for 30 min beginning day 1 after stroke), respectively. Motor function was assessed using the beam walking test (BWT), and density of dendritic spines (DS) and PX1 mRNA expression were compared among groups on days 3, 7, and 14 after stroke. Effects of PX1 blockage on DS in hippocampal neurons after hypoxia-ischemia were observed. TDCS significantly improved motor function on days 7 and 14 after stroke as indicated by reduced BWT scores compared with the MCAO group. The density of DS was decreased after stroke; the TDCS group had increased DS density compared with the MCAO group on days 3, 7, and 14 (all P<0.0001). Cerebral infarction induced increased PX1 mRNA expression on days 3, 7, and 14 (P<0.0001), and the peak PX1 mRNA expression was observed on day 7. TDCS did not decrease the up-regulated PX1 mRNA expression after stroke on day 3, but did reduce the increased post-stroke PX1 mRNA expression on days 7 and 14 (P<0.0001). TDCS increased the DS density after stroke, indicating that it may promote neural plasticity after stroke. TDCS intervention from day 7 to day 14 after stroke demonstrated motor function improvement and can down-regulate the elevated PX1 mRNA expression after stroke. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Gap junction disorders of myelinating cells.

PubMed

Kleopa, Kleopas A; Orthmann-Murphy, Jennifer; Sargiannidou, Irene

2010-01-01

Gap junctions (GJs) are channels that allow the diffusion of ions and small molecules across apposed cell membranes. In peripheral nerves, Schwann cells express the GJ proteins connexin32 (Cx32) and Cx29, which have distinct localizations. Cx32 forms GJs through non-compact myelin areas, whereas Cx29 forms hemichannels in the innermost layers of myelin apposing axonal Shaker-type K+ channels. In the CNS, rodent oligodendrocytes express Cx47, Cx32 and Cx29. Cx47 is expressed by all types of oligodendrocytes both in the white and grey matter and forms GJs on cell bodies and proximal processes, as well as most of the intercellular channels with astrocytes. Cx32 is expressed mostly by white matter oligodendrocytes and is localized in the myelin sheath of large diameter fibers. Cx29, and its human ortholog Cx31.3, appear to be restricted to oligodendrocytes that myelinate small caliber fibers, likely forming hemichannels. The importance of intercellular and intracellular GJs in myelinating cells are demonstrated by human disorders resulting from mutations affecting GJ proteins. The X-linked Charcot Marie Tooth disease (CMT1X) is caused by hundreds of mutations affecting Cx32. Patients with CMT1X present mainly with a progressive peripheral neuropathy, which may be accompanied by CNS myelin dysfunction. Mutations in Cx47 may cause a devastating leukodystrophy called Pelizaeus-Merzbacher-like disease or a milder spastic paraplegia. In addition, CNS demyelination may be caused by defects in genes expressing astrocytic GJ proteins, which are essential for oligodendrocytes. Findings from in vitro and in vivo models of these disorders developed over the last decade indicate that most mutations cause loss of function and an inability of the mutant connexins to form functional GJs. Here we review the clinical, genetic, and neurobiological aspects of GJ disorders affecting the PNS and CNS myelinating cells.

Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.

2011-08-05

Highlights: {yields} Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. {yields} First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. {yields} Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. {yields} Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. {yields} Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides themore » reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b{sub 5} and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.« less

The EST Model for Predicting Progressive Damage and Failure of Open Hole Bending Specimens

NASA Technical Reports Server (NTRS)

Joseph, Ashith P. K.; Waas, Anthony M.; Pineda, Evan J.

2016-01-01

Progressive damage and failure in open hole composite laminate coupons subjected to flexural loading is modeled using Enhanced Schapery Theory (EST). Previous studies have demonstrated that EST can accurately predict the strength of open hole coupons under remote tensile and compressive loading states. This homogenized modeling approach uses single composite shell elements to represent the entire laminate in the thickness direction and significantly reduces computational cost. Therefore, when delaminations are not of concern or are active in the post-peak regime, the version of EST presented here is a good engineering tool for predicting deformation response. Standard coupon level tests provides all the input data needed for the model and they are interpreted in conjunction with finite element (FE) based simulations. Open hole bending test results of three different IM7/8552 carbon fiber composite layups agree well with EST predictions. The model is able to accurately capture the curvature change and deformation localization in the specimen at and during the post catastrophic load drop event.

Theoretical Modeling of the Plasma Erosion Opening Switch for Inductive Storage Applications.

DTIC Science & Technology

1983-10-27

instantaneous and depends on the switch and load characteristics. In general T is finite and T >T >0. Thus energy will be lost to switch heatings s op - as...Top, then the switch opening time is the dominant factor and T T Clearly T must be small compared with the decay time of the load S op 5 current, T_

Biomechanical behavior of bone scaffolds made of additive manufactured tricalciumphosphate and titanium alloy under different loading conditions.

PubMed

Wieding, Jan; Fritsche, Andreas; Heinl, Peter; Körner, Carolin; Cornelsen, Matthias; Seitz, Hermann; Mittelmeier, Wolfram; Bader, Rainer

2013-12-16

The repair of large segmental bone defects caused by fracture, tumor or infection remains challenging in orthopedic surgery. The capability of two different bone scaffold materials, sintered tricalciumphosphate and a titanium alloy (Ti6Al4V), were determined by mechanical and biomechanical testing. All scaffolds were fabricated by means of additive manufacturing techniques with identical design and controlled pore geometry. Small-sized sintered TCP scaffolds (10 mm diameter, 21 mm length) were fabricated as dense and open-porous samples and tested in an axial loading procedure. Material properties for titanium alloy were determined by using both tensile (dense) and compressive test samples (open-porous). Furthermore, large-sized open-porous TCP and titanium alloy scaffolds (30 mm in height and diameter, 700 µm pore size) were tested in a biomechanical setup simulating a large segmental bone defect using a composite femur stabilized with an osteosynthesis plate. Static physiologic loads (1.9 kN) were applied within these tests. Ultimate compressive strength of the TCP samples was 11.2 ± 0.7 MPa and 2.2 ± 0.3 MPa, respectively, for the dense and the open-porous samples. Tensile strength and ultimate compressive strength was 909.8 ± 4.9 MPa and 183.3 ± 3.7 MPa, respectively, for the dense and the open-porous titanium alloy samples. Furthermore, the biomechanical results showed good mechanical stability for the titanium alloy scaffolds. TCP scaffolds failed at 30% of the maximum load. Based on recent data, the 3D printed TCP scaffolds tested cannot currently be recommended for high load-bearing situations. Scaffolds made of titanium could be optimized by adapting the biomechanical requirements.

Mechanism of opening a sliding clamp

PubMed Central

Douma, Lauren G.; Yu, Kevin K.; England, Jennifer K.

2017-01-01

Abstract Clamp loaders load ring-shaped sliding clamps onto DNA where the clamps serve as processivity factors for DNA polymerases. In the first stage of clamp loading, clamp loaders bind and stabilize clamps in an open conformation, and in the second stage, clamp loaders place the open clamps around DNA so that the clamps encircle DNA. Here, the mechanism of the initial clamp opening stage is investigated. Mutations were introduced into the Escherichia coli β-sliding clamp that destabilize the dimer interface to determine whether the formation of an open clamp loader–clamp complex is dependent on spontaneous clamp opening events. In other work, we showed that mutation of a positively charged Arg residue at the β-dimer interface and high NaCl concentrations destabilize the clamp, but neither facilitates the formation of an open clamp loader–clamp complex in experiments presented here. Clamp opening reactions could be fit to a minimal three-step ‘bind-open-lock’ model in which the clamp loader binds a closed clamp, the clamp opens, and subsequent conformational rearrangements ‘lock’ the clamp loader–clamp complex in a stable open conformation. Our results support a model in which the E. coli clamp loader actively opens the β-sliding clamp. PMID:28973453

Factors affecting the open-circuit voltage and electrode kinetics of some iron/titanium redox flow cells

NASA Technical Reports Server (NTRS)

Reid, M. A.; Gahn, R. F.

1977-01-01

Performance of the iron-titanium redox flow cell was studied as a function of acid concentration. Anion permeable membranes separated the compartments. Electrodes were graphite cloth. Current densities ranged up to 25 mA/square centimeter. Open-circuit and load voltages decreased as the acidity was increased on the iron side as predicted. On the titanium side, open-circuit voltages decreased as the acidity was increased in agreement with theory, but load voltages increased due to decreased polarization with increasing acidity. High acidity on the titanium side coupled with low acidity on the iron side gives the best load voltage, but such cells show voltage losses as they are repeatedly cycled. Analyses show that the bulk of the voltage losses are due to diffusion of acid through the membrane.

Finite element modelling of reinforced large-opening on the web of steel beam considering axial forces

NASA Astrophysics Data System (ADS)

Sukrawa, Made

2017-11-01

Experimental and analytical researches on the effect of web opening in steel beams have been repeatedly reported in literature because of the advantages gain from the many function of the opening. Most of the research on this area, however, did not consider deformation and stress in the beam due to axial force. In seismic design of steel structure, the axial force in the beam could be significantly high and therefore worth considering. In this study a beam extracted from a braced frame structure was analyzed using finite element models to investigate the effect of combined bending and axial forces on the deformation and stresses in the vicinity of the opening. Large size of square, rectangular, and circular openings of the same depth were reinforced and placed in pair, symmetrical to the concentrated load at mid span of the beam. Four types of reinforcement were used, all around (AA), short horizontal (SH), long horizontal (LH), and doubler plate (DP). The effect of axial load was also investigated using rigid frame model loaded vertically and laterally. Validation of the modelling technique was done prior to the parametric study. It was revealed that the axial force significantly contributes to the stress concentration near the hole. Stiffener of circular shape was effective to improve the stress distribution around the circular opening. For square and rectangular openings, however, the horizontal stiffener, extended beyond the edge of opening, performed better than the other type of stiffeners.

Periadventitial Application of Rapamycin-Loaded Nanoparticles Produces Sustained Inhibition of Vascular Restenosis

PubMed Central

Guo, Lian-Wang; Si, Yi; Zhu, Men; Pilla, Srikanth; Liu, Bo; Gong, Shaoqin; Kent, K. Craig

2014-01-01

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions. PMID:24586612

Nutrient loading and consumers: Agents of change in open-coast macrophyte assemblages

PubMed Central

Nielsen, Karina J.

2003-01-01

Human activities are significantly altering nutrient regimes and the abundance of consumers in coastal ecosystems. A field experiment in an open-coast, upwelling ecosystem showed that small increases in nutrients increased the biomass and evenness of tide pool macrophytes where consumer abundance and nutrient loading rates were low. Consumers, when abundant, had negative effects on the diversity and biomass of macrophytes. Nutrient loading increases and consumers are less abundant and efficient as wave exposure increases along open coastlines. Experimentally reversing the natural state of nutrient supply and consumer pressure at a wave-protected site to match wave-exposed sites caused the structure of the macrophyte assemblage to converge on that found naturally in wave-exposed pools. The increases in evenness and abundance were driven by increases in structurally complex functional groups. In contrast, increased nutrient loading in semienclosed marine or estuarine ecosystems is typically associated with declines in macrophyte diversity because of increases in structurally simple and opportunistic functional groups. If nutrient concentration of upwelled waters changes with climatic warming or increasing frequency of El Niños, as predicted by some climate models, these results suggest that macrophyte abundance and evenness along wave-swept open-coasts will also change. Macrophytes represent a significant fraction of continental shelf production and provide important habitat for many marine species. The combined effects of shifting nutrient regimes and overexploitation of consumers may have unexpected consequences for the structure and functioning of open-coast communities. PMID:12796509

Nutrient loading and consumers: agents of change in open-coast macrophyte assemblages.

PubMed

Nielsen, Karina J

2003-06-24

Human activities are significantly altering nutrient regimes and the abundance of consumers in coastal ecosystems. A field experiment in an open-coast, upwelling ecosystem showed that small increases in nutrients increased the biomass and evenness of tide pool macrophytes where consumer abundance and nutrient loading rates were low. Consumers, when abundant, had negative effects on the diversity and biomass of macrophytes. Nutrient loading increases and consumers are less abundant and efficient as wave exposure increases along open coastlines. Experimentally reversing the natural state of nutrient supply and consumer pressure at a wave-protected site to match wave-exposed sites caused the structure of the macrophyte assemblage to converge on that found naturally in wave-exposed pools. The increases in evenness and abundance were driven by increases in structurally complex functional groups. In contrast, increased nutrient loading in semienclosed marine or estuarine ecosystems is typically associated with declines in macrophyte diversity because of increases in structurally simple and opportunistic functional groups. If nutrient concentration of upwelled waters changes with climatic warming or increasing frequency of El Niños, as predicted by some climate models, these results suggest that macrophyte abundance and evenness along wave-swept open-coasts will also change. Macrophytes represent a significant fraction of continental shelf production and provide important habitat for many marine species. The combined effects of shifting nutrient regimes and overexploitation of consumers may have unexpected consequences for the structure and functioning of open-coast communities.

A novel open-tray impression technique for fabrication of a provisional prosthesis on immediate load implants in a completely edentulous arch.

PubMed

Kaneko, Takahiro; Yamagishi, Kiyoshi; Horie, Norio; Shimoyama, Tetsuo

2013-01-01

To evaluate the clinical outcome of a novel open-tray impression technique for fabrication of a provisional prosthesis supported by immediately loaded implants in a completely edentulous arch. An open-tray impression technique was evaluated in this retrospective study that included patients treated between March 2006 and October 2009. Preoperatively, a diagnostic prosthesis was delivered, and a novel open tray was fabricated based on this prosthesis. After implant placement, the impression and interocclusal record were taken simultaneously using the novel open tray. Laboratory-fabricated, screw-retained, all-acrylic resin provisional restorations were delivered on the same day of surgery. The prosthesis was assessed from the day of surgery until replacement with a definitive prosthesis. The study included 21 patients (mean age, 64.5 years) and a total of 125 implants. Of these, 104 implants were immediately loaded. In all patients, well-fitting provisional restorations supported by a minimum of four implants were delivered. Fracture of the first molar cusp was observed in one case after 30 days. However, there was no extensive fracture in the framework or functional disorder of the prosthesis. No implant failed during the follow-up after implant surgery. This protocol enabled fabrication of a well-fitting acrylic resin provisional prosthesis supported by immediately loaded implants because the impression was taken while in centric occlusion and an occlusion identical to the diagnostic prosthesis could be reconstructed.

Temperature-sensitive gating of hCx26: high-resolution Raman spectroscopy sheds light on conformational changes

PubMed Central

Kniggendorf, Ann-Kathrin; Meinhardt-Wollweber, Merve; Yuan, Xiaogang; Roth, Bernhard; Seifert, Astrid; Fertig, Niels; Zeilinger, Carsten

2014-01-01

The temperature-sensitive gating of human Connexin 26 (hCx26) was analyzed with confocal Raman microscopy. High-resolution Raman spectra covering the spectral range between 400 and 1500 rel. cm−1 with a spectral resolution of 1 cm−1 were fully annotated, revealing notable differences between the spectrum recorded from solubilized hCx26 in Ca2+-buffered POPC at 10°C and any other set of protein conditions (temperature, Ca2+ presence, POPC presence). Spectral components originating from specific amino acids show that the TM1/EL1 parahelix and probably the TM4 trans-membrane helix and the plug domain are involved in the gating process responsible for fully closing the hemichannel. PMID:25071948

Temperature-sensitive gating of hCx26: high-resolution Raman spectroscopy sheds light on conformational changes.

PubMed

Kniggendorf, Ann-Kathrin; Meinhardt-Wollweber, Merve; Yuan, Xiaogang; Roth, Bernhard; Seifert, Astrid; Fertig, Niels; Zeilinger, Carsten

2014-07-01

The temperature-sensitive gating of human Connexin 26 (hCx26) was analyzed with confocal Raman microscopy. High-resolution Raman spectra covering the spectral range between 400 and 1500 rel. cm(-1) with a spectral resolution of 1 cm(-1) were fully annotated, revealing notable differences between the spectrum recorded from solubilized hCx26 in Ca(2+)-buffered POPC at 10°C and any other set of protein conditions (temperature, Ca(2+) presence, POPC presence). Spectral components originating from specific amino acids show that the TM1/EL1 parahelix and probably the TM4 trans-membrane helix and the plug domain are involved in the gating process responsible for fully closing the hemichannel.

POSTOP: Postbuckled open-stiffener optimum panels, user's manual

NASA Technical Reports Server (NTRS)

Biggers, S. B.; Dickson, J. N.

1984-01-01

The computer program POSTOP developed to serve as an aid in the analysis and sizing of stiffened composite panels that may be loaded in the postbuckling regime, is intended for the preliminary design of metal or composite panels with open-section stiffeners, subjected to multiple combined biaxial compression (or tension), shear and normal pressure load cases. Longitudinal compression, however, is assumed to be the dominant loading. Temperature, initial bow eccentricity and load eccentricity effects are included. The panel geometry is assumed to be repetitive over several bays in the longitudinal (stiffener) direction as well as in the transverse direction. Analytical routines are included to compute panel stiffnesses, strains, local and panel buckling loads, and skin/stiffener interface stresses. The resulting program is applicable to stiffened panels as commonly used in fuselage, wing, or empennage structures. The capabilities and limitations of the code are described. Instructions required to use the program and several example problems are included.

The role of a conserved proline residue in mediating conformational changes associated with voltage gating of Cx32 gap junctions.

PubMed Central

Ri, Y; Ballesteros, J A; Abrams, C K; Oh, S; Verselis, V K; Weinstein, H; Bargiello, T A

1999-01-01

We have explored the role of a proline residue located at position 87 in the second transmembrane segment (TM2) of gap junctions in the mechanism of voltage-dependent gating of connexin32 (Cx32). Substitution of this proline (denoted Cx32P87) with residues G, A, or V affects channel function in a progressive manner consistent with the expectation that a proline kink (PK) motif exists in the second transmembrane segment (TM2) of this connexin. Mutations of the preceding threonine residue T86 to S, A, C, V, N, or L shift the conductance-voltage relation of wild-type Cx32, such that the mutated channels close at smaller transjunctional voltages. The observed shift in voltage dependence is consistent with a reduction in the open probability of the mutant hemichannels at a transjunctional voltage (Vj) of 0 mV. In both cases in which kinetics were examined, the time constants for reaching steady state were faster for T86N and T86A than for wild type at comparable voltages, suggesting that the T86 mutations cause the energetic destabilization of the open state relative to the other states of the channel protein. The structural underpinnings of the observed effects were explored with Monte Carlo simulations. The conformational space of TM2 helices was found to differ for the T86A, V, N, and L mutants, which produce a less bent helix ( approximately 20 degrees bend angle) compared to the wild type, which has a approximately 37 degrees bend angle. The greater bend angle of the wild-type helix reflects the propensity of the T86 residue to hydrogen bond with the backbone carbonyl of amino acid residue I82. The relative differences in propensity for hydrogen bonding of the mutants relative to the wild-type threonine residue in the constructs we studied (T86A, V, N, L, S, and C) correlate with the shift in the conductance-voltage relation observed for T86 mutations. The data are consistent with a structural model in which the open conformation of the Cx32 channel corresponds to a more bent TM2 helix, and the closed conformation corresponds to a less bent helix. We propose that the modulation of the hydrogen-bonding potential of the T86 residue alters the bend angle of the PK motif and mediates conformational changes between open and closed channel states. PMID:10354417

Open Architecture Data System for NASA Langley Combined Loads Test System

NASA Technical Reports Server (NTRS)

Lightfoot, Michael C.; Ambur, Damodar R.

1998-01-01

The Combined Loads Test System (COLTS) is a new structures test complex that is being developed at NASA Langley Research Center (LaRC) to test large curved panels and cylindrical shell structures. These structural components are representative of aircraft fuselage sections of subsonic and supersonic transport aircraft and cryogenic tank structures of reusable launch vehicles. Test structures are subjected to combined loading conditions that simulate realistic flight load conditions. The facility consists of two pressure-box test machines and one combined loads test machine. Each test machine possesses a unique set of requirements or research data acquisition and real-time data display. Given the complex nature of the mechanical and thermal loads to be applied to the various research test articles, each data system has been designed with connectivity attributes that support both data acquisition and data management functions. This paper addresses the research driven data acquisition requirements for each test machine and demonstrates how an open architecture data system design not only meets those needs but provides robust data sharing between data systems including the various control systems which apply spectra of mechanical and thermal loading profiles.

Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin

PubMed Central

Fontes, Joseph D.; Ramsey, Jon; Polk, Jeremy M; Koop, Andre; Denisova, Janna V.; Belousov, Andrei B.

2015-01-01

Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed. PMID:26017008

Reversing-counterpulse repetitive-pulse inductive storage circuit

DOEpatents

Honig, Emanuel M.

1987-01-01

A high-power reversing-counterpulse repetitive-pulse inductive storage and transfer circuit includes an opening switch, a main energy storage coil, a counterpulse capacitor and a small inductor. After counterpulsing the opening switch off, the counterpulse capacitor is recharged by the main energy storage coil before the load pulse is initiated. This gives the counterpulse capacitor sufficient energy for the next counterpulse operation, although the polarity of the capacitor's voltage must be reversed before that can occur. By using a current-zero switch as the counterpulse start switch, the capacitor is disconnected from the circuit (with a full charge) when the load pulse is initiated, preventing the capacitor from depleting its energy store by discharging through the load. After the load pulse is terminated by reclosing the main opening switch, the polarity of the counterpulse capacitor voltage is reversed by discharging the capacitor through a small inductor and interrupting the discharge current oscillation at zero current and peak reversed voltage. The circuit enables high-power, high-repetition-rate operation with reusable switches and features total control (pulse-to-pulse) over output pulse initiation, duration, repetition rate, and, to some extent, risetime.

Reversing-counterpulse repetitive-pulse inductive storage circuit

DOEpatents

Honig, E.M.

1984-06-05

A high power reversing-counterpulse repetitive-pulse inductive storage and transfer circuit includes an opening switch, a main energy storage coil, a counterpulse capacitor and a small inductor. After counterpulsing the opening switch off, the counterpulse capacitor is recharged by the main energy storage coil before the load pulse is initiated. This gives the counterpulse capacitor sufficient energy for the next counterpulse operation, although the polarity of the capacitor's voltage must be reversed before that can occur. By using a current-zero switch as the counterpulse start switch, the capacitor is disconnected from the circuit (with a full charge) when the load pulse is initiated, preventing the capacitor from depleting its energy store by discharging through the load. After the load pulse is terminated by reclosing the main opening switch, the polarity of the counterpulse capacitor voltage is reversed by discharging the capacitor through a small inductor and interrupting the discharge current oscillation at zero current and peak reversed voltage. The circuit enables high-power, high-repetition-rate operation with reusable switches and features total control (pulse-to-pulse) over output pulse initiation, duration, repetition rate, and, to some extent, risetime.

Closure of mitochondrial potassium channels favors opening of the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria.

PubMed

Korotkov, Sergey M; Brailovskaya, Irina V; Shumakov, Anton R; Emelyanova, Larisa V

2015-06-01

It is known that a closure of ATP sensitive (mitoKATP) or BK-type Ca(2+) activated (mitoKCa) potassium channels triggers opening of the mitochondrial permeability transition pore (MPTP) in cells and isolated mitochondria. We found earlier that the Tl(+)-induced MPTP opening in Ca(2+)-loaded rat liver mitochondria was accompanied by a decrease of 2,4-dinitrophenol-uncoupled respiration and increase of mitochondrial swelling and ΔΨmito dissipation in the medium containing TlNO3 and KNO3. On the other hand, our study showed that the mitoKATP inhibitor, 5-hydroxydecanoate favored the Tl(+)-induced MPTP opening in the inner membrane of Ca(2+)-loaded rat heart mitochondria (Korotkov et al. 2013). Here we showed that 5-hydroxydecanoate increased the Tl(+)-induced MPTP opening in the membrane of rat liver mitochondria regardless of the presence of mitoKATP modulators (diazoxide and pinacidil). This manifested in more pronounced decrease in the uncoupled respiration and acceleration of both the swelling and the ΔΨmito dissipation in isolated rat liver mitochondria, incubated in the medium containing TlNO3, KNO3, and Ca(2+). A slight delay in Ca(2+)-induced swelling of the mitochondria exposed to diazoxide could be result of an inhibition of succinate oxidation by the mitoKATP modulator. Mitochondrial calcium retention capacity (CRC) was markedly decreased in the presence of the mitoKATP inhibitor (5-hydroxydecanoate) or the mitoKCa inhibitor (paxilline). We suggest that the closure of mitoKATP or mitoKCa in calcium loaded mitochondria favors opening of the Tl(+)-induced MPTP in the inner mitochondrial membrane.

On the variation in crack-opening stresses at different locations in a three-dimensional body

NASA Technical Reports Server (NTRS)

Chermahini, R. G.; Blom, Anders F.

1990-01-01

Crack propagation and closure behavior of thin, and thick middle crack tension specimens under constant amplitude loading were investigated using a three dimensional elastic plastic finite element analysis of fatigue crack propagation and closure. In the thin specimens the crack front closed first on the exterior (free) surface and closed last in the interior during the unloading portion of cyclic loading; a load reduced displacement technique was used to determine crack opening stresses at specified locations in the plate from the displacements calculated after the seven cycle. All the locations were on the plate external surface and were located near the crack tip, behind the crack tip, at the centerline of the crack. With this technique, the opening stresses at the specified points were found to be 0.52, 0.42, and 0.39 times the maximum applied stress.

Orthotropic Laminated Open-cell Frameworks Retaining Strong Auxeticity under Large Uniaxial Loading

NASA Astrophysics Data System (ADS)

Tanaka, Hiro; Suga, Kaito; Iwata, Naoki; Shibutani, Yoji

2017-01-01

Anisotropic materials form inside living tissue and are widely applied in engineered structures, where sophisticated structural and functional design principles are essential to employing these materials. This paper presents a candidate laminated open-cell framework, which is an anisotropic material that shows remarkable mechanical performance. Using additive manufacturing, artificial frameworks are fabricated by lamination of in-plane orthotropic microstructures made of elbowed beam and column members; this fabricated structure features orthogonal anisotropy in three-dimensional space. Uniaxial loading tests reveal strong auxeticity (high negative Poisson’s ratios) in the out-of-plane direction, which is retained reproducibly up to the nonlinear elastic region, and is equal under tensile and compressive loading. Finite element simulations support the observed auxetic behaviors for a unit cell in the periodic framework, which preserve the theoretical elastic properties of an orthogonal solid. These findings open the possibility of conceptual materials design based on geometry.

Aerodynamic effects by cooling flows within engine room of a car model

NASA Astrophysics Data System (ADS)

Sawaguchi, T.; Takakura, Y.

2017-10-01

The purpose of this research is to clarify the change of characteristics of aerodynamic drag and lift of a car by the engine loading system (engine arrangement) and the air inlet system (opening area and position) with and without a radiator in wind-tunnel experiments. A simplified car model with 1/5 scale is generated with reproduction of the engine room covered with the transparent acryl externals for visualization. In the wind-tunnel experiments, the moving-belt ground board is adopted to include ground effects with force measurements by use of load cells. The flows are visualized by the smoke method. As results, with enlargement of the opening area, the drag increased overall although depending largely on the engine loading system and the inlet opening position, the front lift increased and the rear left decreased; the effect of the radiator was to relieve the change of the drag and lift.

Plasma opening switch

DOEpatents

Savage, Mark E.; Mendel, Jr., Clifford W.

2001-01-01

A command triggered plasma opening switch assembly using an amplification stage. The assembly surrounds a coaxial transmission line and has a main plasma opening switch (POS) close to the load and a trigger POS upstream from the main POS. The trigger POS establishes two different current pathways through the assembly depended on whether it has received a trigger current pulse. The initial pathway has both POS's with plasma between their anodes and cathodes to form a short across the transmission line and isolating the load. The final current pathway is formed when the trigger POS receives a trigger current pulse which energizes its fast coil to push the conductive plasma out from between its anode and cathode, allowing the main transmission line current to pass to the fast coil of the main POS, thus pushing its plasma out the way so as to establish a direct current pathway to the load.

46 CFR 122.330 - Hatches and other openings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Hatches and other openings. 122.330 Section 122.330... Miscellaneous Operating Requirements § 122.330 Hatches and other openings. (a) Except when operating on lakes, bays, and sounds, or river routes in calm weather, all hatches and openings in the hull, except loading...

46 CFR 122.330 - Hatches and other openings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Hatches and other openings. 122.330 Section 122.330... Miscellaneous Operating Requirements § 122.330 Hatches and other openings. (a) Except when operating on lakes, bays, and sounds, or river routes in calm weather, all hatches and openings in the hull, except loading...

46 CFR 122.330 - Hatches and other openings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Hatches and other openings. 122.330 Section 122.330... Miscellaneous Operating Requirements § 122.330 Hatches and other openings. (a) Except when operating on lakes, bays, and sounds, or river routes in calm weather, all hatches and openings in the hull, except loading...

46 CFR 122.330 - Hatches and other openings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Hatches and other openings. 122.330 Section 122.330... Miscellaneous Operating Requirements § 122.330 Hatches and other openings. (a) Except when operating on lakes, bays, and sounds, or river routes in calm weather, all hatches and openings in the hull, except loading...

46 CFR 122.330 - Hatches and other openings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Hatches and other openings. 122.330 Section 122.330... Miscellaneous Operating Requirements § 122.330 Hatches and other openings. (a) Except when operating on lakes, bays, and sounds, or river routes in calm weather, all hatches and openings in the hull, except loading...

The effect of an overload on the rate of fatigue crack propagation under plane stress conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bao, H.; McEvily, A.J.

1995-07-01

It has been shown that the retardation in the rate of fatigue crack growth following an overload is largely the result of surface-related, plane-stress deformation. In the present article, in order to isolate the plane-stress behavior, the effect of an overload on the subsequent rate of fatigue crack growth of 0.3-mm-thick specimens of 9Cr-1Mo steel has been investigated and compared to results obtained using 6.35-mm-thick specimens. It was found that for the 0.3-mm thickness, as with thicker specimens, two opening load levels were associated with the overload process. The upper opening load is associated with plane-stress deformation in the overloadmore » plastic zone, and this opening process is more clearly observed with thin as compared to thicker specimens. Based upon the determined level of the upper opening load, a semiempirical analysis is developed for calculating the number of delay cycles due to an overload as a function of thickness.« less

An enhanced SOCP-based method for feeder load balancing using the multi-terminal soft open point in active distribution networks

DOE PAGES

Ji, Haoran; Wang, Chengshan; Li, Peng; ...

2017-09-20

The integration of distributed generators (DGs) exacerbates the feeder power flow fluctuation and load unbalanced condition in active distribution networks (ADNs). The unbalanced feeder load causes inefficient use of network assets and network congestion during system operation. The flexible interconnection based on the multi-terminal soft open point (SOP) significantly benefits the operation of ADNs. The multi-terminal SOP, which is a controllable power electronic device installed to replace the normally open point, provides accurate active and reactive power flow control to enable the flexible connection of feeders. An enhanced SOCP-based method for feeder load balancing using the multi-terminal SOP is proposedmore » in this paper. Furthermore, by regulating the operation of the multi-terminal SOP, the proposed method can mitigate the unbalanced condition of feeder load and simultaneously reduce the power losses of ADNs. Then, the original non-convex model is converted into a second-order cone programming (SOCP) model using convex relaxation. In order to tighten the SOCP relaxation and improve the computation efficiency, an enhanced SOCP-based approach is developed to solve the proposed model. Finally, case studies are performed on the modified IEEE 33-node system to verify the effectiveness and efficiency of the proposed method.« less

Gasket and snap ring installation tool

DOEpatents

Southerland, Jr., James M.; Barringer, Jr., Curtis N.

1994-01-01

A tool for installing a gasket and a snap ring including a shaft, a first plate attached to the forward end of the shaft, a second plate slidably carried by the shaft, a spring disposed about the shaft between the first and second plates, and a sleeve that is free to slide over the shaft and engage the second plate. The first plate has a loading surface with a loading groove for receiving a snap ring and a shoulder for holding a gasket. A plurality of openings are formed through the first plate, communicating with the loading groove and approximately equally spaced about the groove. A plurality of rods are attached to the second plate, each rod slidable in one of the openings. In use, the loaded tool is inserted into a hollow pipe or pipe fitting having an internal flange and an internal seating groove, such that the gasket is positioned against the flange and the ring is in the approximate plane of the seating groove. The sleeve is pushed against the second plate, sliding the second plate towards the first plate, compressing the spring and sliding the rods forwards in the openings. The rods engage the snap ring and urge the ring from the loading groove into the seating groove.

Opportunities for Open Automated Demand Response in Wastewater Treatment Facilities in California - Phase II Report. San Luis Rey Wastewater Treatment Plant Case Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Lisa; Lekov, Alex; McKane, Aimee

2010-08-20

This case study enhances the understanding of open automated demand response opportunities in municipal wastewater treatment facilities. The report summarizes the findings of a 100 day submetering project at the San Luis Rey Wastewater Treatment Plant, a municipal wastewater treatment facility in Oceanside, California. The report reveals that key energy-intensive equipment such as pumps and centrifuges can be targeted for large load reductions. Demand response tests on the effluent pumps resulted a 300 kW load reduction and tests on centrifuges resulted in a 40 kW load reduction. Although tests on the facility?s blowers resulted in peak period load reductions ofmore » 78 kW sharp, short-lived increases in the turbidity of the wastewater effluent were experienced within 24 hours of the test. The results of these tests, which were conducted on blowers without variable speed drive capability, would not be acceptable and warrant further study. This study finds that wastewater treatment facilities have significant open automated demand response potential. However, limiting factors to implementing demand response are the reaction of effluent turbidity to reduced aeration load, along with the cogeneration capabilities of municipal facilities, including existing power purchase agreements and utility receptiveness to purchasing electricity from cogeneration facilities.« less

An enhanced SOCP-based method for feeder load balancing using the multi-terminal soft open point in active distribution networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji, Haoran; Wang, Chengshan; Li, Peng

The integration of distributed generators (DGs) exacerbates the feeder power flow fluctuation and load unbalanced condition in active distribution networks (ADNs). The unbalanced feeder load causes inefficient use of network assets and network congestion during system operation. The flexible interconnection based on the multi-terminal soft open point (SOP) significantly benefits the operation of ADNs. The multi-terminal SOP, which is a controllable power electronic device installed to replace the normally open point, provides accurate active and reactive power flow control to enable the flexible connection of feeders. An enhanced SOCP-based method for feeder load balancing using the multi-terminal SOP is proposedmore » in this paper. Furthermore, by regulating the operation of the multi-terminal SOP, the proposed method can mitigate the unbalanced condition of feeder load and simultaneously reduce the power losses of ADNs. Then, the original non-convex model is converted into a second-order cone programming (SOCP) model using convex relaxation. In order to tighten the SOCP relaxation and improve the computation efficiency, an enhanced SOCP-based approach is developed to solve the proposed model. Finally, case studies are performed on the modified IEEE 33-node system to verify the effectiveness and efficiency of the proposed method.« less

Understanding and Exploiting the Effects of Loading on Ultrasonic Sensing Systems for Structural Health Monitoring

DTIC Science & Technology

2012-02-01

method to image fatigue cracks without requiring damage-free baseline measurements. Load-differential imaging maps changes in ultrasonic signals...caused by a small increase in applied load to an image, which enables detecting and locating fatigue cracks that open under load and thus distinguishing...them from other load-dependent effects. This method was successfully demonstrated in the laboratory during fatigue tests on a variety of aluminum

Diminishing detonator effectiveness through electromagnetic effects

DOEpatents

Schill, Jr, Robert A.

2016-09-20

An inductively coupled transmission line with distributed electromotive force source and an alternative coupling model based on empirical data and theory were developed to initiate bridge wire melt for a detonator with an open and a short circuit detonator load. In the latter technique, the model was developed to exploit incomplete knowledge of the open circuited detonator using tendencies common to all of the open circuit loads examined. Military, commercial, and improvised detonators were examined and modeled. Nichrome, copper, platinum, and tungsten are the detonator specific bridge wire materials studied. The improvised detonators were made typically made with tungsten wire and copper (.about.40 AWG wire strands) wire.

Three Dimensional Constraint Effects on the Estimated (Delta)CTOD during the Numerical Simulation of Different Fatigue Threshold Testing Techniques

NASA Technical Reports Server (NTRS)

Seshadri, Banavara R.; Smith, Stephen W.

2007-01-01

Variation in constraint through the thickness of a specimen effects the cyclic crack-tip-opening displacement (DELTA CTOD). DELTA CTOD is a valuable measure of crack growth behavior, indicating closure development, constraint variations and load history effects. Fatigue loading with a continual load reduction was used to simulate the load history associated with fatigue crack growth threshold measurements. The constraint effect on the estimated DELTA CTOD is studied by carrying out three-dimensional elastic-plastic finite element simulations. The analysis involves numerical simulation of different standard fatigue threshold test schemes to determine how each test scheme affects DELTA CTOD. The American Society for Testing and Materials (ASTM) prescribes standard load reduction procedures for threshold testing using either the constant stress ratio (R) or constant maximum stress intensity (K(sub max)) methods. Different specimen types defined in the standard, namely the compact tension, C(T), and middle cracked tension, M(T), specimens were used in this simulation. The threshold simulations were conducted with different initial K(sub max) values to study its effect on estimated DELTA CTOD. During each simulation, the DELTA CTOD was estimated at every load increment during the load reduction procedure. Previous numerical simulation results indicate that the constant R load reduction method generates a plastic wake resulting in remote crack closure during unloading. Upon reloading, this remote contact location was observed to remain in contact well after the crack tip was fully open. The final region to open is located at the point at which the load reduction was initiated and at the free surface of the specimen. However, simulations carried out using the constant Kmax load reduction procedure did not indicate remote crack closure. Previous analysis results using various starting K(sub max) values and different load reduction rates have indicated DELTA CTOD is independent of specimen size. A study of the effect of specimen thickness and geometry on the measured DELTA CTOD for various load reduction procedures and its implication in the estimation of fatigue crack growth threshold values is discussed.

Method for making generally cylindrical underground openings

DOEpatents

Routh, J.W.

1983-05-26

A rapid, economical and safe method for making a generally cylindrical underground opening such as a shaft or a tunnel is described. A borehole is formed along the approximate center line of where it is desired to make the underground opening. The borehole is loaded with an explodable material and the explodable material is detonated. An enlarged cavity is formed by the explosive action of the detonated explodable material forcing outward and compacting the original walls of the borehole. The enlarged cavity may be increased in size by loading it with a second explodable material, and detonating the second explodable material. The process may be repeated as required until the desired underground opening is made. The explodable material used in the method may be free-flowing, and it may be contained in a pipe.

Apparatus and method of capturing an orbiting spacecraft

NASA Technical Reports Server (NTRS)

Harwell, William D. (Inventor); Gardner, Dale A. (Inventor)

1987-01-01

Apparatus and a method of capturing an orbiting spacecraft by attaching a grapple fixture are discussed. A probe is inserted into an opening, such as a rocket nozzle, in the spacecraft until a stop on the prove mechanism contacts the spacecraft. A lever is actuated releasing a spring loaded rod which moves axially along the probe removing a covering sleeve to expose spring loaded toffle fingers which pivot open engaging the side of the opening. The probe is shortened and tensioned by turning a screw thread, pressing the fingers inside of the opening to compress the spacecraft between the toggle fingers and the stop. A grapple fixture attached to the probe, which is thus secured to the spacecraft, is engaged by appropriate retrieval means such as a remote manipulator arm.

Investigation of Cracks Found in Helicopter Longerons

NASA Technical Reports Server (NTRS)

Newman, John A.; Baughman, James M.; Wallace, Terryl A.

2009-01-01

Four cracked longerons, containing a total of eight cracks, were provided for study. Cracked regions were cut from the longerons. Load was applied to open the cracks, enabling crack surface examination. Examination revealed that crack propagation was driven by fatigue loading in all eight cases. Fatigue crack initiation appears to have occurred on the top edge of the longerons near geometric changes that affect component bending stiffness. Additionally, metallurigical analysis has revealed a local depletion in alloying elements in the crack initiation regions that may be a contributing factor. Fatigue crack propagation appeared to be initially driven by opening-mode loading, but at a crack length of approximately 0.5 inches (12.7 mm), there is evidence of mixed-mode crack loading. For the longest cracks studied, shear-mode displacements destroyed crack-surface features of interest over significant portions of the crack surfaces.

Investigation of Helicopter Longeron Cracks

NASA Technical Reports Server (NTRS)

Newman, John A.; Baughman, James; Wallace, Terryl A.

2009-01-01

Four cracked longerons, containing a total of eight cracks, were provided for study. Cracked regions were cut from the longerons. Load was applied to open the cracks, enabling crack surface examination. Examination revealed that crack propagation was driven by fatigue loading in all eight cases. Fatigue crack initiation appears to have occurred on the top edge of the longerons near geometric changes that affect component bending stiffness. Additionally, metallurgical analysis has revealed a local depletion in alloying elements in the crack initiation regions that may be a contributing factor. Fatigue crack propagation appeared to be initially driven by opening-mode loading, but at a crack length of approximately 0.5 inches (12.7 mm), there is evidence of mixed-mode crack loading. For the longest cracks studied, shear-mode displacements destroyed crack-surface features of interest over significant portions of the crack surfaces.

Self-Alining End Supports for Energy Absorber

NASA Technical Reports Server (NTRS)

Alfaro-Bou, E.; Eichelberger, C. P.; Fasanella, E.

1986-01-01

Simple devices stabilize axially-loaded compressive members. Energyabsorbing column held by two end supports, which stabilize column and tolerate misalinement. Column absorbs excess load by collapsing lengthwise. Self-alining supports small, lightweight, and almost maintenance-free. Their use eliminates alinement problem, opening up more applications and providing higher reliability for compressively-loaded energy absorbers.

Ported jacket for use in deformation measurement apparatus

DOEpatents

Wagner, L.A.; Senseny, P.E.; Mellegard, K.D.; Olsberg, S.B.

1990-03-06

A device for allowing deformation measurement of a jacketed specimen when the specimen is loaded includes an elastomeric specimen container or jacket surrounding a specimen while the specimen is being loaded by a test apparatus. The specimen jacket wall is compressible, and the wall follows and allows deformation of the specimen. The jacket wall of compressible material is provided with at least one opening and a thin layer or shim of substantially non-compressible (metal) material which covers and seals this opening. An extensometer is then positioned with its specimen engaging contact members engaging the substantially non-compressible material to measure the deformation of the specimen when the specimen is loaded, without compressibility effects of the jacket. 9 figs.

Two terminal micropower radar sensor

DOEpatents

McEwan, Thomas E.

1995-01-01

A simple, low power ultra-wideband radar motion sensor/switch configuration connects a power source and load to ground. The switch is connected to and controlled by the signal output of a radar motion sensor. The power input of the motion sensor is connected to the load through a diode which conducts power to the motion sensor when the switch is open. A storage capacitor or rechargeable battery is connected to the power input of the motion sensor. The storage capacitor or battery is charged when the switch is open and powers the motion sensor when the switch is closed. The motion sensor and switch are connected between the same two terminals between the source/load and ground.

Two terminal micropower radar sensor

DOEpatents

McEwan, T.E.

1995-11-07

A simple, low power ultra-wideband radar motion sensor/switch configuration connects a power source and load to ground. The switch is connected to and controlled by the signal output of a radar motion sensor. The power input of the motion sensor is connected to the load through a diode which conducts power to the motion sensor when the switch is open. A storage capacitor or rechargeable battery is connected to the power input of the motion sensor. The storage capacitor or battery is charged when the switch is open and powers the motion sensor when the switch is closed. The motion sensor and switch are connected between the same two terminals between the source/load and ground. 3 figs.

POSTOP: Postbuckled open-stiffener optimum panels-theory and capability

NASA Technical Reports Server (NTRS)

Dickson, J. N.; Biggers, S. B.

1984-01-01

The computer program POSTOP was developed to serve as an aid in the analysis and sizing of stiffened composite panels that are loaded in the postbuckling regime. A comprehensive set of analysis routines was coupled to a widely used optimization program to produce this sizing code. POSTOP is intended for the preliminary design of metal or composite panels with open-section stiffeners, subjected to multiple combined biaxial compression (or tension), shear and normal pressure load cases. Longitudinal compression, however, is assumed to be the dominant loading. Temperature, initial bow eccentricity and load eccentricity effects are included. The panel geometry is assumed to be repetitive over several bays in the longitudinal (stiffener) direction as well as in the transverse direction. Analytical routines are included to compute panel stiffnesses, strains, local and panel buckling loads, and skin/stiffener interface stresses. The resulting program is applicable to stiffened panels as commonly used in fuselage, wing, or empennage structures. The analysis procedures and rationale for the assumptions used therein are described in detail.

Building Energy Management Open Source Software

DOE Office of Scientific and Technical Information (OSTI.GOV)

This is the repository for Building Energy Management Open Source Software (BEMOSS), which is an open source operating system that is engineered to improve sensing and control of equipment in small- and medium-sized commercial buildings. BEMOSS offers the following key features: (1) Open source, open architecture – BEMOSS is an open source operating system that is built upon VOLTTRON – a distributed agent platform developed by Pacific Northwest National Laboratory (PNNL). BEMOSS was designed to make it easy for hardware manufacturers to seamlessly interface their devices with BEMOSS. Software developers can also contribute to adding additional BEMOSS functionalities and applications.more » (2) Plug & play – BEMOSS was designed to automatically discover supported load controllers (including smart thermostats, VAV/RTUs, lighting load controllers and plug load controllers) in commercial buildings. (3) Interoperability – BEMOSS was designed to work with load control devices form different manufacturers that operate on different communication technologies and data exchange protocols. (4) Cost effectiveness – Implementation of BEMOSS deemed to be cost-effective as it was built upon a robust open source platform that can operate on a low-cost single-board computer, such as Odroid. This feature could contribute to its rapid deployment in small- or medium-sized commercial buildings. (5) Scalability and ease of deployment – With its multi-node architecture, BEMOSS provides a distributed architecture where load controllers in a multi-floor and high occupancy building could be monitored and controlled by multiple single-board computers hosting BEMOSS. This makes it possible for a building engineer to deploy BEMOSS in one zone of a building, be comfortable with its operation, and later on expand the deployment to the entire building to make it more energy efficient. (6) Ability to provide local and remote monitoring – BEMOSS provides both local and remote monitoring ability with role-based access control. (7) Security – In addition to built-in security features provided by VOLTTRON, BEMOSS provides enhanced security features, including BEMOSS discovery approval process, encrypted core-to-node communication, thermostat anti-tampering feature and many more. (8) Support from the Advisory Committee – BEMOSS was developed in consultation with an advisory committee from the beginning of the project. BEMOSS advisory committee comprises representatives from 22 organizations from government and industry.« less

Numerical tools to predict the environmental loads for offshore structures under extreme weather conditions

NASA Astrophysics Data System (ADS)

Wu, Yanling

2018-05-01

In this paper, the extreme waves were generated using the open source computational fluid dynamic (CFD) tools — OpenFOAM and Waves2FOAM — using linear and nonlinear NewWave input. They were used to conduct the numerical simulation of the wave impact process. Numerical tools based on first-order (with and without stretching) and second-order NewWave are investigated. The simulation to predict force loading for the offshore platform under the extreme weather condition is implemented and compared.

Behavior of Fatigue Crack Tip Opening in Air and Corrosive Atmosphere

NASA Astrophysics Data System (ADS)

Hayashi, Morihito; Toeda, Kazunori

In the study, a formula for predicting fatigue crack tip opening displacement is deduced firstly. And then, due to comparing actual crack growth rate with the deduced formula, the crack tip configuration factor is defined to figure out the crack tip opening configuration that is useful to clarify the behavior of fatigue crack tip formation apparently. Applying the concept, the crack growth of 7/3 brass and 6/4 brass is predicted from the formula, by replacing material properties such as plastic flow resistance, Young modulus, the Poisson ratio, and fatigue toughness, and fatigue test conditions such as the stress intensity factor range, the load ratio, and cycle frequency. Furthermore, the theoretically expected results are verified with the fatigue tests which were carried out on CT specimens under different load conditions of load ratio, cycle frequency, and cyclic peak load, in different environments of air or corrosive ammonia atmosphere, for various brasses. And by comparing and discussing the calculated crack growth rate with attained experimental results, the apparent configuration factor at the crack tip is determined. And through the attained factor which changes along with crack growth, the behaviors of fatigue crack tip formation under different test conditions have been found out.

Reversing-counterpulse repetitive-pulse inductive storage circuit

DOEpatents

Honig, E.M.

1987-02-10

A high-power reversing-counterpulse repetitive-pulse inductive storage and transfer circuit includes an opening switch, a main energy storage coil, a counterpulse capacitor and a small inductor. After counterpulsing the opening switch off, the counterpulse capacitor is recharged by the main energy storage coil before the load pulse is initiated. This gives the counterpulse capacitor sufficient energy for the next counterpulse operation, although the polarity of the capacitor's voltage must be reversed before that can occur. By using a current-zero switch as the counterpulse start switch, the capacitor is disconnected from the circuit (with a full charge) when the load pulse is initiated, preventing the capacitor from depleting its energy store by discharging through the load. After the load pulse is terminated by reclosing the main opening switch, the polarity of the counterpulse capacitor voltage is reversed by discharging the capacitor through a small inductor and interrupting the discharge current oscillation at zero current and peak reversed voltage. The circuit enables high-power, high-repetition-rate operation with reusable switches and features total control (pulse-to-pulse) over output pulse initiation, duration, repetition rate, and, to some extent, risetime. 10 figs.

Loading and unloading of freeze-dryers: airborne contamination risks for aseptically manufactured sterile drug products.

PubMed

Ljungqvist, Bengt; Reinmüller, Berit

2007-01-01

In pharmaceutical manufacturing, freeze-drying processes can be adversely affected by temperature differences relative to the surrounding air. Loading and unloading of freeze-dryers are performed either without or with temperature differences between the cleanroom and the chamber of the freeze-dryer. This operation can cause a flow of room air through the opening, creating a contamination risk, especially when manual handling of material is performed in this area. To minimize this risk, a high-efficiency particulate air (HEPA) filter unit should be installed above the opening to provide clean air and protect the opening. Here the theoretical relationships are discussed and design criteria are presented.

Torsional Buckling Tests of a Simulated Solar Array

NASA Technical Reports Server (NTRS)

Thornton, E. A.

1996-01-01

Spacecraft solar arrays are typically large structures supported by long, thin deployable booms. As such, they may be particularly susceptible to abnormal structural behavior induced by mechanical and thermal loading. One example is the Hubble Space Telescope solar arrays which consist of two split tubes fit one inside the other called BiSTEMs. The original solar arrays on the Hubble Space Telescope were found to be severely twisted following deployment and later telemetry data showed the arrays were vibrating during daylight to night and night to daylight transition. The solar array twist however can force the BiSTEM booms to change in cross-section and cause tile solar arrays to react unpredictably to future loading. The solar arrays were redesigned to correct for tile vibration, however, upon redeployment they again twisted. To assess the influence of boom cross-sectional configuration, experiments were conducted on two types of booms, (1)booms with closed cross-sections, and (2) booms with open cross-sections. Both models were subjected to compressive loading and imposed tip deflections. An existing analytical model by Chung and Thornton was used to define the individual load ranges for each model solar array configuration. The load range for the model solar array using closed cross-section booms was 0-120 Newtons and 0-160 Newtons for the model solar array using open cross-section booms. The results indicate the model solar array with closed cross-section booms buckled only in flexure. However, the results of the experiment with open cross-section booms indicate the model solar array buckled only in torsion and with imposed tip deflections the cross section can degrade by rotation of the inner relative to the outer STEM. For tile Hubble Space Telescope solar arrays the results of these experiments indicate the twisting resulted from the initial mechanical loading of the open cross-section booms.

46 CFR 44.05-35 - Form of load line certificate.

Code of Federal Regulations, 2012 CFR

2012-10-01

... steamers navigate a river or inland water, deeper loading is permitted corresponding to the weight of fuel, etc., required for consumption between the point of departure and the open sea. The upper edge of the...

46 CFR 44.05-35 - Form of load line certificate.

Code of Federal Regulations, 2014 CFR

2014-10-01

... steamers navigate a river or inland water, deeper loading is permitted corresponding to the weight of fuel, etc., required for consumption between the point of departure and the open sea. The upper edge of the...

46 CFR 44.05-35 - Form of load line certificate.

Code of Federal Regulations, 2013 CFR

2013-10-01

... steamers navigate a river or inland water, deeper loading is permitted corresponding to the weight of fuel, etc., required for consumption between the point of departure and the open sea. The upper edge of the...

46 CFR 44.05-35 - Form of load line certificate.

Code of Federal Regulations, 2011 CFR

2011-10-01

... steamers navigate a river or inland water, deeper loading is permitted corresponding to the weight of fuel, etc., required for consumption between the point of departure and the open sea. The upper edge of the...

Analysis of open loop higher harmonic control at high airspeeds on a modern four-bladed articulated rotor

NASA Technical Reports Server (NTRS)

Kottapalli, Sesi; Leyland, Jane

1991-01-01

The effects of open loop higher harmonic control (HHC) on rotor hub loads, performance, and push rod loads of a Sikorsky S-76 helicopter rotor at high airspeeds (up to 200 knots) and moderate lift (10,000 lbs) were studied analytically. The analysis was performed as part of a wind tunnel pre-test prediction and preparation procedure, as well as to provide analytical results for post-test correlation efforts. The test associated with this study is to be concluded in the 40- by 80-Foot Wind Tunnel of the National Full-Scale Aerodynamics Complex (NFAC) at the NASA Ames Research Center. The results from this analytical study show that benefits from HHC can be achieved at high airspeeds. These results clear the way for conducting (with the requirement of safe pushrod loads) an open loop HHC test a high airspeeds in the 40- by 80-Foot Wind Tunnel using an S-76 rotor as the test article.

Cdt1 stabilizes an open MCM ring for helicase loading.

PubMed

Frigola, Jordi; He, Jun; Kinkelin, Kerstin; Pye, Valerie E; Renault, Ludovic; Douglas, Max E; Remus, Dirk; Cherepanov, Peter; Costa, Alessandro; Diffley, John F X

2017-06-23

ORC, Cdc6 and Cdt1 act together to load hexameric MCM, the motor of the eukaryotic replicative helicase, into double hexamers at replication origins. Here we show that Cdt1 interacts with MCM subunits Mcm2, 4 and 6, which both destabilizes the Mcm2-5 interface and inhibits MCM ATPase activity. Using X-ray crystallography, we show that Cdt1 contains two winged-helix domains in the C-terminal half of the protein and a catalytically inactive dioxygenase-related N-terminal domain, which is important for MCM loading, but not for subsequent replication. We used these structures together with single-particle electron microscopy to generate three-dimensional models of MCM complexes. These show that Cdt1 stabilizes MCM in a left-handed spiral open at the Mcm2-5 gate. We propose that Cdt1 acts as a brace, holding MCM open for DNA entry and bound to ATP until ORC-Cdc6 triggers ATP hydrolysis by MCM, promoting both Cdt1 ejection and MCM ring closure.

Cdt1 stabilizes an open MCM ring for helicase loading

PubMed Central

Frigola, Jordi; He, Jun; Kinkelin, Kerstin; Pye, Valerie E.; Renault, Ludovic; Douglas, Max E.; Remus, Dirk; Cherepanov, Peter; Costa, Alessandro; Diffley, John F. X.

2017-01-01

ORC, Cdc6 and Cdt1 act together to load hexameric MCM, the motor of the eukaryotic replicative helicase, into double hexamers at replication origins. Here we show that Cdt1 interacts with MCM subunits Mcm2, 4 and 6, which both destabilizes the Mcm2–5 interface and inhibits MCM ATPase activity. Using X-ray crystallography, we show that Cdt1 contains two winged-helix domains in the C-terminal half of the protein and a catalytically inactive dioxygenase-related N-terminal domain, which is important for MCM loading, but not for subsequent replication. We used these structures together with single-particle electron microscopy to generate three-dimensional models of MCM complexes. These show that Cdt1 stabilizes MCM in a left-handed spiral open at the Mcm2–5 gate. We propose that Cdt1 acts as a brace, holding MCM open for DNA entry and bound to ATP until ORC–Cdc6 triggers ATP hydrolysis by MCM, promoting both Cdt1 ejection and MCM ring closure. PMID:28643783

Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet

PubMed Central

Orellana, Juan A.; Busso, Dolores; Ramírez, Gigliola; Campos, Marlys; Rigotti, Attilio; Eugenín, Jaime; von Bernhardi, Rommy

2014-01-01

Nicotine, the most important neuroteratogen of tobacco smoke, can reproduce brain and cognitive disturbances per se when administered prenatally. However, it is still unknown if paracrine signaling among brain cells participates in prenatal nicotine-induced brain impairment of adult offspring. Paracrine signaling is partly mediated by unopposed channels formed by connexins hemichannels (HCs) and pannexins serving as aqueous pores permeable to ions and small signaling molecules, allowing exchange between the intra- and extracellular milieus. Our aim was to address whether prenatal nicotine exposure changes the activity of those channels in adult mice offspring under control conditions or subjected to a second challenge during young ages: high-fat/cholesterol (HFC) diet. To induce prenatal exposure to nicotine, osmotic minipumps were implanted in CF1 pregnant mice at gestational day 5 to deliver nicotine bitartrate or saline (control) solutions. After weaning, offspring of nicotine-treated or untreated pregnant mice were fed ad libitum with chow or HFC diets for 8 weeks. The functional state of connexin 43 (Cx43) and pannexin 1 (Panx1) unopposed channels was evaluated by dye uptake experiments in hippocampal slices from 11-week-old mice. We found that prenatal nicotine increased the opening of Cx43 HCs in astrocytes, and Panx1 channels in microglia and neurons only if offspring mice were fed with HFC diet. Blockade of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2) and prostaglandin E receptor 1 (EP1), ionotropic ATP receptor type 7 (P2X7) and NMDA receptors, showed differential inhibition of prenatal nicotine-induced channel opening in glial cells and neurons. Importantly, inhibition of the above mentioned enzymes and receptors, or blockade of Cx43 and Panx1 unopposed channels greatly reduced adenosine triphosphate (ATP) and glutamate release from hippocampal slices of prenatally nicotine-exposed offspring. We propose that unregulated gliotransmitter release through Cx43 and Panx1 unopposed channels may participate in brain alterations observed in offspring of mothers exposed to tobacco smoke during pregnancy. PMID:25520621

Load-Differential Features for Automated Detection of Fatigue Cracks Using Guided Waves (Preprint)

DTIC Science & Technology

2011-11-01

AFRL-RX-WP-TP-2011-4363 LOAD-DIFFERENTIAL FEATURES FOR AUTOMATED DETECTION OF FATIGUE CRACKS USING GUIDED WAVES (PREPRINT) Jennifer E...AUTOMATED DETECTION OF FATIGUE CRACKS USING GUIDED WAVES (PREPRINT) 5a. CONTRACT NUMBER FA8650-09-C-5206 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...tensile loads open fatigue cracks and thus enhance their detectability using ultrasonic methods. Here we introduce a class of load-differential methods

The Importance of Connexin Hemichannels During Chondroprogenitor Cell Differentiation in Hydrogel Versus Microtissue Culture Models

PubMed Central

Schrobback, Karsten; Klein, Travis Jacob

2015-01-01

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell–cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell–cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5′-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell–cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs. PMID:25693425

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models.

PubMed

Schrobback, Karsten; Klein, Travis Jacob; Woodfield, Tim B F

2015-06-01

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell-cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs.

Investigation of Energy-Efficient Supermarket Display Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, D.H.

Supermarkets represent one of the largest energy-intensive building groups in the commercial sector, consuming 2 to 3 million kWh/yr per store (ES-1). Over half of this energy use is for the refrigeration of food display cases and storage coolers. Display cases are used throughout a supermarket for the merchandising of perishable food products. The cases are maintained at air temperatures ranging from -10 to 35 F, depending upon the type of product stored. The operating characteristics and energy requirements of the refrigeration system are directly related to the refrigeration load. The sources of the display case refrigeration load consist of:more » (1) Moist and warm air infiltration through the open front of the case--air curtains are employed to inhibit this infiltration, but some ambient air is entrained, which adds a substantial portion to the refrigeration load. (2) Heat conduction through case panels and walls. (3) Thermal radiation from the ambient to the product and display case interior. (4) Internal thermal loads--the use of lights, evaporator fans, periodic defrosts, and antisweat heaters adds to the refrigeration load of the display case as well as directly consuming electric energy. The impact of each of these elements on the refrigeration load is very dependent upon case type (Figure ES-1). For example, air infiltration is the most significant portion of the refrigeration load for open, multi-deck cases, while radiation is the largest part of the load for tub-type cases. The door anti-sweat heaters represent a major share of the refrigeration load for frozen food door reach-in cases. Figure ES-2 shows the distribution of display cases in a typical supermarket (ES-2). Open, multi-deck, medium temperature display cases typically comprise about half of the refrigerated fixtures in a store (ES-3). In addition, medium temperature fixtures and storage coolers account for roughly 70 to 75 percent of the total store refrigeration load with open, multi-deck cases contributing about 3/4 of that fraction. Consequently, the focus of this investigation has tilted toward the open, vertical, multi-deck medium temperature case type. Various technologies and control methods are energy efficiency measures (EEMs) that could be applied to display cases and result in the reduction of the refrigeration load and of the energy consumption of the supermarket refrigeration system. An extensive evaluation of the EEMs was conducted in order to select those that met the following criteria: (1) Near-term implementation--All EEMs considered could be implemented with existing refrigeration hardware and technology. (2) Potential for energy-efficiency improvements--Energy savings and/or refrigeration load reduction must be obtained by the implementation of the EEM. (3) Enhancement of the ability to maintain target product temperature--Proper operation of the display case and maintenance of the stored product temperature could not be compromised by the use of the EEM. The energy impact of a number of viable display case EEMs was quantified by performing whole building hourly simulations. A special version of the U.S. Department of Energy's (DOE-2.3) program was used to develop a model of a supermarket. The model was then calibrated using available end-use monitored data to increase confidence in simulation results.« less

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

PubMed Central

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain.

PubMed

Pacheco-Costa, Rafael; Davis, Hannah M; Sorenson, Chad; Hon, Mary C; Hassan, Iraj; Reginato, Rejane D; Allen, Matthew R; Bellido, Teresita; Plotkin, Lilian I

2015-12-01

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. Copyright © 2015 Elsevier Inc. All rights reserved.

Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea

PubMed Central

Ceriani, Federico; Pozzan, Tullio; Mammano, Fabio

2016-01-01

Spatially and temporally coordinated variations of the cytosolic free calcium concentration ([Ca2+]c) play a crucial role in a variety of tissues. In the developing sensory epithelium of the mammalian cochlea, elevation of extracellular adenosine trisphosphate concentration ([ATP]e) triggers [Ca2+]c oscillations and propagation of intercellular inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ waves. What remains uncertain is the relative contribution of gap junction channels and connexin hemichannels to these fundamental mechanisms, defects in which impair hearing acquisition. Another related open question is whether [Ca2+]c oscillations require oscillations of the cytosolic IP3 concentration ([IP3]c) in this system. To address these issues, we performed Ca2+ imaging experiments in the lesser epithelial ridge of the mouse cochlea around postnatal day 5 and constructed a computational model in quantitative adherence to experimental data. Our results indicate that [Ca2+]c oscillations are governed by Hopf-type bifurcations within the experimental range of [ATP]e and do not require [IP3]c oscillations. The model replicates accurately the spatial extent and propagation speed of intercellular Ca2+ waves and predicts that ATP-induced ATP release is the primary mechanism underlying intercellular propagation of Ca2+ signals. The model also uncovers a discontinuous transition from propagating regimes (intercellular Ca2+ wave speed > 11 μm⋅s−1) to propagation failure (speed = 0), which occurs upon lowering the maximal ATP release rate below a minimal threshold value. The approach presented here overcomes major limitations due to lack of specific connexin channel inhibitors and can be extended to other coupled cellular systems. PMID:27807138

Biomechanical calculation of human TM joint loading with jaw opening.

PubMed

Kuboki, T; Takenami, Y; Maekawa, K; Shinoda, M; Yamashita, A; Clark, G T

2000-11-01

A three-dimensional, static mathematical calculation of the stomatognathic system was done to predict total temporomandibular joint (TMJ) loading at different levels of jaw opening. The model assumed that muscle forces acting on the mandible could be simulated by a combination of contractile components (CCs) and elastic components (ECs) and that static equilibrium existed within the body of the mandible. The model also imposed the constraint that any generated joint reaction force would act on the centre of the condyle. The results of the model demonstrated that under all conditions of opening and for all values of the elastic modulus selected, the forces between the TMJ condyle and the articular eminence were compressive in nature. The compressive force magnitude increased from 2.7 to 27.6 N incrementally as the jaw opened from 10 to 40 mm. Overall data in this study indicated that the TMJ tissues undergo low levels of compression at open positions up to 40 mm. Finally, the condition of trismus (increased jaw closing activation with opening) was simulated, the joint reaction force at 20 mm opening increased from 7.7 to 64.9 N with only a 20% activation of the closers.

Open ISEmeter: An open hardware high-impedance interface for potentiometric detection.

PubMed

Salvador, C; Mesa, M S; Durán, E; Alvarez, J L; Carbajo, J; Mozo, J D

2016-05-01

In this work, a new open hardware interface based on Arduino to read electromotive force (emf) from potentiometric detectors is presented. The interface has been fully designed with the open code philosophy and all documentation will be accessible on web. The paper describes a comprehensive project including the electronic design, the firmware loaded on Arduino, and the Java-coded graphical user interface to load data in a computer (PC or Mac) for processing. The prototype was tested by measuring the calibration curve of a detector. As detection element, an active poly(vinyl chloride)-based membrane was used, doped with cetyltrimethylammonium dodecylsulphate (CTA(+)-DS(-)). The experimental measures of emf indicate Nernstian behaviour with the CTA(+) content of test solutions, as it was described in the literature, proving the validity of the developed prototype. A comparative analysis of performance was made by using the same chemical detector but changing the measurement instrumentation.

Elastic-plastic analysis of a propagating crack under cyclic loading

NASA Technical Reports Server (NTRS)

Newman, J. C., Jr.; Armen, H., Jr.

1974-01-01

Development and application of a two-dimensional finite-element analysis to predict crack-closure and crack-opening stresses during specified histories of cyclic loading. An existing finite-element computer program which accounts for elastic-plastic material behavior under cyclic loading was modified to account for changing boundary conditions - crack growth and intermittent contact of crack surfaces. This program was subsequently used to study the crack-closure behavior under constant-amplitude and simple block-program loading.

Loading Ag nanoparticles on Cd(II) boron imidazolate framework for photocatalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Min; State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002; Zhang, De-Xiang

2016-05-15

An amine-functionalized Cd(II) boron imidazolate framework (BIF-77) with three-dimensional open structure has been successfully synthesized, which can load Ag nanoparticles (NPs) for photocatalytic degradation of methylene blue (MB). - Graphical abstract: An amine-functionalized neutral Cd(II) boron imidazolate framework can load Ag NPs and show excellent photocatalytic degradation behavious for MB. - Highlights: • Amine-functionalization. • Neutral boron imidazolate framework. • Loading Ag nanoparticles (NPs). • Photocatalytic degradation of methylene blue.

ImagingSIMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-11-06

ImagingSIMS is an open source application for loading, processing, manipulating and visualizing secondary ion mass spectrometry (SIMS) data. At PNNL, a separate branch has been further developed to incorporate application specific features for dynamic SIMS data sets. These include loading CAMECA IMS-1280, NanoSIMS and modified IMS-4f raw data, creating isotopic ratio images and stitching together images from adjacent interrogation regions. In addition to other modifications of the parent open source version, this version is equipped with a point-by-point image registration tool to assist with streamlining the image fusion process.

Strip Yield Model Numerical Application to Different Geometries and Loading Conditions

NASA Technical Reports Server (NTRS)

Hatamleh, Omar; Forman, Royce; Shivakumar, Venkataraman; Lyons, Jed

2006-01-01

A new numerical method based on the strip-yield analysis approach was developed for calculating the Crack Tip Opening Displacement (CTOD). This approach can be applied for different crack configurations having infinite and finite geometries, and arbitrary applied loading conditions. The new technique adapts the boundary element / dislocation density method to obtain crack-face opening displacements at any point on a crack, and succeeds by obtaining requisite values as a series of definite integrals, the functional parts of each being evaluated exactly in a closed form.

Theoretical study of the tunnel-boundary lift interference due to slotted walls in the presence of the trailing-vortex system of a lifting model

NASA Technical Reports Server (NTRS)

Matthews, Clarence W

1955-01-01

The equations presented in this report give the interference on the trailing-vortex system of a uniformly loaded finite-span wing in a circular tunnel containing partly open and partly closed walls, with special reference to symmetrical arrangements of the open and closed portions. Methods are given for extending the equations to include tunnel shapes other than circular. The rectangular tunnel is used to demonstrate these methods. The equations are also extended to nonuniformly loaded wings.

Status of Lake Erie phosphorus loads and concentrations

EPA Science Inventory

Under the Great Lakes Water Quality Protocol of 2012, nutrient loading and nutrient concentrations for open and nearshore waters must be re-evaluated for Substance Objectives that are consistent with overall Ecosystem Objectives. One of the primary driving nutrients of interest ...

Triggered plasma opening switch

DOEpatents

Mendel, Clifford W.

1988-01-01

A triggerable opening switch for a very high voltage and current pulse includes a transmission line extending from a source to a load and having an intermediate switch section including a plasma for conducting electrons between transmission line conductors and a magnetic field for breaking the plasma conduction path and magnetically insulating the electrons when it is desired to open the switch.

Reliable inverter systems

NASA Technical Reports Server (NTRS)

Nagano, S.

1979-01-01

Base driver with common-load-current feedback protects paralleled inverter systems from open or short circuits. Circuit eliminates total system oscillation that can occur in conventional inverters because of open circuit in primary transformer winding. Common feedback signal produced by functioning modules forces operating frequency of failed module to coincide with clock drive so module resumes normal operating frequency in spite of open circuit.

30 CFR 57.9361 - Drawholes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Loading, Hauling, and Dumping Safety Devices, Provisions, and Procedures for Roadways, Railroads, and Loading and Dumping Sites § 57.9361 Drawholes. To prevent hazards to persons underground, collars of open drawholes shall be free of...

Nanoparticles can cause DNA damage across a cellular barrier

NASA Astrophysics Data System (ADS)

Bhabra, Gevdeep; Sood, Aman; Fisher, Brenton; Cartwright, Laura; Saunders, Margaret; Evans, William Howard; Surprenant, Annmarie; Lopez-Castejon, Gloria; Mann, Stephen; Davis, Sean A.; Hails, Lauren A.; Ingham, Eileen; Verkade, Paul; Lane, Jon; Heesom, Kate; Newson, Roger; Case, Charles Patrick

2009-12-01

The increasing use of nanoparticles in medicine has raised concerns over their ability to gain access to privileged sites in the body. Here, we show that cobalt-chromium nanoparticles (29.5 +/- 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier. The damage is mediated by a novel mechanism involving transmission of purine nucleotides (such as ATP) and intercellular signalling within the barrier through connexin gap junctions or hemichannels and pannexin channels. The outcome, which includes DNA damage without significant cell death, is different from that observed in cells subjected to direct exposure to nanoparticles. Our results suggest the importance of indirect effects when evaluating the safety of nanoparticles. The potential damage to tissues located behind cellular barriers needs to be considered when using nanoparticles for targeting diseased states.

Alkaline pH sensor molecules.

PubMed

Murayama, Takashi; Maruyama, Ichiro N

2015-11-01

Animals can survive only within a narrow pH range. This requires continual monitoring of environmental and body-fluid pH. Although a variety of acidic pH sensor molecules have been reported, alkaline pH sensor function is not well understood. This Review describes neuronal alkaline pH sensors, grouped according to whether they monitor extracellular or intracellular alkaline pH. Extracellular sensors include the receptor-type guanylyl cyclase, the insulin receptor-related receptor, ligand-gated Cl- channels, connexin hemichannels, two-pore-domain K+ channels, and transient receptor potential (TRP) channels. Intracellular sensors include TRP channels and gap junction channels. Identification of molecular mechanisms underlying alkaline pH sensing is crucial for understanding how animals respond to environmental alkaline pH and how body-fluid pH is maintained within a narrow range. © 2015 Wiley Periodicals, Inc.

Testing of Action of Direct Flame on Concrete

PubMed Central

Valek, Jaroslav; Novosad, Petr

2015-01-01

The paper states results of experimental exposition of concrete test specimens to direct flame. Concrete test specimens made from various mixtures differing in the type of aggregate, binder, dispersed reinforcement, and technological procedure were subjected to thermal load. Physicomechanical and other properties of all test specimens were tested before exposition to open flame: density, compressive strength, flexural strength, moisture content, and surface appearance. The specimens were visually observed during exposition to open flame and changes were recorded. Exposed surface was photographically documented before thermal load and at 10-minute intervals. Development of temperature of the specimens was documented with a thermocamera. After exposition to thermal load and cooling down, concrete specimens were visually observed, network of cracks was photographically documented, and maximal depth of spalled area was measured. PMID:25830162

Diesel emission reduction using internal exhaust gas recirculation

DOEpatents

He, Xin [Denver, CO; Durrett, Russell P [Bloomfield Hills, MI

2012-01-24

A method for controlling combustion in a direct-injection diesel engine includes monitoring a crankshaft rotational position of a cylinder of the engine, monitoring an engine load, determining an intake stroke within the cylinder based upon the crankshaft rotational position, and when the engine load is less than a threshold engine load, opening an exhaust valve for the cylinder during a portion of the intake stroke.

Investigation of prediction methods for the loads and stresses of Apollo type spacecraft parachutes. Volume 1: Loads

NASA Technical Reports Server (NTRS)

Mickey, F. E.; Mcewan, A. J.; Ewing, E. G.; Huyler, W. C., Jr.; Khajeh-Nouri, B.

1970-01-01

An analysis was conducted with the objective of upgrading and improving the loads, stress, and performance prediction methods for Apollo spacecraft parachutes. The subjects considered were: (1) methods for a new theoretical approach to the parachute opening process, (2) new experimental-analytical techniques to improve the measurement of pressures, stresses, and strains in inflight parachutes, and (3) a numerical method for analyzing the dynamical behavior of rapidly loaded pilot chute risers.

Sensitivity and Specificity of Eustachian Tube Function Tests in Adults

PubMed Central

Doyle, William J.; Swarts, J. Douglas; Banks, Julianne; Casselbrant, Margaretha L; Mandel, Ellen M; Alper, Cuneyt M.

2013-01-01

Objective Determine if Eustachian Tube (ET) function (ETF) tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and define the inter-relatedness of ETF test parameters. Methods ETF was evaluated using the Forced-Response, Inflation-Deflation, Valsalva and Sniffing tests in 15 control ears of adult subjects after unilateral myringotomy (Group I) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (Group II). Data were analyzed using logistic regression including each parameter independently and then a step-down Discriminant Analysis including all ETF test parameters to predict group assignment. Factor Analysis operating over all parameters was used to explore relatedness. Results The Discriminant Analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency and % positive pressure equilibrated) that together correctly assigned ears to Group II at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters, the first had negative loadings of the ETF structural parameters, the second had positive loadings of the muscle-assisted ET opening parameters and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters. Discussion These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories. PMID:23868429

Interference assembly and fretting wear analysis of hollow shaft.

PubMed

Han, Chuanjun; Zhang, Jie

2014-01-01

Fretting damage phenomenon often appears in the interference fit assembly. The finite element model of hollow shaft and shaft sleeve was established, and the equivalent stress and contact stress were computed after interference assembly. The assembly body of hollow shaft and shaft sleeve was in whirling bending load, and the contact status (sticking, sliding, and opening) and the distribution of stress along one typical contact line were computed under different loads, interferences, hollow degrees, friction coefficient, and wear quantity. Judgment formula of contact state was fixed by introducing the corrected coefficient k. The computation results showed that the "edge effect" appears in the contact surface after interference fit. The size of slip zone is unchanged along with the increase of bending load. The greater the interference value, the bigger the wear range. The hollow degree does not influence the size of stick zone but controls the position of the junction point of slip-open. Tangential contact stress increases with the friction coefficient, which has a little effect on normal contact stress. The relationship between open size and wear capacity is approximately linear.

Flexural-torsional vibration of simply supported open cross-section steel beams under moving loads

NASA Astrophysics Data System (ADS)

Michaltsos, G. T.; Sarantithou, E.; Sophianopoulos, D. S.

2005-02-01

SummaryThe present work deals with linearized modal analysis of the combined flexural-torsional vibration of simply supported steel beams with open monosymmetric cross-sections, acted upon by a load of constant magnitude, traversing its span eccentrically with constant velocity. After thoroughly investigating the free vibrations of the structure, which simulates a commonly used highway bridge, its forced motions under the aforementioned loading type are investigated. Utilizing the capabilities of symbolic computations within modern mathematical software, the effect of the most significant geometrical and cross-sectional beam properties on the free vibration characteristics of the beam are established and presented in tabular and graphical form. Moreover, adopting realistic values of the simplified vehicle model adopted, the effects of eccentricity, load magnitude and corresponding velocity are assessed and interesting conclusions for structural design purposes are drawn. The proposed methodology may serve as a starting point for further in-depth study of the whole scientific subject, in which sophisticated vehicle models, energy dissipation and more complicated bridge models may be used.

Compound hydraulic shear-modulated vortex amplifiers

NASA Technical Reports Server (NTRS)

Goldschmied, F. R.

1977-01-01

A novel two-stage shear-modulated hydraulic vortex amplifier (U.S. patent 3,520,317) has been fabricated and put through preliminary steady-state testing at the 1000 psi supply pressure level with flows up to 15 gpm. The invention comprises a conventional fluidic vortex power stage and a shear-modulated pilot stage. In the absence of any mechanical moving parts, water may be used as the hydraulic medium thus opening the way to many underseas applications. At blocked load, a control input from 0 to 150 psi was required to achieve an output from 0 to 900 psi; at wide-open load, a control input of 0 to 120 psi was needed to achieve an output from 0 to 15 gpm. The power stage has been found unsuitable for the proportional control mode because of its nonlinear performance in the intermediate load range and because of strong pressure fluctuations (plus or minus 150 psi) in the intermediate control range. The addition of the shear-modulated pilot stage improves intermediate load linearity.

Effect of Impact Damage and Open Hole on Compressive Strength of Hybrid Composite Laminates

NASA Technical Reports Server (NTRS)

Hiel, Clement; Brinson, H. F.

1993-01-01

Impact damage tolerance is a frequently listed design requirement for composites hardware. The effect of impact damage and open hole size on laminate compressive strength was studied on sandwich beam specimens which combine CFRP-GFRP hybrid skins and a syntactic foam core. Three test specimen configurations have been investigated for this study. The first two were sandwich beams which were loaded in pure bending (by four point flexure). One series had a skin damaged by impact, and the second series had a circular hole machined through one of the skins. The reduction of compressive strength with increasing damage (hole) size was compared. Additionally a third series of uniaxially loaded open hole compression coupons were tested to generate baseline data for comparison with both series of sandwich beams.

Foil system fatigue load environments for commercial hydrofoil operation

NASA Technical Reports Server (NTRS)

Graves, D. L.

1979-01-01

The hydrofoil fatigue loads environment in the open sea is examined. The random nature of wave orbital velocities, periods and heights plus boat heading, speed and control system design are considered in the assessment of structural fatigue requirements. Major nonlinear load events such as hull slamming and foil unwetting are included in the fatigue environment. Full scale rough water load tests, field experience plus analytical loads work on the model 929 Jetfoil commercial hydrofoil are discussed. The problem of developing an overall sea environment for design is defined. State of the art analytical approaches are examined.

Squat Biomechanical Modeling Results from Exercising on the Hybrid Ultimate Lifting Kit

NASA Technical Reports Server (NTRS)

Gallo, Christopher A.; Thompson, William K.; Lewandowski, Beth E.; Jagodnik, Kathleen M.

2016-01-01

Long duration space travel will expose astronauts to extended periods of reduced gravity. Since gravity is not present to aid loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft is limited and therefore compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Biomechanical data collection and computational modeling aid the device design process by quantifying the joint torques and the musculoskeletal forces that occur during exercises performed on the prototype devices. The computational models currently under development utilize the OpenSim software, an open source code for musculoskeletal modeling, with biomechanical input data from test subjects for estimation of muscle and joint loads. The subjects are instrumented with reflective markers for motion capture data collection while exercising on the Hybrid Ultimate Lifting Kit (HULK) prototype device. Ground reaction force data is collected with force plates under the feet and device loading is recorded through load cells internal to the HULK. Test variables include applied device load, narrow or wide foot stance, slow or fast cadence and the harness or long bar interface between the test subject and the device. Data is also obtained using free weights for a comparison to the resistively loaded exercise device. This data is input into the OpenSim biomechanical model, which has been scaled to match the anthropometrics of the test subject, to calculate the body loads. The focus of this presentation is to summarize the results from the full squat exercises across the different test variables.

The effect of open kinetic chain knee extensor resistance training at different training loads on anterior knee laxity in the uninjured.

PubMed

Barcellona, Massimo G; Morrissey, Matthew C

2016-04-01

The commonly used open kinetic chain knee extensor (OKCKE) exercise loads the sagittal restraints to knee anterior tibial translation. To investigate the effect of different loads of OKCKE resistance training on anterior knee laxity (AKL) in the uninjured knee. non-clinical trial. Randomization into one of three supervised training groups occurred with training 3 times per week for 12 weeks. Subjects in the LOW and HIGH groups performed OKCKE resistance training at loads of 2 sets of 20 repetition maximum (RM) and 20 sets of 2RM, respectively. Subjects in the isokinetic training group (ISOK) performed isokinetic OKCKE resistance training using 2 sets of 20 maximal efforts. AKL was measured using the KT2000 arthrometer with concurrent measurement of lateral hamstrings muscle activity at baseline, 6 weeks and 12 weeks. Twenty six subjects participated (LOW n = 9, HIGH n = 10, ISOK n = 7). The main finding from this study is that a 12-week OKCKE resistance training programme at loads of 20 sets of 2RM, leads to an increase in manual maximal AKL. OKCKE resistance training at high loads (20 sets of 2RM) increases AKL while low load OKCKE resistance training (2 sets of 20RM) and isokinetic OKCKE resistance training at 2 sets of 20RM does not. Copyright © 2015 Elsevier Ltd. All rights reserved.

Symphyseal fixation in open book injuries cannot fully compensate anterior SI joint injury-A biomechanical study in a two-leg alternating load model.

PubMed

Stuby, Fabian M; Lenz, Mark; Doebele, Stefan; Agarwal, Yash; Skulev, Hristo; Ochs, Björn G; Zwingmann, Jörn; Gueorguiev, Boyko

2017-01-01

In open book injuries type Tile B1.1 or B1.2 also classified as APC II (anteroposterior compression), it remains controversial, if a fixation of the anterior ring provides sufficient stability or a fixation of the posterior ring should be included. Therefore the relative motion at the sacroiliac joint was quantified in a two-leg alternating load biomechanical pelvis model in the intact, the injured and the restored pelvis. Fresh-frozen intact (I) pelvises (n = 6) were subjected to a non-destructive cyclic test under sinosuidal axial two-leg alternating load with progressively increasing amplitude. Afterwards an open book injury (J) including the anterior ligament complex of the left sacroiliac joint, the sacrospinal and sacrotuberal ligaments (Tile B1.1) was created and the specimens were retested. Finally, the symphysis was stabilized with a modular fixation system (1-, 2- or 4-rod configuration) (R) and specimens were cyclically retested. Relative motion at the sacroiliac joint was captured at both sacroiliac joints by motion tracking system at two load levels of 170 N and 340 N during all tests. Relative sacroiliac joint movements at both load levels were significantly higher in the J-state compared to the I-state, excluding superoinferior translational movement. With exception of the anteroposterior translational movement at 340N, the relative sacroiliac joint movements after each of the three reconstructions (1-, 2-, 4-rod fixation) were significantly smaller compared to the J-state and did not differ significantly to the I-state, but stayed above the values of the latter. Relative movements did not differ significantly in a direct comparison between the 1-rod, 2-rod and 4-rod fixations. Symphyseal locked plating significantly reduces relative movement of the sacroiliac joint in open book injuries type Tile B1.1 or B1.2 (APC II) but cannot fully restore the situation of the intact sacroiliac joint.

Symphyseal fixation in open book injuries cannot fully compensate anterior SI joint injury—A biomechanical study in a two-leg alternating load model

PubMed Central

Stuby, Fabian M.; Lenz, Mark; Agarwal, Yash; Skulev, Hristo; Ochs, Björn G.; Zwingmann, Jörn; Gueorguiev, Boyko

2017-01-01

Introduction In open book injuries type Tile B1.1 or B1.2 also classified as APC II (anteroposterior compression), it remains controversial, if a fixation of the anterior ring provides sufficient stability or a fixation of the posterior ring should be included. Therefore the relative motion at the sacroiliac joint was quantified in a two-leg alternating load biomechanical pelvis model in the intact, the injured and the restored pelvis. Methods Fresh-frozen intact (I) pelvises (n = 6) were subjected to a non-destructive cyclic test under sinosuidal axial two-leg alternating load with progressively increasing amplitude. Afterwards an open book injury (J) including the anterior ligament complex of the left sacroiliac joint, the sacrospinal and sacrotuberal ligaments (Tile B1.1) was created and the specimens were retested. Finally, the symphysis was stabilized with a modular fixation system (1-, 2- or 4-rod configuration) (R) and specimens were cyclically retested. Relative motion at the sacroiliac joint was captured at both sacroiliac joints by motion tracking system at two load levels of 170 N and 340 N during all tests. Results Relative sacroiliac joint movements at both load levels were significantly higher in the J-state compared to the I-state, excluding superoinferior translational movement. With exception of the anteroposterior translational movement at 340N, the relative sacroiliac joint movements after each of the three reconstructions (1-, 2-, 4-rod fixation) were significantly smaller compared to the J-state and did not differ significantly to the I-state, but stayed above the values of the latter. Relative movements did not differ significantly in a direct comparison between the 1-rod, 2-rod and 4-rod fixations. Conclusion Symphyseal locked plating significantly reduces relative movement of the sacroiliac joint in open book injuries type Tile B1.1 or B1.2 (APC II) but cannot fully restore the situation of the intact sacroiliac joint. PMID:29176772

A state of the art review on reinforced concrete beams with openings retrofitted with FRP

NASA Astrophysics Data System (ADS)

Osman, Bashir H.; Wu, Erjun; Ji, Bohai; S Abdelgader, Abdeldime M.

2016-09-01

The use of externally bonded fiber reinforced polymer (FRP) sheets, strips or steel plates is a modern and convenient way for strengthening of reinforced concrete (RC) beams. Several researches have been carried out on reinforced concrete beams with web openings that strengthened using fiber reinforced polymer composite. Majority of researches focused on shear strengthening compared with flexural strengthening, while others studied the effect of openings on shear and flexural separately with various loading. This paper investigates the impact of more than sixty articles on opening reinforced concrete beams with and without strengthening by fiber reinforcement polymers FRP. Moreover, important practical issues, which are contributed in shear strengthening of beams with different strengthening techniques, such as steel plate and FRP laminate, and detailed with various design approaches are discussed. Furthermore, a simple technique of applying fiber reinforced polymer contributed with steel plate for strengthening the RC beams with openings under different load application is concluded. Directions for future research based on the existing gaps of the present works are presented.

NEUTRONIC REACTOR SHIELD AND SPACER CONSTRUCTION

DOEpatents

Wigner, E.P.; Ohlinger, L.A.

1958-11-18

Reactors of the heterogeneous, graphite moderated, fluid cooled type and shielding and spacing plugs for the coolant channels thereof are reported. In this design, the coolant passages extend horizontally through the moderator structure, accommodating the fuel elements in abutting end-to-end relationship, and have access openings through the outer shield at one face of the reactor to facilitate loading of the fuel elements. In the outer ends of the channels which extend through the shields are provided spacers and shielding plugs designed to offer minimal reslstance to coolant fluid flow while preventing emanation of harmful radiation through the access openings when closed between loadings.

Dividers for reduction of aerodynamic drag of vehicles with open cavities

NASA Technical Reports Server (NTRS)

Storms, Bruce L. (Inventor)

2007-01-01

A drag-reduction concept for vehicles with open cavities includes dividing a cavity into smaller adjacent cavities through installation of one or more vertical dividers. The dividers may extend the full depth of the cavity or only partial depth. In either application, the top of the dividers are typically flush with the top of the bed or cargo bay of the vehicle. The dividers may be of any material, but are strong enough for both wind loads and forces encountered during cargo loading/unloading. For partial depth dividers, a structural angle may be desired to increase strength.

Real-time volume rendering of 4D image using 3D texture mapping

NASA Astrophysics Data System (ADS)

Hwang, Jinwoo; Kim, June-Sic; Kim, Jae Seok; Kim, In Young; Kim, Sun Il

2001-05-01

Four dimensional image is 3D volume data that varies with time. It is used to express deforming or moving object in virtual surgery of 4D ultrasound. It is difficult to render 4D image by conventional ray-casting or shear-warp factorization methods because of their time-consuming rendering time or pre-processing stage whenever the volume data are changed. Even 3D texture mapping is used, repeated volume loading is also time-consuming in 4D image rendering. In this study, we propose a method to reduce data loading time using coherence between currently loaded volume and previously loaded volume in order to achieve real time rendering based on 3D texture mapping. Volume data are divided into small bricks and each brick being loaded is tested for similarity to one which was already loaded in memory. If the brick passed the test, it is defined as 3D texture by OpenGL functions. Later, the texture slices of the brick are mapped into polygons and blended by OpenGL blending functions. All bricks undergo this test. Continuously deforming fifty volumes are rendered in interactive time with SGI ONYX. Real-time volume rendering based on 3D texture mapping is currently available on PC.

The role of water management on the oxygen transport resistance in polymer electrolyte fuel cell with ultra-low precious metal loading

NASA Astrophysics Data System (ADS)

Srouji, A. K.; Zheng, L. J.; Dross, R.; Aaron, D.; Mench, M. M.

2017-10-01

Limiting current measurements are used to evaluate oxygen transport resistance in the catalyst layer of a polymer electrolyte fuel cell (PEFC). The pressure independent oxygen transport resistance in the electrode is quantified for two cell architectures and two cathode Pt loadings (0.4 and 0.07 mgPt.cm-2). The compounded effect of the flow field and Pt loading is used to shed light on the nature of the observed transport resistance, especially its response to fundamentally different flow fields, which is shown to directly or indirectly scale with Pt loading in the open literature. By varying gas pressure and using low oxygen concentrations, the total oxygen transport resistance is divided into intermolecular gas diffusion (a pressure-dependent component) and a pressure independent component, which can be attributed to Knudsen diffusion or dissolution film resistance. The pressure-independent oxygen transport resistance in the catalyst layer varies between 13.3 and 34.4 s/m. It is shown that the pressure independent oxygen transport resistance increases with reduced Pt loading, but that effect is greatly exacerbated by using conventional channel/lands. The results indicate that open metallic element architecture improves the oxygen transport resistance in ultra-low Pt loading electrodes, likely due to enhanced water management at the catalyst layer.

Valve for fuel pin loading system

DOEpatents

Christiansen, David W.

1985-01-01

A cyclone valve surrounds a wall opening through which cladding is projected. An axial valve inlet surrounds the cladding. Air is drawn through the inlet by a cyclone stream within the valve. An inflatable seal is included to physically engage a fuel pin subassembly during loading of fuel pellets.

A pilot hole does not reduce the strains or risk of fracture to the lateral cortex during and following a medial opening wedge high tibial osteotomy in cadaveric specimens.

PubMed

Bujnowski, K; Getgood, A; Leitch, K; Farr, J; Dunning, C; Burkhart, T A

2018-02-01

It has been suggested that the use of a pilot-hole may reduce the risk of fracture to the lateral cortex. Therefore the purpose of this study was to determine the effect of a pilot hole on the strains and occurrence of fractures at the lateral cortex during the opening of a high tibial osteotomy (HTO) and post-surgery loading. A total of 14 cadaveric tibias were randomized to either a pilot hole (n = 7) or a no-hole (n = 7) condition. Lateral cortex strains were measured while the osteotomy was opened 9 mm and secured in place with a locking plate. The tibias were then subjected to an initial 800 N load that increased by 200 N every 5000 cycles, until failure or a maximum load of 2500 N. There was no significant difference in the strains on the lateral cortex during HTO opening between the pilot hole and no-hole conditions. Similarly, the lateral cortex and fixation plate strains were not significantly different during cyclic loading between the two conditions. Using a pilot hole did not significantly decrease the strains experienced at the lateral cortex, nor did it reduce the risk of fracture. The nonsignificant differences found here most likely occurred because the pilot hole merely translated the stress concentration laterally to a parallel point on the surface of the hole. Cite this article : K. Bujnowski, A. Getgood, K. Leitch, J. Farr, C. Dunning, T. A. Burkhart. A pilot hole does not reduce the strains or risk of fracture to the lateral cortex during and following a medial opening wedge high tibial osteotomy in cadaveric specimens. Bone Joint Res 2018;7:166-172. DOI: 10.1302/2046-3758.72.BJR-2017-0337.R1.

A Relationship Between Constraint and the Critical Crack Tip Opening Angle

NASA Technical Reports Server (NTRS)

Johnston, William M.; James, Mark A.

2009-01-01

Of the various approaches used to model and predict fracture, the Crack Tip Opening Angle (CTOA) fracture criterion has been successfully used for a wide range of two-dimensional thin-sheet and thin plate applications. As thicker structure is considered, modeling the full three-dimensional fracture process will become essential. This paper investigates relationships between the local CTOA evaluated along a three-dimensional crack front and the corresponding local constraint. Previously reported tunneling crack front shapes were measured during fracture by pausing each test and fatigue cycling the specimens to mark the crack surface. Finite element analyses were run to model the tunneling shape during fracture, with the analysis loading conditions duplicating those tests. The results show an inverse relationship between the critical fracture value and constraint which is valid both before maximum load and after maximum load.

Comparison of Hydrodynamic Load Predictions Between Engineering Models and Computational Fluid Dynamics for the OC4-DeepCwind Semi-Submersible: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benitz, M. A.; Schmidt, D. P.; Lackner, M. A.

Hydrodynamic loads on the platforms of floating offshore wind turbines are often predicted with computer-aided engineering tools that employ Morison's equation and/or potential-flow theory. This work compares results from one such tool, FAST, NREL's wind turbine computer-aided engineering tool, and the computational fluid dynamics package, OpenFOAM, for the OC4-DeepCwind semi-submersible analyzed in the International Energy Agency Wind Task 30 project. Load predictions from HydroDyn, the offshore hydrodynamics module of FAST, are compared with high-fidelity results from OpenFOAM. HydroDyn uses a combination of Morison's equations and potential flow to predict the hydrodynamic forces on the structure. The implications of the assumptionsmore » in HydroDyn are evaluated based on this code-to-code comparison.« less

NEUTRONIC REACTORS

DOEpatents

Wigner, E.P.; Young, G.J.

1958-10-14

A method is presented for loading and unloading rod type fuel elements of a neutronic reactor of the heterogeneous, solld moderator, liquid cooled type. In the embodiment illustrated, the fuel rods are disposed in vertical coolant channels in the reactor core. The fuel rods are loaded and unloaded through the upper openings of the channels which are immersed in the coolant liquid, such as water. Unloading is accomplished by means of a coffer dam assembly having an outer sleeve which is placed in sealing relation around the upper opening. A radiation shield sleeve is disposed in and reciprocable through the coffer dam sleeve. A fuel rod engaging member operates through the axial bore in the radiation shield sleeve to withdraw the fuel rod from its position in the reactor coolant channel into the shield, the shield snd rod then being removed. Loading is accomplished in the reverse procedure.

Cylindrical Shells Made of Stainless Steel - Investigation of Postbuckling

NASA Astrophysics Data System (ADS)

Stehr, Sebastian; Stranghöner, Natalie

2017-06-01

The relevant load case of open thin-walled shells is often wind loading during construction. Because of the missing stabilization effect of the roof they show a very high sensitivity to buckling which results into higher wall thicknesses. As part of the European RFCS research project BiogaSS the Institute for Metal and Lightweight Structures of the University of Duisburg-Essen carried out investigations on open thin-walled tanks made of austenitic and duplex stainless steels under wind load to study a possible economic advantage which might be gained from the consideration of the elastic postbuckling behaviour. This contribution presents not only experimental and numerical results but also first recommendations regarding the range of possible buckling reduction factors which might be incorporated in future revisions of EN 1993-1-6 and EN 1993-4-2.

Assessment of Optimal Flexibility in Ensemble of Frequency Responsive Loads

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kundu, Soumya; Hansen, Jacob; Lian, Jianming

2018-04-19

Potential of electrical loads in providing grid ancillary services is often limited due to the uncertainties associated with the load behavior. A knowledge of the expected uncertainties with a load control program would invariably yield to better informed control policies, opening up the possibility of extracting the maximal load control potential without affecting grid operations. In the context of frequency responsive load control, a probabilistic uncertainty analysis framework is presented to quantify the expected error between the target and actual load response, under uncertainties in the load dynamics. A closed-form expression of an optimal demand flexibility, minimizing the expected errormore » in actual and committed flexibility, is provided. Analytical results are validated through Monte Carlo simulations of ensembles of electric water heaters.« less

Characterizing the Collagen Fiber Orientation in Pericardial Leaflets Under Mechanical Loading Conditions

PubMed Central

Alavi, S. Hamed; Ruiz, Victor; Krasieva, Tatiana; Botvinick, Elliot L.; Kheradvar, Arash

2014-01-01

When implanted inside the body, bioprosthetic heart valve leaflets experience a variety of cyclic mechanical stresses such as shear stress due to blood flow when the valve is open, flexural stress due to cyclic opening and closure of the valve, and tensile stress when the valve is closed. These types of stress lead to a variety of failure modes. In either a natural valve leaflet or a processed pericardial tissue leaflet, collagen fibers reinforce the tissue and provide structural integrity such that the very thin leaflet can stand enormous loads related to cyclic pressure changes. The mechanical response of the leaflet tissue greatly depends on collagen fiber concentration, characteristics, and orientation. Thus, understating the microstructure of pericardial tissue and its response to dynamic loading is crucial for the development of more durable heart valve, and computational models to predict heart valves’ behavior. In this work, we have characterized the 3D collagen fiber arrangement of bovine pericardial tissue leaflets in response to a variety of different loading conditions under Second-Harmonic Generation Microscopy. This real-time visualization method assists in better understanding of the effect of cyclic load on collagen fiber orientation in time and space. PMID:23180029

49 CFR 174.114 - Record to be made of change of seals on “Cars loaded with Division 1.1 or 1.2 (explosive...

Code of Federal Regulations, 2010 CFR

2010-10-01

... car to its destination: RailroadPlaceDate Car InitialsCar NumberNumber or description of seal broken Number or description of seal used to reseal car Reasons for opening car Condition of load Name and...

40 CFR 63.923 - Standards-Container Level 2 controls.

Code of Federal Regulations, 2012 CFR

2012-07-01

... will be added to the container within 15 minutes, the person performing the loading operation leaves... minutes or the person performing the unloading operation leaves the immediate vicinity of the container...) Opening of a spring-loaded pressure-vacuum relief valve, conservation vent, or similar type of pressure...

40 CFR 63.923 - Standards-Container Level 2 controls.

Code of Federal Regulations, 2014 CFR

2014-07-01

... will be added to the container within 15 minutes, the person performing the loading operation leaves... minutes or the person performing the unloading operation leaves the immediate vicinity of the container...) Opening of a spring-loaded pressure-vacuum relief valve, conservation vent, or similar type of pressure...

40 CFR 63.923 - Standards-Container Level 2 controls.

Code of Federal Regulations, 2011 CFR

2011-07-01

... will be added to the container within 15 minutes, the person performing the loading operation leaves... minutes or the person performing the unloading operation leaves the immediate vicinity of the container...) Opening of a spring-loaded pressure-vacuum relief valve, conservation vent, or similar type of pressure...

40 CFR 63.923 - Standards-Container Level 2 controls.

Code of Federal Regulations, 2013 CFR

2013-07-01

... will be added to the container within 15 minutes, the person performing the loading operation leaves... minutes or the person performing the unloading operation leaves the immediate vicinity of the container...) Opening of a spring-loaded pressure-vacuum relief valve, conservation vent, or similar type of pressure...

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

30 CFR 75.815 - Disconnect devices.

Code of Federal Regulations, 2011 CFR

2011-07-01

... phase-to-phase voltage of the circuit in which they are installed, and for the full-load current of the... explosion-proof enclosures, must be capable of interrupting the full-load current of the circuit or designed and installed to cause the current to be interrupted automatically prior to the opening of the...

30 CFR 75.815 - Disconnect devices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... phase-to-phase voltage of the circuit in which they are installed, and for the full-load current of the... explosion-proof enclosures, must be capable of interrupting the full-load current of the circuit or designed and installed to cause the current to be interrupted automatically prior to the opening of the...

Opening Switch Research on a Dense Plasma Focus.

DTIC Science & Technology

Several experiments were performed to enhance power coupling to the load by placing the load electrode opposite the muzzle end of the Dense Plasma ... Focus plasma gun. The impaler concept, whereby the current sheath is run into a knife edge insulator, was tested in two configurations. However, the

Open ISEmeter: An open hardware high-impedance interface for potentiometric detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salvador, C.; Carbajo, J.; Mozo, J. D., E-mail: jdaniel.mozo@diq.uhu.es

In this work, a new open hardware interface based on Arduino to read electromotive force (emf) from potentiometric detectors is presented. The interface has been fully designed with the open code philosophy and all documentation will be accessible on web. The paper describes a comprehensive project including the electronic design, the firmware loaded on Arduino, and the Java-coded graphical user interface to load data in a computer (PC or Mac) for processing. The prototype was tested by measuring the calibration curve of a detector. As detection element, an active poly(vinyl chloride)-based membrane was used, doped with cetyltrimethylammonium dodecylsulphate (CTA{sup +}-DS{supmore » −}). The experimental measures of emf indicate Nernstian behaviour with the CTA{sup +} content of test solutions, as it was described in the literature, proving the validity of the developed prototype. A comparative analysis of performance was made by using the same chemical detector but changing the measurement instrumentation.« less

Biomechanical Modeling of Split-leg Squat and Heel Raise on the Hybrid Ultimate Lifting Kit (HULK)

NASA Technical Reports Server (NTRS)

Thompson, William K.; Gallo, Christopher A.; Lewandowski, Beth E.; Jagodnik, Kathleen M.; Humphreys, Brad; Funk, Justin; Funk, Nathan; Dewitt, John K.

2016-01-01

Long duration space travel will expose astronauts to extended periods of reduced gravity. Since gravity is not present to aid loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft is limited and therefore compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Biomechanical data collection and computational modeling aid the device design process by quantifying the joint torques and musculoskeletal forces that occur during exercises performed on the prototype devices. Computational models currently use OpenSim software, an open source code for musculoskeletal modeling, with biomechanical input data from subjects for estimation of muscle and joint loads. Subjects are instrumented with reflective markers for motion capture data collection while exercising on the Hybrid Ultimate Lifting Kit (HULK) prototype device. Ground reaction force data is collected with force plates under the feet and device loading is recorded through load cells internal to the HULK. This data is input into the OpenSim biomechanical model, which has been scaled to match the anthropometrics of the test subject, to calculate the loads on the body. Multiple exercises are performed and evaluated during a test session such as a full squat, single leg squat, heel raise and dead lift. Variables for these exercises include applied device load, narrow or wide foot stance, slow or fast cadence and the harness or long bar interface between the test subject and the device. Data from free weights are compared to the resistively loaded exercise device. The focus of this presentation is to summarize the results from the single-leg squat and heel raise exercises performed during three sessions occurring in 2015. Differences in loading configuration, cadence and stance produce differences in kinematics, joint toques and force and muscle forces.

Dynamic Response of Acrylonitrile Butadiene Styrene Under Impact Loading (Open Access)

DTIC Science & Technology

2016-03-16

of contraction and expansion was observed as the impact load was applied. Thismultistage deformation behavior may be attributable to the ring formed ...ABS fabricated by FDM. Results of the experimental characterization show that rasters formed parallel to the loading direction fabricated in the... formed using a solid ABS block to determine the mechanical property at various strain rates (Fig. 1). Through the analysis of the solid ABS, a linear

Characterization and tropical seasonal variation of leachate: results from landfill lysimeter studied.

PubMed

Rafizul, Islam M; Alamgir, Muhammed

2012-11-01

This study aims to characterize the leachate and to investigate the tropical climatic influence on leachate characteristics of lysimeter studies under different seasonal variations at KUET campus, Bangladesh. Three different situations of landfill were considered here as well as both the open dump lysimeter-A having a base liner and sanitary landfill lysimeter-B and C at two different types of cap liner were simulated. The leachate characteristics, leachate generation and climatic influence parameter had been continually monitored since June 2008 to May 2010, these periods cover both the dry and rainy season. The leachate generation had followed the rainfall pattern and the open dump lysimeter-A without top cover was recorded to have highest leachate generation. Moreover, the open dump lysimeter-A had lower total kjeldahl nitrogen (TKN), ammonia nitrogen (NH(4)-N) and TKN load, while both the COD concentration and load was higher compared with sanitary landfill lysimeter-B and C. In addition, sanitary landfill lysimeter-B, not only had lowest leachate generation, but also produces reasonable low COD concentration and load compared with open dump lysimeter-A. Result reveals that lysimeter operational mode had direct effect on leachate quality. Finally, it can be concluded that the knowledge of leachate quality will be useful in planning and providing remedial measures of proper liner system in sanitary landfill design and leachate treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Experimental data on load test and performance parameters of a LENZ type vertical axis wind turbine in open environment condition.

PubMed

Sivamani, Seralathan; T, Micha Premkumar; Sohail, Mohammed; T, Mohan; V, Hariram

2017-12-01

Performance and load testing data of a three bladed two stage LENZ type vertical axis wind turbine from the experiments conducted in an open environment condition at Hindustan Institute of Technology and Science, Chennai (location 23.2167°N, 72.6833°E) are presented here. Low-wind velocity ranging from 2 to 11 m/s is available everywhere irrespective of climatic seasons and this data provides the support to the researchers using numerical tool to validate and develop an enhanced Lenz type design. Raw data obtained during the measurements are processed and presented in the form so as to compare with other typical outputs. The data is measured at different wind speeds prevalent in the open field condition ranging from 3 m/s to 9 m/s.

LAKE MICHIGAN MASS BALANCE STUDY UPDATE

EPA Science Inventory

A 2005 field design of tributary and open Lake Michigan sampling will be discussed for the first time at this Council meeting. The sample design is expected to aid in determining whether or not contaminant loads and open lake concentrations have decreased over the past 10 years s...

Restrike Particle Beam Experiments on a Dense Plasma Focus. Opening Switch Research on a Dense Plasma Focus.

DTIC Science & Technology

1985-06-01

Research on this grant has focused on plasma focus experiments in the areas of particle beam generation and as a potential repetitive opening switch...as were scaling laws for the increase of electron energy and current with input energy. The potential of the plasma focus as an opening switch was...delay line technique. The observed frequencies were most consistent with the lower hybrid frequency. Keywords include: Dense Plasma Focus , Particle Beam Generation, Opening Switch, Load Experiments, Pulsed Power.

Connexin-Mediated Functional and Metabolic Coupling Between Astrocytes and Neurons.

PubMed

Mayorquin, Lady C; Rodriguez, Andrea V; Sutachan, Jhon-Jairo; Albarracín, Sonia L

2018-01-01

The central nervous system (CNS) requires sophisticated regulation of neuronal activity. This modulation is partly accomplished by non-neuronal cells, characterized by the presence of transmembrane gap junctions (GJs) and hemichannels (HCs). This allows small molecule diffusion to guarantee neuronal synaptic activity and plasticity. Astrocytes are metabolically and functionally coupled to neurons by the uptake, binding and recycling of neurotransmitters. In addition, astrocytes release metabolites, such as glutamate, glutamine, D-serine, adenosine triphosphate (ATP) and lactate, regulating synaptic activity and plasticity by pre- and postsynaptic mechanisms. Uncoupling neuroglial communication leads to alterations in synaptic transmission that can be detrimental to neuronal circuit function and behavior. Therefore, understanding the pathways and mechanisms involved in this intercellular communication is fundamental for the search of new targets that can be used for several neurological disease treatments. This review will focus on molecular mechanisms mediating physiological and pathological coupling between astrocytes and neurons through GJs and HCs.

Load apparatus and method for bolt-loaded compact tension test specimen

DOEpatents

Buescher, B.J. Jr.; Lloyd, W.R.; Ward, M.B.; Epstein, J.S.

1997-02-04

A bolt-loaded compact tension test specimen load apparatus includes: (a) a body having first and second opposing longitudinal ends, the first end comprising an externally threaded portion sized to be threadedly received within the test specimen threaded opening; (b) a longitudinal loading rod having first and second opposing longitudinal ends, the loading rod being slidably received in a longitudinal direction within the body internally through the externally threaded portion and slidably extending longitudinally outward of the body first longitudinal end; (c) a force sensitive transducer slidably received within the body and positioned to engage relative to the loading rod second longitudinal end; and (d) a loading bolt threadedly received relative to the body, the loading bolt having a bearing end surface and being positioned to bear against the transducer to forcibly sandwich the transducer between the loading bolt and loading rod. Also disclosed is a method of in situ determining applied force during crack propagation in a bolt-loaded compact tension test specimen. 6 figs.

Load apparatus and method for bolt-loaded compact tension test specimen

DOEpatents

Buescher, Jr., Brent J.; Lloyd, W. Randolph; Ward, Michael B.; Epstein, Jonathan S.

1997-01-01

A bolt-loaded compact tension test specimen load apparatus includes: a) a body having first and second opposing longitudinal ends, the first end comprising an externally threaded portion sized to be threadedly received within the test specimen threaded opening; b) a longitudinal loading rod having first and second opposing longitudinal ends, the loading rod being slidably received in a longitudinal direction within the body internally through the externally threaded portion and slidably extending longitudinally outward of the body first longitudinal end; c) a force sensitive transducer slidably received within the body and positioned to engage relative to the loading rod second longitudinal end; and d) a loading bolt threadedly received relative to the body, the loading bolt having a bearing end surface and being positioned to bear against the transducer to forcibly sandwich the transducer between the loading bolt and loading rod. Also disclosed is a method of in situ determining applied force during crack propagation in a bolt-loaded compact tension test specimen.

Large-Eddy Simulation of Propeller Crashback

NASA Astrophysics Data System (ADS)

Kumar, Praveen; Mahesh, Krishnan

2013-11-01

Crashback is an operating condition to quickly stop a propelled vehicle, where the propeller is rotated in the reverse direction to yield negative thrust. The crashback condition is dominated by the interaction of free stream flow with strong reverse flow. Crashback causes highly unsteady loads and flow separation on blade surface. This study uses Large-Eddy Simulation to predict the highly unsteady flow field in propeller crashback. Results are shown for a stand-alone open propeller, hull-attached open propeller and a ducted propeller. The simulations are compared to experiment, and used to discuss the essential physics behind the unsteady loads. This work is supported by the Office of Naval Research.

Automatically operable self-leveling load table

NASA Technical Reports Server (NTRS)

Burch, J. L. (Inventor)

1974-01-01

A self-leveling load table is described which is automatically maintained level by selectively opening and closing solenoid valves for inserting and removing air from chambers under the table. The table is floated in a fluid by nine air chambers beneath the top of the table. These chambers are open at the bottom and four oppositely located chambers are used for leveling the table by having the air increased or decreased by means of a flexible hose. Air bearing pendulums are used for selectively energizing solenoid valves which either apply pressurized air to the chamber or evacuate air from the chamber by means of a vacuum source.

40 CFR 60.254 - Standards for coal processing and conveying equipment, coal storage systems, transfer and loading...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standards for coal processing and conveying equipment, coal storage systems, transfer and loading systems, and open storage piles. 60.254... (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Coal Preparation...

49 CFR 178.345-11 - Tank outlets.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Tank outlets. 178.345-11 Section 178.345-11... Containers for Motor Vehicle Transportation § 178.345-11 Tank outlets. (a) General. As used in this section, “loading/unloading outlet” means any opening in the cargo tank wall used for loading or unloading of lading...

49 CFR 178.345-11 - Tank outlets.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Tank outlets. 178.345-11 Section 178.345-11... Containers for Motor Vehicle Transportation § 178.345-11 Tank outlets. (a) General. As used in this section, “loading/unloading outlet” means any opening in the cargo tank wall used for loading or unloading of lading...

49 CFR 178.345-11 - Tank outlets.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Tank outlets. 178.345-11 Section 178.345-11... Containers for Motor Vehicle Transportation § 178.345-11 Tank outlets. (a) General. As used in this section, “loading/unloading outlet” means any opening in the cargo tank wall used for loading or unloading of lading...

49 CFR 178.345-11 - Tank outlets.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Tank outlets. 178.345-11 Section 178.345-11... Containers for Motor Vehicle Transportation § 178.345-11 Tank outlets. (a) General. As used in this section, “loading/unloading outlet” means any opening in the cargo tank wall used for loading or unloading of lading...

19 CFR 123.24 - Sealing of conveyances or compartments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... loads or lots in the same manner as less than load or compartment lots; (3) Live animals identifiable by... the expense of the parties in interest, in unsealed conveyances or compartments. (b) Seals to be affixed. The carrier shall affix blue in-transit seals to all openings of conveyances and compartments...

Evaluation and field load testing of timber railroad bridge

Treesearch

Terry J. Wipf; Michael A. Ritter; Douglas L. Wood

2000-01-01

Several spans of a 60-year-old open-deck timber railroad bridge on the Southern Pacific Railroad Line (now the Union Pacific) in Southwest Texas were field tested. The tests were conducted with the sponsorship and cooperation of the Association of American Railroads to determine the vertical live load distribution characteristics of the...

EPAct 2005: A Roadmap for Open Access

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrison, Jay A.

After nine years of negotiation characterized by significant philosophical swings, Congress came together in the middle to support a moderate vision of open access intended primarily to enable load-serving entities to obtain the transmission service they need to meet the long-term needs of their consumers reliably and economically.

High-uniformity centimeter-wide Si etching method for MEMS devices with large opening elements

NASA Astrophysics Data System (ADS)

Okamoto, Yuki; Tohyama, Yukiya; Inagaki, Shunsuke; Takiguchi, Mikio; Ono, Tomoki; Lebrasseur, Eric; Mita, Yoshio

2018-04-01

We propose a compensated mesh pattern filling method to achieve highly uniform wafer depth etching (over hundreds of microns) with a large-area opening (over centimeter). The mesh opening diameter is gradually changed between the center and the edge of a large etching area. Using such a design, the etching depth distribution depending on sidewall distance (known as the local loading effect) inversely compensates for the over-centimeter-scale etching depth distribution, known as the global or within-die(chip)-scale loading effect. Only a single DRIE with test structure patterns provides a micro-electromechanical systems (MEMS) designer with the etched depth dependence on the mesh opening size as well as on the distance from the chip edge, and the designer only has to set the opening size so as to obtain a uniform etching depth over the entire chip. This method is useful when process optimization cannot be performed, such as in the cases of using standard conditions for a foundry service and of short turn-around-time prototyping. To demonstrate, a large MEMS mirror that needed over 1 cm2 of backside etching was successfully fabricated using as-is-provided DRIE conditions.

Experimental parametric study of servers cooling management in data centers buildings

NASA Astrophysics Data System (ADS)

Nada, S. A.; Elfeky, K. E.; Attia, Ali M. A.; Alshaer, W. G.

2017-06-01

A parametric study of air flow and cooling management of data centers servers is experimentally conducted for different design conditions. A physical scale model of data center accommodating one rack of four servers was designed and constructed for testing purposes. Front and rear rack and server's temperatures distributions and supply/return heat indices (SHI/RHI) are used to evaluate data center thermal performance. Experiments were conducted to parametrically study the effects of perforated tiles opening ratio, servers power load variation and rack power density. The results showed that (1) perforated tile of 25% opening ratio provides the best results among the other opening ratios, (2) optimum benefit of cold air in servers cooling is obtained at uniformly power loading of servers (3) increasing power density decrease air re-circulation but increase air bypass and servers temperature. The present results are compared with previous experimental and CFD results and fair agreement was found.

Health monitoring of Binzhou Yellow River highway bridge using fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Ou, Jinping; Zhao, Xuefeng; Li, Hui; Zhou, Zhi; Zhang, Zhichun; Wang, Chuan

2005-05-01

Binzhou yellow river Highway Bridge with 300 meter span and 768 meter length is located in the Shandong province of China and is the first cable stayed bridge with three towers along the yellow river, one of the biggest rivers in China. In order to monitoring the strain and temperature of the bridge and evaluate the health condition, one fiber Bragg grating sensing network consists of about one hundred and thirty FBG sensors mounted in 31 monitoring sections respectively, had been built during three years time. Signal cables of sensors were led to central control room located near the main tower. One four-channel FBG interrogator was used to read the wavelengths from all the sensors, associated with four computer-controlled optic switches connected to each channel. One program was written to control the interrogator and optic switches simultaneously, and ensure signal input precisely. The progress of the monitoring can be controlled through the internet. The sensors embedded were mainly used to monitor the strain and temperature of the steel cable and reinforced concrete beam. PE jacket opening embedding technique of steel cable had been developed to embed FBG sensors safely, and ensure the reliability of the steel cable opened at the same time. Data obtained during the load test can show the strain and temperature status of elements were in good condition. The data obtained via internet since the bridge's opening to traffic shown the bridge under various load such as traffic load, wind load were in good condition.

Field Testing of Telemetry for Demand Response Control of Small Loads

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lanzisera, Steven; Weber, Adam; Liao, Anna

The electricity system in California, from generation through loads, must be prepared for high renewable penetration and increased electrification of end uses while providing increased resilience and lower operating cost. California has an aggressive renewable portfolio standard that is complemented by world-leading greenhouse gas goals. The goal of this project was to evaluate methods of enabling fast demand response (DR) signaling to small loads for low-cost site enablement. We used OpenADR 2.0 to meet telemetry requirements for providing ancillary services, and we used a variety of low-cost devices coupled with open-source software to enable an end-to-end fast DR. The devices,more » architecture, implementation, and testing of the system is discussed in this report. We demonstrate that the emerging Internet of Things (IoT) and Smart Home movements provide an opportunity for diverse small loads to provide fast, low-cost demand response. We used Internet-connected lights, thermostats, load interruption devices, and water heaters to demonstrate an ecosystem of controllable devices. The system demonstrated is capable of providing fast load shed for between 20 dollars and $300 per kilowatt (kW) of available load. The wide range results from some loads may have very low cost but also very little shed capability (a 10 watt [W] LED light can only shed a maximum of 10 W) while some loads (e.g., water heaters or air conditioners) can shed several kilowatts but have a higher initial cost. These costs, however, compare well with other fast demand response costs, with typically are over $100/kilowatt of shed. We contend these loads are even more attractive than their price suggests because many of them will be installed for energy efficiency or non-energy benefits (e.g., improved lighting quality or controllability), and the ability to use them for fast DR is a secondary benefit. Therefore the cost of enabling them for DR may approach zero if a software-only solution can be deployed to enable fast DR after devices are installed for other reasons. We recommend that the DR research community continue to engage with the IoT community to encourage the use of documented and open development interfaces. A library of device drivers and machine-readable interface specifications would significantly reduce the burden on users or system integrators for deploying systems in large numbers of buildings in California.« less

User document for computer programs for ring-stiffened shells of revolution

NASA Technical Reports Server (NTRS)

Cohen, G. A.

1973-01-01

A user manual and related program documentation is presented for six compatible computer programs for structural analysis of axisymmetric shell structures. The programs apply to a common structural model but analyze different modes of structural response. In particular, they are: (1) Linear static response under asymmetric loads; (2) Buckling of linear states under asymmetric loads; (3) Nonlinear static response under axisymmetric loads; (4) Buckling nonlinear states under axisymmetric (5) Imperfection sensitivity of buckling modes under axisymmetric loads; and (6) Vibrations about nonlinear states under axisymmetric loads. These programs treat branched shells of revolution with an arbitrary arrangement of a large number of open branches but with at most one closed branch.

Bedload and Total Load Sediment Transport Equations for Rough Open-Channel Flow

NASA Astrophysics Data System (ADS)

Abrahams, A. D.; Gao, P.

2001-12-01

The total sediment load transported by an open-channel flow may be divided into bedload and suspended load. Bedload transport occurs by saltation at low shear stress and by sheetflow at high shear stress. Dimensional analysis is used to identify the dimensionless variables that control the transport rate of noncohesive sediments over a plane bed, and regression analysis is employed to isolate the significant variables and determine the values of the coefficients. In the general bedload transport equation (i.e. for saltation and sheetflow) the dimensionless bedload transport rate is a function of the dimensionless shear stress, the friction factor, and an efficiency coefficient. For sheetflow the last term approaches 1, so that the bedload transport rate becomes a function of just the dimensionless shear stress and the friction factor. The dimensional analysis indicates that the dimensionless total load transport rate is a function of the dimensionless bedload transport rate and the dimensionless settling velocity of the sediment. Predicted values of the transport rates are graphed against the computed values of these variables for 505 flume experiments reported in the literature. These graphs indicate that the equations developed in this study give good unbiased predictions of both the bedload transport rate and total load transport rate over a wide range of conditions.

Matlab-Excel Interface for OpenDSS

DOE Office of Scientific and Technical Information (OSTI.GOV)

The software allows users of the OpenDSS grid modeling software to access their load flow models using a GUI interface developed in MATLAB. The circuit definitions are entered into a Microsoft Excel spreadsheet which makes circuit creation and editing a much simpler process than the basic text-based editors used in the native OpenDSS interface. Plot tools have been developed which can be accessed through a MATLAB GUI once the desired parameters have been simulated.

Influence of tropical seasonal variations on landfill leachate characteristics--results from lysimeter studies.

PubMed

Tränkler, J; Visvanathan, C; Kuruparan, P; Tubtimthai, O

2005-01-01

Considering the quality of design and construction of landfills in developing countries, little information can be derived from randomly taken leachate samples. Leachate generation and composition under monsoon conditions have been studied using lysimeters to simulate sanitary landfills and open cell settings. In this study, lysimeters were filled with domestic waste, highly organic market waste and pre-treated waste. Results over two subsequent dry and rainy seasons indicate that the open cell lysimeter simulation showed the highest leachate generation throughout the rainy season, with leachate flow in all lysimeters coming to a halt during the dry periods. More than 60% of the precipitation was found in the form of leachate. The specific COD and TKN load discharged from the open cell was 20% and 180% more than that of the sanitary landfill lysimeters. Types of waste material and kind of pre-treatment prior to landfilling strongly influenced the pollutant load. Compared to the sanitary landfill lysimeter filled with domestic waste, the specific COD and TKN load discharged from the pre-treated waste lysimeter accounted for only 4% and 16%, respectively. Considering the local settings of tropical landfills, these results suggest that landfill design and operation has to be adjusted. Leachate can be collected and stored during the rainy season, and recirculation of leachate is recommended to maintain a steady and even accelerated degradation during the prolonged dry season. The open cell approach in combination with leachate recirculation is suggested as an option for interim landfill operations.

14 CFR 25.365 - Pressurized compartment loads.

Code of Federal Regulations, 2011 CFR

2011-01-01

... multiplied by a factor of 1.33 for airplanes to be approved for operation to 45,000 feet or by a factor of 1.67 for airplanes to be approved for operation above 45,000 feet, omitting other loads. (e) Any... an engine disintegration; (2) Any opening in any pressurized compartment up to the size Ho in square...

Erratum: Erratum to: Effects of self-attraction and loading at a regional scale: a test case for the Northwest European Shelf

NASA Astrophysics Data System (ADS)

Irazoqui Apecechea, Maialen; Verlaan, Martin; Zijl, Firmijn; Le Coz, Camille; Kernkamp, Herman

2017-12-01

The article Effects of self-attraction and loading at a regional scale: a test case for the Northwest European Shelf, written by Maialen Irazoqui Apecechea, Martin Verlaan, Firmijn Zijl, Camille Le Coz and Herman Kernkamp, was originally published Online First without open access.

40 CFR 86.884-7 - Dynamometer operation cycle for smoke emission tests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... provide the speed and load necessary to comply with the heavy-duty “curb idle” definition per § 86.084-2..., and held in, the fully open position. The inertia of the engine and the dynamometer, or alternately a... mode, motoring assist may be used to offset excessive dynamometer inertia load when necessary. No...

40 CFR 86.884-7 - Dynamometer operation cycle for smoke emission tests.

Code of Federal Regulations, 2012 CFR

2012-07-01

... be set to provide the speed and load necessary to comply with the heavy-duty “curb idle” definition..., and held in, the fully open position. The inertia of the engine and the dynamometer, or alternately a... mode, motoring assist may be used to offset excessive dynamometer inertia load when necessary. No...

40 CFR 86.884-7 - Dynamometer operation cycle for smoke emission tests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... be set to provide the speed and load necessary to comply with the heavy-duty “curb idle” definition..., and held in, the fully open position. The inertia of the engine and the dynamometer, or alternately a... mode, motoring assist may be used to offset excessive dynamometer inertia load when necessary. No...

40 CFR 86.884-7 - Dynamometer operation cycle for smoke emission tests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... be set to provide the speed and load necessary to comply with the heavy-duty “curb idle” definition..., and held in, the fully open position. The inertia of the engine and the dynamometer, or alternately a... mode, motoring assist may be used to offset excessive dynamometer inertia load when necessary. No...

Employing Nested OpenMP for the Parallelization of Multi-Zone Computational Fluid Dynamics Applications

NASA Technical Reports Server (NTRS)

Ayguade, Eduard; Gonzalez, Marc; Martorell, Xavier; Jost, Gabriele

2004-01-01

In this paper we describe the parallelization of the multi-zone code versions of the NAS Parallel Benchmarks employing multi-level OpenMP parallelism. For our study we use the NanosCompiler, which supports nesting of OpenMP directives and provides clauses to control the grouping of threads, load balancing, and synchronization. We report the benchmark results, compare the timings with those of different hybrid parallelization paradigms and discuss OpenMP implementation issues which effect the performance of multi-level parallel applications.

46 CFR 160.043-5 - Inspections and tests.

Code of Federal Regulations, 2010 CFR

2010-10-01

... rectangular and circular cans, and shall show no noticeable loss in cutting ability. ... position, a downward load of 15 pounds shall be suspended from the lanyard and allowed to hang for a period... the blade and the can opener shall open and close properly, and the knife shall show no other evidence...

46 CFR 160.043-5 - Inspections and tests.

Code of Federal Regulations, 2013 CFR

2013-10-01

... rectangular and circular cans, and shall show no noticeable loss in cutting ability. ... position, a downward load of 15 pounds shall be suspended from the lanyard and allowed to hang for a period... the blade and the can opener shall open and close properly, and the knife shall show no other evidence...

46 CFR 160.043-5 - Inspections and tests.

Code of Federal Regulations, 2012 CFR

2012-10-01

... rectangular and circular cans, and shall show no noticeable loss in cutting ability. ... position, a downward load of 15 pounds shall be suspended from the lanyard and allowed to hang for a period... the blade and the can opener shall open and close properly, and the knife shall show no other evidence...

46 CFR 160.043-5 - Inspections and tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

... rectangular and circular cans, and shall show no noticeable loss in cutting ability. ... position, a downward load of 15 pounds shall be suspended from the lanyard and allowed to hang for a period... the blade and the can opener shall open and close properly, and the knife shall show no other evidence...

46 CFR 160.043-5 - Inspections and tests.

Code of Federal Regulations, 2014 CFR

2014-10-01

... rectangular and circular cans, and shall show no noticeable loss in cutting ability. ... position, a downward load of 15 pounds shall be suspended from the lanyard and allowed to hang for a period... the blade and the can opener shall open and close properly, and the knife shall show no other evidence...

14 CFR Appendix - Special Federal Aviation Regulation No. 109

Code of Federal Regulations, 2011 CFR

2011-01-01

... absorbing protective padding (foam or equivalent) such as Ensolite. (6) Shoulder Strap Loads. Where upper... must have a means to signal to the flightcrew, at the flightdeck, that the door is in the open position... that any such door is in the open configuration for takeoff and landing. (c) Each door between any...

14 CFR Appendix - Special Federal Aviation Regulation No. 109

Code of Federal Regulations, 2012 CFR

2012-01-01

... absorbing protective padding (foam or equivalent) such as Ensolite. (6) Shoulder Strap Loads. Where upper... must have a means to signal to the flightcrew, at the flightdeck, that the door is in the open position... that any such door is in the open configuration for takeoff and landing. (c) Each door between any...

14 CFR Appendix - Special Federal Aviation Regulation No. 109

Code of Federal Regulations, 2013 CFR

2013-01-01

... absorbing protective padding (foam or equivalent) such as Ensolite. (6) Shoulder Strap Loads. Where upper... must have a means to signal to the flightcrew, at the flightdeck, that the door is in the open position... that any such door is in the open configuration for takeoff and landing. (c) Each door between any...

14 CFR Appendix - Special Federal Aviation Regulation No. 109

Code of Federal Regulations, 2014 CFR

2014-01-01

... absorbing protective padding (foam or equivalent) such as Ensolite. (6) Shoulder Strap Loads. Where upper... must have a means to signal to the flightcrew, at the flightdeck, that the door is in the open position... that any such door is in the open configuration for takeoff and landing. (c) Each door between any...

Improving Open Access through Prior Learning Assessment

ERIC Educational Resources Information Center

Yin, Shuangxu; Kawachi, Paul

2013-01-01

This paper explores and presents new data on how to improve open access in distance education through using prior learning assessments. Broadly there are three types of prior learning assessment (PLAR): Type-1 for prospective students to be allowed to register for a course; Type-2 for current students to avoid duplicating work-load to gain…

22 CFR 89.1 - Prohibitions on Longshore work by U.S. nationals; listing by country.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of sophisticated cargo-related equipment on container vessels, (2) First opening and last closing of... respect to the particular activities noted: Albania (a) Cargo loading and discharge. (b) Exceptions: (1) Operation of cargo related equipment, (2) Opening and closing of hatches, and (3) Rigging of ship's gear...

22 CFR 89.1 - Prohibitions on Longshore work by U.S. nationals; listing by country.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of sophisticated cargo-related equipment on container vessels, (2) First opening and last closing of... respect to the particular activities noted: Albania (a) Cargo loading and discharge. (b) Exceptions: (1) Operation of cargo related equipment, (2) Opening and closing of hatches, and (3) Rigging of ship's gear...

22 CFR 89.1 - Prohibitions on Longshore work by U.S. nationals; listing by country.

Code of Federal Regulations, 2014 CFR

2014-04-01

... of sophisticated cargo-related equipment on container vessels, (2) First opening and last closing of... respect to the particular activities noted: Albania (a) Cargo loading and discharge. (b) Exceptions: (1) Operation of cargo related equipment, (2) Opening and closing of hatches, and (3) Rigging of ship's gear...

22 CFR 89.1 - Prohibitions on Longshore work by U.S. nationals; listing by country.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of sophisticated cargo-related equipment on container vessels, (2) First opening and last closing of... respect to the particular activities noted: Albania (a) Cargo loading and discharge. (b) Exceptions: (1) Operation of cargo related equipment, (2) Opening and closing of hatches, and (3) Rigging of ship's gear...

Reliability analysis for determining performance of barrage based on gates operation

NASA Astrophysics Data System (ADS)

Adiningrum, C.; Hadihardaja, I. K.

2017-06-01

Some rivers located on a flat slope topography such as Cilemahabang river and Ciherang river in Cilemahabang watershed, Bekasi regency, West Java are susceptible to flooding. The inundation mostly happens near a barrage in the middle and downstream of the Cilemahabang watershed, namely the Cilemahabang and Caringin barrages. Barrages or gated weirs are difficult to exploit since the gate must be kept and operated properly under any circumstances. Therefore, a reliability analysis of the gates operation is necessary to determine the performance of the barrage with respect to the number of gates opened and the gates opening heights. The First Order Second Moment (FOSM) method was used to determine the performance by the reliability index (β) and the probability of failure (risk). It was found that for Cilemahabang Barrage, the number of gates opened with load (L) represents the peak discharge derived from various rainfall (P) respectively one gate with opening height (h=1m) for Preal, two gates (h=1m and h=1,5m) for P50, and three gates (each gate with h=2,5m) for P100. For Caringin Barrage, the results are minimum three gates opened (each gate with h=2,5 m) for Preal, five gates opened (each gate with h=2,5m) for P50, and six gates opened (each gate with h=2,5m) for P100. It can be concluded that a greater load (L) needs greater resistance (R) to counterbalance. Resistance can be added by increasing the number of gates opened and the gate opening height. A higher number of gates opened will lead to the decrease of water level in the upstream of barrage and less risk of overflow.

Microcracking and Healing in Semibrittle Salt-Rock: Elastic and Plastic Behavior

NASA Astrophysics Data System (ADS)

Ding, J.; Chester, F. M.; Chester, J. S.; Shen, X.; Arson, C. F.

2017-12-01

Microcracking and healing during semibrittle deformation are important processes that affect physical properties such as elastic moduli and permeability. We study these processes through triaxial compression tests involving cyclic differential loading and isostatic-holds on synthetic salt-rock at room temperature and low confining pressure (Pc, 1 to 4 MPa). The salt samples are produced by uniaxial pressing of granular (300 µm dia.) halite to 75 MPa at 150˚C for 10^3 s, to create low-porosity ( 5%) aggregates of nearly equant, work-hardened grains. Alternating large- and small-load cycles are performed to track the evolution of plastic and elastic properties, respecitively, with progressive strain to 8% axial shortening. 24-hour holds are carried out at about 4% axial shortening followed by renewed cyclic loading to investigate healing. During large load cycles samples yield and exhibit distributed flow with dilatancy and small work hardening. Young's Modulus (YM) decreases and then tends to stabilize, while Poisson's Ratio (PR) increases at a reducing rate, with progressive strain. Microstructures at sequential stages show that opening-mode grain-boundary cracking, grain-boundary sliding, and some intracrystalline plasticity are the dominant deformation processes. Opening and shear occur preferentially on boundaries that are parallel and inclined to the shortening axis, respectively, leading to progressive redistribution of porosity. Opening-mode grain-boundary cracks increase in number and aperature with strain, and are linked by sliding grain-boundaries to form en echelon arrays. After a 24-hour hold, samples show yielding and flow behavior consistent with that prior to the hold, whereas YM and PR are reset to the same values documented at zero strain and subsequently evolve with additional strain similar to that documented at smaller strains prior to the hold. Open grain-boundary cracks are not closed or healed during the hold. Observations suggest that changes in elastic properties in the semibrittle salt-rock reflect weakening and healing of grain-boundaries undergoing sliding rather than progressive dilatancy or healing of opening-mode cracks. Findings are being used to inform and develop continuum damage mechanics models of semibrittle deformation in polycrystalline aggregates

Factors affecting the open-circuit voltage and electrode kinetics of some iron/titanium/redox flow cells

NASA Technical Reports Server (NTRS)

Reid, M. A.; Gahn, R. F.

1977-01-01

The effect of acid concentration on the performance of the iron-titanium redox flow cell was studied. When the acidity was increased, open-circuit voltages decreased on the titanium side but load voltages increased due to decreased polarization. The best load voltage occurs when there is high acidity on the titanium side coupled with low acidity on the iron side, but such cells show voltage losses with repeated cycling because of the diffusion of acid through the membrane. No membrane tested has been found capable of maintaining the differences in acidity. Chelating agents show some promise in reducing polarization at the Ti electrode and thus improving energy efficiency.

Variability of normal vocal fold dynamics for different vocal loading in one healthy subject investigated by phonovibrograms.

PubMed

Doellinger, Michael; Lohscheller, Joerg; McWhorter, Andrew; Kunduk, Melda

2009-03-01

We investigate the potential of high-speed digital imaging technique (HSI) and the phonovibrogram (PVG) analysis in normal vocal fold dynamics by studying the effects of continuous voice use (vocal loading) during the workday. One healthy subject was recorded at sustained phonation 13 times within 2 consecutive days in the morning before and in the afternoon after vocal loading, respectively. Vocal fold dynamics were extracted and visualized by PVGs. The characteristic PVG patterns were extracted representing vocal fold vibration types. The parameter values were then analyzed by statistics regarding vocal load, left-right PVG asymmetries, anterior-posterior PVG asymmetries, and opening-closing differences. For the first time, the direct impact of vocal load could be determined by analyzing vocal fold dynamics. For same vocal loading conditions, equal dynamical behavior of the vocal folds were confirmed. Comparison of recordings performed in the morning with the recordings after work revealed significant changes in vibration behavior, indicating impact of occurring vocal load. Left-right asymmetries in vocal fold dynamics were found confirming earlier assumptions. Different dynamics between opening and closing procedure as well as for anterior and posterior parts were found. Constant voice usage stresses the vocal folds even in healthy subjects and can be detected by applying the PVG technique. Furthermore, left-right PVG asymmetries do occur in healthy voice to a certain extent. HSI in combination with PVG analysis seems to be a promising tool for investigation of vocal fold fatigue and pathologies resulting in small forms of dynamical changes.

Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model.

PubMed

Ter Boo, Gert-Jan A; Arens, Daniel; Metsemakers, Willem-Jan; Zeiter, Stephan; Richards, R Geoff; Grijpma, Dirk W; Eglin, David; Moriarty, T Fintan

2016-10-01

Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis. Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel thermo-responsive hyaluronan based hydrogel with control over gelation temperature is reported. The efficacy of this gentamicin loaded hyaluronan derivative is demonstrated in an in vivo fracture model in the presence of fracture fixation hardware. The bacterial burden is cleared in all of the inoculated rabbits in the presence of the ALB. Thus, the proposed injectable thermo-responsive hyaluronan presents an effective ALB for the prevention of infection. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Structure of energy consumption and improving open-pit dump truck efficiency

NASA Astrophysics Data System (ADS)

Koptev, V. Yu; Kopteva, A. V.

2017-10-01

This paper studies the dynamics of the improvement of wheel type transport vehicles environmental and energy performance in open-pit mines. The paper discloses characteristics of the gas turbine engine with capacity of 1250 hp, mounted on tanks, and technical-economic calculations, confirming reasonability of their use in open-pit dump trucks with the 120 …130-ton loading capacity. The general layout scheme of mechanical transmission with the gas turbine engine is shown.

Opportunities for Energy Efficiency and Open Automated Demand Response in Wastewater Treatment Facilities in California -- Phase I Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lekov, Alex; Thompson, Lisa; McKane, Aimee

This report summarizes the Lawrence Berkeley National Laboratory?s research to date in characterizing energy efficiency and automated demand response opportunities for wastewater treatment facilities in California. The report describes the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy use and demand, as well as details of the wastewater treatment process. It also discusses control systems and energy efficiency and automated demand response opportunities. In addition, several energy efficiency and load management case studies are provided for wastewater treatment facilities.This study shows that wastewater treatment facilities can be excellent candidates for open automated demand response and thatmore » facilities which have implemented energy efficiency measures and have centralized control systems are well-suited to shift or shed electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. Control technologies installed for energy efficiency and load management purposes can often be adapted for automated demand response at little additional cost. These improved controls may prepare facilities to be more receptive to open automated demand response due to both increased confidence in the opportunities for controlling energy cost/use and access to the real-time data.« less

An Experimental Study of a Stitched Composite with a Notch Subjected to Combined Bending and Tension Loading

NASA Technical Reports Server (NTRS)

Palmer, Susan O.; Nettles, Alan T.; Poe, C. C., Jr.

1999-01-01

A series of tests was conducted to measure the strength of stitched carbon/epoxy composites containing through-thickness damage in the form of a crack-like notch. The specimens were subjected to three types of loading: pure bending, pure tension, and combined bending and tension loads. Measurements of applied loads, strains near crack tips, and crack opening displacements (COD) were monitored in all tests. The transverse displacement at the center of the specimen was measured using a Linear Variable Differential Transformer (LVDT). The experimental data showed that the outer surface of the pure tension specimen failed at approximately 6,000 microstrain, while in combined bending and tension loads the measured tensile strains reached 10,000 microstrain.

Load Asymmetry Observed During Orion Main Parachute Inflation

NASA Technical Reports Server (NTRS)

Morris, Aaron L.; Taylor, Thomas; Olson, Leah

2011-01-01

The Crew Exploration Vehicle Parachute Assembly System (CPAS) has flight tested the first two generations of the Orion parachute program. Three of the second generation tests instrumented the dispersion bridles of the Main parachute with a Tension Measuring System. The goal of this load measurement was to better understand load asymmetry during the inflation process of a cluster of Main parachutes. The CPAS Main parachutes exhibit inflations that are much less symmetric than current parachute literature and design guides would indicate. This paper will examine loads data gathered on three cluster tests, quantify the degree of asymmetry observed, and contrast the results with published design guides. Additionally, the measured loads data will be correlated with videos of the parachute inflation to make inferences about the shape of the parachute and the relative load asymmetry. The goal of this inquiry and test program is to open a dialogue regarding asymmetrical parachute inflation load factors.

29 CFR Appendix E to Subpart M of... - Sample Fall Protection Plan

Code of Federal Regulations, 2012 CFR

2012-07-01

... system shall not be used when the wind is strong enough to cause loads with large surface areas to swing out of radius, or result in loss of control of the load, or when weather conditions cause the walking... column is through the slab opening, there will no longer exist a fall hazard at this location. III...

29 CFR Appendix E to Subpart M of... - Sample Fall Protection Plan

Code of Federal Regulations, 2013 CFR

2013-07-01

... system shall not be used when the wind is strong enough to cause loads with large surface areas to swing out of radius, or result in loss of control of the load, or when weather conditions cause the walking... column is through the slab opening, there will no longer exist a fall hazard at this location. III...

29 CFR Appendix E to Subpart M of... - Sample Fall Protection Plan

Code of Federal Regulations, 2011 CFR

2011-07-01

... system shall not be used when the wind is strong enough to cause loads with large surface areas to swing out of radius, or result in loss of control of the load, or when weather conditions cause the walking... column is through the slab opening, there will no longer exist a fall hazard at this location. III...

Influence of upstream disturbance on the draft-tube flow of Francis turbine under part-load conditions

NASA Astrophysics Data System (ADS)

Chen, Ting; Zheng, Xianghao; Zhang, Yu-ning; Li, Shengcai

2018-02-01

Owing to the part-load operations for the enhancement of grid flexibility, the Francis turbine often suffers from severe low-frequency and large-amplitude hydraulic instability, which is mostly pertinent to the highly unsteady swirling vortex rope in the draft tube. The influence of disturbances in the upstream (e.g., large-scale vortex structures in the spiral casing) on the draft-tube vortex flow is not well understood yet. In the present paper, the influence of the upstream disturbances on the vortical flow in the draft tube is studied based on the vortex identification method and the analysis of several important parameters (e.g., the swirl number and the velocity profile). For a small guide vane opening (representing the part-load condition), the vortices triggered in the spiral casing propagate downstream and significantly affect the swirling vortex-rope precession in the draft tube, leading to the changes of the intensity and the processional frequency of the swirling vortex rope. When the guide vane opening approaches the optimum one (representing the full-load condition), the upstream disturbance becomes weaker and thus its influences on the downstream flow are very limited.

Sensitivity and specificity of eustachian tube function tests in adults.

PubMed

Doyle, William J; Swarts, J Douglas; Banks, Julianne; Casselbrant, Margaretha L; Mandel, Ellen M; Alper, Cuneyt M

2013-07-01

The study demonstrates the utility of eustachian tube (ET) function (ETF) test results for accurately assigning ears to disease state. To determine if ETF tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and to define the interrelatedness of ETF test parameters. Through use of the forced-response, inflation-deflation, Valsalva, and sniffing tests, ETF was evaluated in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). Data were analyzed using logistic regression including each parameter independently and then a step-down discriminant analysis including all ETF test parameters to predict group assignment. Factor analysis operating over all parameters was used to explore relatedness. ETF testing. ETF parameters for the forced response, inflation-deflation, Valsalva, and sniffing tests measured in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). The discriminant analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency, and percentage of positive pressure equilibrated) that together correctly assigned ears to group 2 at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters: the first had negative loadings of the ETF structural parameters; the second had positive loadings of the muscle-assisted ET opening parameters; and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters. These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories.

Modeling Force Transfer around Openings in Wood-Frame Shear Walls

Treesearch

Minghao Li; Frank Lam; Borjen Yeh; Tom Skaggs; Doug Rammer; James Wacker

2012-01-01

This paper presented a modeling study on force transfer around openings (FTAO) in wood-frame shear walls detailed for FTAO. To understand the load transfer in the walls, this study used a finite-element model WALL2D, which is able to model individual wall components, including framing members, sheathing panels, oriented panel-frame nailed connections, framing...

Lightweight Monorail Transport System

NASA Technical Reports Server (NTRS)

Weir, Harold F.; Wood, Kenneth E.; Strecker, Myron T.

1987-01-01

Report proposes monorail transportation system for zero-gravity environment. System carries materials and parts between locations on space station. Includes tubular rails instead of open channels usually found in overhead conveyor systems. Since resistance to torque of closed tube greater than that of open channel for same amount of material, tubular monorail designed for higher loads or for greater spacing between support points.

A High Power Solid State Circuit Breaker for Military Hybrid Electric Vehicle Applications

DTIC Science & Technology

2012-08-01

the SSCB to isolate a fault, breaker opening is latched and can be reset to reclose the breaker via remote logic input. SSCB state and health...rated load current (125 A). Figure 10 shows that after the SSCB detects a fault and opens, it can also be repeatedly reclosed remotely to attempt to

Earthquake response of heavily damaged historical masonry mosques after restoration

NASA Astrophysics Data System (ADS)

Altunışık, Ahmet Can; Fuat Genç, Ali

2017-10-01

Restoration works have been accelerated substantially in Turkey in the last decade. Many historical buildings, mosques, minaret, bridges, towers and structures have been restored. With these restorations an important issue arises, namely how restoration work affects the structure. For this reason, we aimed to investigate the restoration effect on the earthquake response of a historical masonry mosque considering the openings on the masonry dome. For this purpose, we used the Hüsrev Pasha Mosque, which is located in the Ortakapı district in the old city of Van, Turkey. The region of Van is in an active seismic zone; therefore, earthquake analyses were performed in this study. Firstly a finite element model of the mosque was constructed considering the restoration drawings and 16 window openings on the dome. Then model was constructed with eight window openings. Structural analyses were performed under dead load and earthquake load, and the mode superposition method was used in analyses. Maximum displacements, maximum-minimum principal stresses and shear stresses are given with contours diagrams. The results are analyzed according to Turkish Earthquake Code (TEC, 2007) and compared between 8 and 16 window openings cases. The results show that reduction of the window openings affected the structural behavior of the mosque positively.

Nutrient loading and macrophyte growth in Wilson Inlet, a bar-built southwestern Australian estuary

NASA Astrophysics Data System (ADS)

Lukatelich, R. J.; Schofield, N. J.; McComb, A. J.

1987-02-01

Wilson Inlet is a 'bar-built' estuary, open to the ocean only when a sandbar has been breached after river flow. estimates are presented of phosphorus and nitrogen loadings from rivers, losses to the ocean, and amounts present in estuarine components during a particular year. Following bar opening, a volume of water equivalent to 35% of estuarine volume at the time was lost, providing a major loss of dissolved nutrients from the estuary. While the bar was open (51 days) water was displaced through river flow, but there was little tidal exchange. There was net retention of phosphorus (about 60% of river input) and some loss of nitrogen (less than 15%). Much of the nutrient held in the estuary was in surface sediments, but concentrations have shown little change with time and are similar to other southwestern estuaries. In contrast there have been massive increases in the biomass of Ruppia megacarpa Mason in recent years; this constitutes more than 90% of plant biomass. The nutrient bank in this plant is large compared to the water column, and amounts recycled through plant material greatly exceeded riverine loading in the year of the study. Tissue N concentrations were relatively high and constant, tissue P relatively low and seasonally variable, suggesting P limitation of plant biomass. Estimates of nutrient loading from streams showed relatively higher nutrient inputs from catchments cleared for agriculture. These are in higher rainfall areas, have high drainage densities, large proportions of sandy soils and are subjected to phosphatic fertilizer application.

Bright x-rays reveal shifting deformation states and effects of the microstructure on the plastic deformation of crystalline materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beaudoin, A. J.; Shade, P. A.; Schuren, J. C.

The plastic deformation of crystalline materials is usually modeled as smoothly progressing in space and time, yet modern studies show intermittency in the deformation dynamics of single-crystals arising from avalanche behavior of dislocation ensembles under uniform applied loads. However, once the prism of the microstructure in polycrystalline materials disperses and redistributes the load on a grain-by-grain basis, additional length and time scales are involved. Thus, the question is open as to how deformation intermittency manifests for the nonuniform grain-scale internal driving forces interacting with the finer-scale dislocation ensemble behavior. In this work we track the evolution of elastic strain withinmore » individual grains of a creep-loaded titanium alloy, revealing widely varying internal strains that fluctuate over time. Here, the findings provide direct evidence of how flow intermittency proceeds for an aggregate of ~700 grains while showing the influences of multiscale ensemble interactions and opening new avenues for advancing plasticity modeling.« less

Bright x-rays reveal shifting deformation states and effects of the microstructure on the plastic deformation of crystalline materials

DOE PAGES

Beaudoin, A. J.; Shade, P. A.; Schuren, J. C.; ...

2017-11-30

The plastic deformation of crystalline materials is usually modeled as smoothly progressing in space and time, yet modern studies show intermittency in the deformation dynamics of single-crystals arising from avalanche behavior of dislocation ensembles under uniform applied loads. However, once the prism of the microstructure in polycrystalline materials disperses and redistributes the load on a grain-by-grain basis, additional length and time scales are involved. Thus, the question is open as to how deformation intermittency manifests for the nonuniform grain-scale internal driving forces interacting with the finer-scale dislocation ensemble behavior. In this work we track the evolution of elastic strain withinmore » individual grains of a creep-loaded titanium alloy, revealing widely varying internal strains that fluctuate over time. Here, the findings provide direct evidence of how flow intermittency proceeds for an aggregate of ~700 grains while showing the influences of multiscale ensemble interactions and opening new avenues for advancing plasticity modeling.« less

A versatile electrostatic trap with open optical access

NASA Astrophysics Data System (ADS)

Li, Sheng-Qiang; Yin, Jian-Ping

2018-04-01

A versatile electrostatic trap with open optical access for cold polar molecules in weak-field-seeking state is proposed in this paper. The trap is composed of a pair of disk electrodes and a hexapole. With the help of a finite element software, the spatial distribution of the electrostatic field is calculated. The results indicate that a three-dimensional closed electrostatic trap is formed. Taking ND3 molecules as an example, the dynamic process of loading and trapping is simulated. The results show that when the velocity of the molecular beam is 10 m/s and the loading time is 0.9964 ms, the maximum loading efficiency reaches 94.25% and the temperature of the trapped molecules reaches about 30.3 mK. A single well can be split into two wells, which is of significant importance to the precision measurement and interference of matter waves. This scheme, in addition, can be further miniaturized to construct one-dimensional, two-dimensional, and three-dimensional spatial electrostatic lattices.

John F. Kennedy Space Center's Wireless Hang Angle Instrumentation System

NASA Technical Reports Server (NTRS)

Kohler, Jeff

2009-01-01

The technology is a high-precision, wireless inclinometer. The system was designed for monitoring the suspension angle of the Orbiter vehicle during loading onto the Solid Rocket Boosters of the Space Shuttle. Originally, operators manually measured the alignment of the Orbiter with a hand-held inclinometer on a nonrigid surface. The measurement was open to interpretation by the loader. If the Orbiter is misaligned, it can crush ball joints and delay the loading while repairs are made. With this system, the Orbiter can be loaded without damage and without manual measurement.

The Dugdale model for the compact specimen

NASA Technical Reports Server (NTRS)

Mall, S.; Newman, J. C., Jr.

1983-01-01

Plastic zone size and crack tip opening displacement (CTOD) equations were developed. Boundary collocation analyses were used to analyze the compact specimen subjected to various loading conditions (pin loads, concentrated forces, and uniform pressure acting on the crack surface). Stress intensity factor and crack surface displacement equations for some of these loadings were developed and used to obtain the Dugdale model. The results from the equations for plastic zone size and CTOD agreed well with numerical values calculated by Terada for crack length to width ratios greater than 0.4.

Estimation of lumbar spinal loading and trunk muscle forces during asymmetric lifting tasks: application of whole-body musculoskeletal modelling in OpenSim.

PubMed

Kim, Hyun-Kyung; Zhang, Yanxin

2017-04-01

Large spinal compressive force combined with axial torsional shear force during asymmetric lifting tasks is highly associated with lower back injury (LBI). The aim of this study was to estimate lumbar spinal loading and muscle forces during symmetric lifting (SL) and asymmetric lifting (AL) tasks using a whole-body musculoskeletal modelling approach. Thirteen healthy males lifted loads of 7 and 12 kg under two lifting conditions (SL and AL). Kinematic data and ground reaction force data were collected and then processed by a whole-body musculoskeletal model. The results show AL produced a significantly higher peak lateral shear force as well as greater peak force of psoas major, quadratus lumborum, multifidus, iliocostalis lumborum pars lumborum, longissimus thoracis pars lumborum and external oblique than SL. The greater lateral shear forces combined with higher muscle force and asymmetrical muscle contractions may have the biomechanical mechanism responsible for the increased risk of LBI during AL. Practitioner Summary: Estimating lumbar spinal loading and muscle forces during free-dynamic asymmetric lifting tasks with a whole-body musculoskeletal modelling in OpenSim is the core value of this research. The results show that certain muscle groups are fundamentally responsible for asymmetric movement, thereby producing high lumbar spinal loading and muscle forces, which may increase risks of LBI during asymmetric lifting tasks.

The effect of knee extensor open kinetic chain resistance training in the ACL-injured knee.

PubMed

Barcellona, Massimo G; Morrissey, Matthew C; Milligan, Peter; Clinton, Melissa; Amis, Andrew A

2015-11-01

To investigate the effect of different loads of knee extensor open kinetic chain resistance training on anterior knee laxity and function in the ACL-injured (ACLI) knee. Fifty-eight ACLI subjects were randomised to one of three (12-week duration) training groups. The STAND group trained according to a standardised rehabilitation protocol. Subjects in the LOW and HIGH group trained as did the STAND group but with the addition of seated knee extensor open kinetic chain resistance training at loads of 2 sets of 20 repetition maximum (RM) and 20 sets of 2RM, respectively. Anterior knee laxity and measurements of physical and subjective function were performed at baseline, 6 and 12 weeks. Thirty-six subjects were tested at both baseline and 12 weeks (STAND n = 13, LOW n = 11, HIGH n = 12). The LOW group demonstrated a reduction in 133 N anterior knee laxity between baseline and 12 weeks testing when compared to the HIGH and the STAND groups (p = 0.009). Specifically, the trained-untrained knee laxity decreased an average of approximately 5 mm in the LOW group while remaining the same in the other two groups. Twelve weeks of knee extensor open kinetic chain resistance training at loads of 2 sets of 20RM led to a reduction in anterior knee laxity in the ACLI knee. This reduction in laxity does not appear to offer any significant short-term functional advantages when compared to a standard rehabilitation protocol. These results indicate that knee laxity can be decreased with resistance training of the thigh muscles. Randomised controlled trial, Level II.

Linoleic Acid Permeabilizes Gastric Epithelial Cells by Increasing Connexin43 Levels in the Cell Membrane Via a GPR40- and Akt-Dependent Mechanism

PubMed Central

Puebla, Carlos; Cisterna, Bruno A.; Salas, Daniela P.; Delgado-López, Fernando; Lampe, Paul D.; Sáez, Juan C.

2016-01-01

Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors. The Cx HC activity of these cells increased after 5 min of treatment with LA or GW9508, an agonist of GPR40/GPR120; or exposure to extracellular divalent cation-free solution (DCFS), known to increase the open probability of Cx HCs, yields an immediate increase in Cx HC of similar intensity and additive with LA-induced change. Treatment with a CD36 blocker or transfection with siRNA-GPR120 maintain the LA-induced Cx HC activity. However, cells transfected with siRNA-GPR40 did not show LA-induced Cx HC activity but activity was increased upon exposure to DCFS, confirming the presence of activatable Cx HCs in the cell membrane. Treatment with AKTi (Akt inhibitor) abrogated the LA-induced Cx HC activity. In HeLa cells transfected with Cx43 (HeLa-Cx43), LA induced phosphorylation of surface Cx43 at serine 373 (S373), site for Akt phosphorylation. HeLa-Cx43 but not HeLa-Cx43 cells with a S373A mutation showed a LA-induced Cx HC activity directly related to an increase in cell surface Cx43 levels. Thus, the increase in membrane permeability induced by LA is mediated by an intracellular signaling pathway activated by GPR40 that leads to an increase in membrane levels of Cx43 phosphorylated at serine 373 via Akt. PMID:26869446

Methamphetamine compromises gap junctional communication in astrocytes and neurons.

PubMed

Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R; Eugenin, Eliseo A

2016-05-01

Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. Methamphetamine (meth) is an extremely addictive central nervous system stimulant. Meth reduced gap junctional (GJ) communication by inducing internalization of connexin-43 (Cx43) in astrocytes and reducing expression of Cx36 in neurons by a mechanism involving activation of dopamine receptors (see cartoon). Meth-induced changes in Cx containing channels increased extracellular levels of glutamate and resulted in higher sensitivity of neurons and astrocytes to apoptosis in response to HIV infection. © 2016 International Society for Neurochemistry.

Field Experience with Lock Culvert Valves

DTIC Science & Technology

2013-12-01

factors pertaining to valves such as the hoist loads, cavitation parameter, and effects of venting. To reduce the surge in the navigation channel...2 min 15 sec, filling-and-emptying valve opening time) ensures that adequate air is drawn into the culvert to cushion the cavitation implosions...shape can have adverse hydrodynamic loading consequences. The USACE, Mobile District (SAM) is in the process of designing replacement valves that are

Analysis and Design of Connections, Openings and Attachments for Protective Construction

DTIC Science & Technology

1989-10-01

precast connection details were subjected to cyclic simulated earthquake loads . The detail... column and beam flexural steel. At the onset of flexural yield under cyclical loading , crack sizes at the face of the joint increase and reinforcement... beam / column connections may be a necessity and can be placed without a great deal of difficulty. However, their placement in slab/wall connections

Measuring Cognitive Load with Subjective Rating Scales during Problem Solving: Differences between Immediate and Delayed Ratings

ERIC Educational Resources Information Center

Schmeck, Annett; Opfermann, Maria; van Gog, Tamara; Paas, Fred; Leutner, Detlev

2015-01-01

Subjective cognitive load (CL) rating scales are widely used in educational research. However, there are still some open questions regarding the point of time at which such scales should be applied. Whereas some studies apply rating scales directly after each step or task and use an average of these ratings, others assess CL only once after the…

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2012 CFR

2012-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2014 CFR

2014-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2013 CFR

2013-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2011 CFR

2011-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2010 CFR

2010-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

Perceptual Load Affects Eyewitness Accuracy and Susceptibility to Leading Questions.

PubMed

Murphy, Gillian; Greene, Ciara M

2016-01-01

Load Theory (Lavie, 1995, 2005) states that the level of perceptual load in a task (i.e., the amount of information involved in processing task-relevant stimuli) determines the efficiency of selective attention. There is evidence that perceptual load affects distractor processing, with increased inattentional blindness under high load. Given that high load can result in individuals failing to report seeing obvious objects, it is conceivable that load may also impair memory for the scene. The current study is the first to assess the effect of perceptual load on eyewitness memory. Across three experiments (two video-based and one in a driving simulator), the effect of perceptual load on eyewitness memory was assessed. The results showed that eyewitnesses were less accurate under high load, in particular for peripheral details. For example, memory for the central character in the video was not affected by load but memory for a witness who passed by the window at the edge of the scene was significantly worse under high load. High load memories were also more open to suggestion, showing increased susceptibility to leading questions. High visual perceptual load also affected recall for auditory information, illustrating a possible cross-modal perceptual load effect on memory accuracy. These results have implications for eyewitness memory researchers and forensic professionals.

Perceptual Load Affects Eyewitness Accuracy and Susceptibility to Leading Questions

PubMed Central

Murphy, Gillian; Greene, Ciara M.

2016-01-01

Load Theory (Lavie, 1995, 2005) states that the level of perceptual load in a task (i.e., the amount of information involved in processing task-relevant stimuli) determines the efficiency of selective attention. There is evidence that perceptual load affects distractor processing, with increased inattentional blindness under high load. Given that high load can result in individuals failing to report seeing obvious objects, it is conceivable that load may also impair memory for the scene. The current study is the first to assess the effect of perceptual load on eyewitness memory. Across three experiments (two video-based and one in a driving simulator), the effect of perceptual load on eyewitness memory was assessed. The results showed that eyewitnesses were less accurate under high load, in particular for peripheral details. For example, memory for the central character in the video was not affected by load but memory for a witness who passed by the window at the edge of the scene was significantly worse under high load. High load memories were also more open to suggestion, showing increased susceptibility to leading questions. High visual perceptual load also affected recall for auditory information, illustrating a possible cross-modal perceptual load effect on memory accuracy. These results have implications for eyewitness memory researchers and forensic professionals. PMID:27625628

The Power of a Soccer Ball: A Traumatic Open Finger Dislocation-A Rare Case Presentation.

PubMed

Dülgeroğlu, Turan Cihan; Metineren, Hasan; Aydın, Ekrem; Dülgeroğlu, Ayşegül

2015-01-01

Proximal interphalangeal joint dislocations are injuries observed frequently and caused by axial loading on the finger in the extension. In this paper we present a traumatic open finger dislocation due to a ball hitting a wrestler. It was successfully treated with reduction and the volar plate and collateral bond fixation were applied with absorbable sutures.

DISTRIBUTED RC NETWORKS WITH RATIONAL TRANSFER FUNCTIONS,

DTIC Science & Technology

A distributed RC circuit analogous to a continuously tapped transmission line can be made to have a rational short-circuit transfer admittance and...one rational shortcircuit driving-point admittance. A subcircuit of the same structure has a rational open circuit transfer impedance and one rational ...open circuit driving-point impedance. Hence, rational transfer functions may be obtained while considering either generator impedance or load

Observations of market pigs following transport to a packing plant.

PubMed

Kephart, K B; Harper, M T; Raines, C R

2010-06-01

A field study was conducted to record observations of 41,744 market-weight pigs upon arrival at a commercial abattoir to evaluate the relationships between various independent factors and open-mouth breathing, skin discoloration, lameness, unloading time, and mortality during transport. Observations were recorded from 242 trailer loads on 46 separate days over a period of 14 mo. Travel time (<2.5 h or >or=2.5 h), wait time before unloading (<20 min or >or=20 min), loading pressure (<260 kg of BW/m(2) trailer floor space or >or=260 kg of BW/m(2) trailer floor space), ambient temperature while unloading (<17 degrees C or >or=17 degrees C), and trailer type [potbelly (PB); straight-deck with conventional unloading doors (SDC); or straight-deck with wide unloading doors (SDW)] were recorded for each load. Open-mouth breathing was more prevalent in pigs when transported on PB trailers compared with that of SDC or SDW trailers (P < 0.01), and at warmer temperatures (>or=17 degrees C, P < 0.001). Skin discoloration was more prevalent (P < 0.001) among pigs unloaded at temperatures >or=17 degrees C. Lameness was more prevalent (P < 0.05) after shorter travel times at greater loading pressure compared with shorter travel times at decreased loading pressure. Unloading time for PB trailers was longer (P < 0.001) than for SDC and SDW. Mortality rates during transport were minimal (0.06%) in the deliveries that we observed, and there were no significant (P > 0.10) relationships between mortality and any independent variable tested. Wait time before unloading was not associated (P > 0.10) with any of the dependent variables included in the statistical model. In conclusion, warmer ambient temperatures (>or=17 degrees C) and the use of PB trailers are associated with an increased incidence of open-mouth breathing and skin discoloration, and longer unloading times after the transport of market pigs.

Peak exposures to main components of ash and gaseous diesel exhausts in closed and open ash loading stations at biomass-fuelled power plants.

PubMed

Laitinen, Juha; Koponen, Hanna; Sippula, Olli; Korpijärvi, Kirsi; Jumpponen, Mika; Laitinen, Sirpa; Aatamila, Marjaleena; Tissari, Jarkko; Karhunen, Tommi; Ojanen, Kari; Jokiniemi, Jorma; Korpinen, Leena

2017-10-01

Fly and bottom ashes are collected at power plants to reduce the environmental effects of energy production. However, handling the ashes causes health problems for operators, maintenance workers and truck drivers at the power plants. Hence, we evaluated ash loaders' peak inhalation exposures to the chemical components of ash and diesel exhausts in open and closed ash loading stations at biomass-fuelled combined heat and power plants. We also carried out chemical and morphological analyses of the ashes to evaluate their health hazard potential in order to find practical technical measures to reduce workers' exposure. On the basis of X-ray diffraction analyses, the main respirable crystalline ash compounds were SiO 2 , CaSO 4 , CaO, Ca 2 Al 2 SiO 7 , NaCl and Ca 3 Al 2 O 6 in the fly ashes and SiO 2 , KAlSi 3 O 8 , NaAlSi 3 O 8 and Ca 2 Al 2 SiO 7 in the bottom ashes. The short-term exposure levels of respirable crystalline silica, inhalable inorganic dust, Cr, Mn, Ni and nitric oxide exceeded their Finnish eight hours occupational exposure limit values in the closed ash loading station. According to our observations, more attention should be paid to the ash-moistening process, the use of tank trucks instead of open cassette flatbed trucks, and the sealing of the loading line from the silo to the truck which would prevent spreading the ash into the air. The idling time of diesel trucks should also be limited, and ash loading stations should be equipped with exhaust gas ventilators. If working conditions make it impossible to keep to the OEL values, workers must use respirators and protect their eyes and skin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simulation model of fatigue crack opening/closing phenomena for predicting RPG load under arbitrary stress distribution field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toyosada, M.; Niwa, T.

1995-12-31

In this paper, Newman`s calculation model is modified to solve his neglected effect of the change of stress distribution ahead of a crack, and to leave elastic plastic materials along the crack surface because of the compatibility of Dugdale model. In addition to above treatment, the authors introduce plastic shrinkage at an immediate generation of new crack surfaces due to emancipation of internal force with the magnitude of yield stress level during unloading process in the model. Moreover, the model is expanded to arbitrary stress distribution field. By using the model, RPG load is simulated for a center notched specimenmore » under constant amplitude loading with various stress ratios and decreased maximum load while keeping minimum load.« less

Prediction of aerodynamic tonal noise from open rotors

NASA Astrophysics Data System (ADS)

Sharma, Anupam; Chen, Hsuan-nien

2013-08-01

A numerical approach for predicting tonal aerodynamic noise from "open rotors" is presented. "Open rotor" refers to an engine architecture with a pair of counter-rotating propellers. Typical noise spectra from an open rotor consist of dominant tones, which arise due to both the steady loading/thickness and the aerodynamic interaction between the two bladerows. The proposed prediction approach utilizes Reynolds Averaged Navier-Stokes (RANS) Computational Fluid Dynamics (CFD) simulations to obtain near-field description of the noise sources. The near-to-far-field propagation is then carried out by solving the Ffowcs Williams-Hawkings equation. Since the interest of this paper is limited to tone noise, a linearized, frequency domain approach is adopted to solve the wake/vortex-blade interaction problem.This paper focuses primarily on the speed scaling of the aerodynamic tonal noise from open rotors. Even though there is no theoretical mode cut-off due to the absence of nacelle in open rotors, the far-field noise is a strong function of the azimuthal mode order. While the steady loading/thickness noise has circumferential modes of high order, due to the relatively large number of blades (≈10-12), the interaction noise typically has modes of small orders. The high mode orders have very low radiation efficiency and exhibit very strong scaling with Mach number, while the low mode orders show a relatively weaker scaling. The prediction approach is able to capture the speed scaling (observed in experiment) of the overall aerodynamic noise very well.

Voltage-Load Sensitivity Matrix Based Demand Response for Voltage Control in High Solar Penetration Distribution Feeders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Xiangqi; Wang, Jiyu; Mulcahy, David

This paper presents a voltage-load sensitivity matrix (VLSM) based voltage control method to deploy demand response resources for controlling voltage in high solar penetration distribution feeders. The IEEE 123-bus system in OpenDSS is used for testing the performance of the preliminary VLSM-based voltage control approach. A load disaggregation process is applied to disaggregate the total load profile at the feeder head to each load nodes along the feeder so that loads are modeled at residential house level. Measured solar generation profiles are used in the simulation to model the impact of solar power on distribution feeder voltage profiles. Different casemore » studies involving various PV penetration levels and installation locations have been performed. Simulation results show that the VLSM algorithm performance meets the voltage control requirements and is an effective voltage control strategy.« less

Predicting Failure Progression and Failure Loads in Composite Open-Hole Tension Coupons

NASA Technical Reports Server (NTRS)

Arunkumar, Satyanarayana; Przekop, Adam

2010-01-01

Failure types and failure loads in carbon-epoxy [45n/90n/-45n/0n]ms laminate coupons with central circular holes subjected to tensile load are simulated using progressive failure analysis (PFA) methodology. The progressive failure methodology is implemented using VUMAT subroutine within the ABAQUS(TradeMark)/Explicit nonlinear finite element code. The degradation model adopted in the present PFA methodology uses an instantaneous complete stress reduction (COSTR) approach to simulate damage at a material point when failure occurs. In-plane modeling parameters such as element size and shape are held constant in the finite element models, irrespective of laminate thickness and hole size, to predict failure loads and failure progression. Comparison to published test data indicates that this methodology accurately simulates brittle, pull-out and delamination failure types. The sensitivity of the failure progression and the failure load to analytical loading rates and solvers precision is demonstrated.

Trafficking Highways to the Intercalated Disc: New Insights Unlocking the Specificity of Connexin 43 Localization

PubMed Central

Zhang, Shan-Shan; Shaw, Robin M.

2016-01-01

With each heartbeat, billions of cardiomyocytes work in concert to propagate the electrical excitation needed to effectively circulate blood. Regulated expression and timely delivery of connexin proteins to form gap junctions at the specialized cell – cell contact region, known as the intercalated disc, is essential to ventricular cardiomyocyte coupling. We focus this review on several regulatory mechanisms that have been recently found to govern the lifecycle of connexin 43 (Cx43), the short-lived and most abundantly expressed connexin in cardiac ventricular muscle. The Cx43 lifecycle begins with gene expression, followed by oligomerization into hexameric channels, and then cytoskeletal-based transport toward the disc region. Once delivered, hemichannels interact with resident disc proteins and are organized to effect intercellular coupling. We highlight recent studies exploring regulation of Cx43 localization to the intercalated disc, with emphasis on alternatively translated Cx43 isoforms and cytoskeletal transport machinery that together regulate Cx43 gap junction coupling between cardiomyocytes. PMID:24460200

Calcium signaling in taste cells: regulation required.

PubMed

Medler, Kathryn F

2010-11-01

Peripheral taste receptor cells depend on distinct calcium signals to generate appropriate cellular responses that relay taste information to the central nervous system. Some taste cells have conventional chemical synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release from stores to formulate an output signal through a hemichannel. Despite the importance of calcium signaling in taste cells, little is known about how these signals are regulated. This review summarizes recent studies that have identified 2 calcium clearance mechanisms expressed in taste cells, including mitochondrial calcium uptake and sodium/calcium exchangers (NCXs). These studies identified a unique constitutive calcium influx that contributes to maintaining appropriate calcium homeostasis in taste cells and the role of the mitochondria and exchangers in this process. The additional role of NCXs in the regulation of evoked calcium responses is also discussed. Clearly, calcium signaling is a dynamic process in taste cells and appears to be more complex than has previously been appreciated.

Activation energy of the low-load NaCl transition from nanoindentation loading curves.

PubMed

Kaupp, Gerd

2014-01-01

Access to activation energies E(a) of phase transitions is opened by unprecedented analyses of temperature dependent nanoindentation loading curves. It is based on kinks in linearized loading curves, with additional support by coincidence of kink and electrical conductivity of silicon loading curves. Physical properties of B1, B2, NaCl and further phases are discussed. The normalized low-load transition energy of NaCl (Wtrans/µN) increases with temperature and slightly decreases with load. Its semi-logarithmic plot versus T obtains activation energy E(a)/µN for calculation of the transition work for all interesting temperatures and pressures. Arrhenius-type activation energy (kJ/mol) is unavailable for indentation phase transitions. The E(a) per load normalization proves insensitive to creep-on-load, which excludes normalization to depth or volume for large temperature ranges. Such phase transition E(a)/µN is unprecedented material's property and will be of practical importance for the compatibility of composite materials under impact and further shearing interactions at elevated temperatures. © 2014 Wiley Periodicals, Inc.

Increased sternocleidomastoid, but not trapezius, muscle activity in response to increased chewing load.

PubMed

Häggman-Henrikson, Birgitta; Nordh, Erik; Eriksson, Per-Olof

2013-10-01

Previous findings, during chewing, that boluses of larger size and harder texture result in larger amplitudes of both mandibular and head-neck movements suggest a relationship between increased chewing load and incremental recruitment of jaw and neck muscles. The present report evaluated jaw (masseter and digastric) and neck [sternocleidomastoid (SCM) and trapezius] muscle activity during the chewing of test foods of different sizes and textures by 10 healthy subjects. Muscle activity was recorded by surface electromyography and simultaneous mandibular and head movements were recorded using an optoelectronic technique. Each subject performed continuous jaw-opening/jaw-closing movements whilst chewing small and large boluses of chewing gum and rubber silicone (Optosil). For jaw opening/jaw closing without a bolus, SCM activity was recorded for jaw opening concomitantly with digastric activity. During chewing, SCM activity was recorded for jaw closing concomitantly with masseter activity. Trapezius activity was present in some, but not all, cycles. For the masseter and SCM muscles, higher activity was seen with larger test foods, suggesting increased demand and recruitment of these muscles in response to an increased chewing load. This result reinforces the previous notion of a close functional connection between the jaw and the neck motor systems in jaw actions and has scientific and clinical significance for studying jaw function and dysfunction. © 2013 Eur J Oral Sci.

Architecture Design and Experimental Platform Demonstration of Optical Network based on OpenFlow Protocol

NASA Astrophysics Data System (ADS)

Xing, Fangyuan; Wang, Honghuan; Yin, Hongxi; Li, Ming; Luo, Shenzi; Wu, Chenguang

2016-02-01

With the extensive application of cloud computing and data centres, as well as the constantly emerging services, the big data with the burst characteristic has brought huge challenges to optical networks. Consequently, the software defined optical network (SDON) that combines optical networks with software defined network (SDN), has attracted much attention. In this paper, an OpenFlow-enabled optical node employed in optical cross-connect (OXC) and reconfigurable optical add/drop multiplexer (ROADM), is proposed. An open source OpenFlow controller is extended on routing strategies. In addition, the experiment platform based on OpenFlow protocol for software defined optical network, is designed. The feasibility and availability of the OpenFlow-enabled optical nodes and the extended OpenFlow controller are validated by the connectivity test, protection switching and load balancing experiments in this test platform.

Experiences from the full-scale implementation of a new two-stage vertical flow constructed wetland design.

PubMed

Langergraber, Guenter; Pressl, Alexander; Haberl, Raimund

2014-01-01

This paper describes the results of the first full-scale implementation of a two-stage vertical flow constructed wetland (CW) system developed to increase nitrogen removal. The full-scale system was constructed for the Bärenkogelhaus, which is located in Styria at the top of a mountain, 1,168 m above sea level. The Bärenkogelhaus has a restaurant with 70 seats, 16 rooms for overnight guests and is a popular site for day visits, especially during weekends and public holidays. The CW treatment system was designed for a hydraulic load of 2,500 L.d(-1) with a specific surface area requirement of 2.7 m(2) per person equivalent (PE). It was built in fall 2009 and started operation in April 2010 when the restaurant was re-opened. Samples were taken between July 2010 and June 2013 and were analysed in the laboratory of the Institute of Sanitary Engineering at BOKU University using standard methods. During 2010 the restaurant at Bärenkogelhaus was open 5 days a week whereas from 2011 the Bärenkogelhaus was open only on demand for events. This resulted in decreased organic loads of the system in the later period. In general, the measured effluent concentrations were low and the removal efficiencies high. During the whole period the ammonia nitrogen effluent concentration was below 1 mg/L even at effluent water temperatures below 3 °C. Investigations during high-load periods, i.e. events like weddings and festivals at weekends, with more than 100 visitors, showed a very robust treatment performance of the two-stage CW system. Effluent concentrations of chemical oxygen demand and NH4-N were not affected by these events with high hydraulic loads.

Genetic Ancestry and Susceptibility to Late-Onset Alzheimer Disease (LOAD) in the Admixed Colombian Population.

PubMed

Moreno, Diana J; Pino, Sebastián; Ríos, Ángela; Lopera, Francisco; Ostos, Henry; Via, Marc; Bedoya, Gabriel

2017-01-01

Differences in the prevalence of dementia among populations and in the effect of apolipoprotein E (APOE) on the emergence of Alzheimer disease (AD), which is the main type of dementia, have been reported. This study estimated the ancestry of a group of individuals with late-onset Alzheimer disease (LOAD) (N=280) and established whether there were any differences when compared with a control group (N=357) in a sample of the Colombian population. When the analyses were adjusted for known risk factors such as age, sex, presence of APOE[Latin Small Letter Open E]4, socioeconomic status, educational attainment, and place of birth, African ancestry was associated with an increased LOAD risk (odds ratio: 1.55; 95% confidence interval, 1.09-2.03; P=0.029), whereas Native American ancestry was associated with lower risk (odds ratio: 0.75; 95% confidence interval, 0.61-0.98; P=0.046), for every 10% increase in ancestry. In addition, there were significant differences in the proportion of Native American ancestry between carriers and noncarriers of the APOE[Latin Small Letter Open E]4 allele (Mann-Whitney U test, P=0.047), with noncarriers having higher mean Native American ancestry when compared with carriers. Our results are consistent with the presence of variants of African origin in the genome of the Colombian population and different from APOE[Latin Small Letter Open E]4 that represents a risk factor for the development of LOAD, whereas variants of Native American origin may be conferring protection. However, unknown environmental factors or epigenetic differences among continental groups could also explain the observed associations.

Structure-directing star-shaped block copolymers: supramolecular vesicles for the delivery of anticancer drugs.

PubMed

Yang, Chuan; Liu, Shao Qiong; Venkataraman, Shrinivas; Gao, Shu Jun; Ke, Xiyu; Chia, Xin Tian; Hedrick, James L; Yang, Yi Yan

2015-06-28

Amphiphilic polycarbonate/PEG copolymer with a star-like architecture was designed to facilitate a unique supramolecular transformation of micelles to vesicles in aqueous solution for the efficient delivery of anticancer drugs. The star-shaped amphipilic block copolymer was synthesized by initiating the ring-opening polymerization of trimethylene carbonate (TMC) from methyl cholate through a combination of metal-free organo-catalytic living ring-opening polymerization and post-polymerization chain-end derivatization strategies. Subsequently, the self-assembly of the star-like polymer in aqueous solution into nanosized vesicles for anti-cancer drug delivery was studied. DOX was physically encapsulated into vesicles by dialysis and drug loading level was significant (22.5% in weight) for DOX. Importantly, DOX-loaded nanoparticles self-assembled from the star-like copolymer exhibited greater kinetic stability and higher DOX loading capacity than micelles prepared from cholesterol-initiated diblock analogue. The advantageous disparity is believed to be due to the transformation of micelles (diblock copolymer) to vesicles (star-like block copolymer) that possess greater core space for drug loading as well as the ability of such supramolecular structures to encapsulate DOX. DOX-loaded vesicles effectively inhibited the proliferation of 4T1, MDA-MB-231 and BT-474 cells, with IC50 values of 10, 1.5 and 1.0mg/L, respectively. DOX-loaded vesicles injected into 4T1 tumor-bearing mice exhibited enhanced accumulation in tumor tissue due to the enhanced permeation and retention (EPR) effect. Importantly, DOX-loaded vesicles demonstrated greater tumor growth inhibition than free DOX without causing significant body weight loss or cardiotoxicity. The unique ability of the star-like copolymer emanating from the methyl cholate core provided the requisite modification in the block copolymer interfacial curvature to generate vesicles of high loading capacity for DOX with significant kinetic stability that have potential for use as an anti-cancer drug delivery carrier for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

APPARATUS FOR LOADING AND UNLOADING A MACHINE

DOEpatents

Payne, J.H. Jr.

1962-07-17

An arrangement for loading and unloading a nuclear reactor is described. Depleted fuel elements are removed from the reactor through one of a small number of holes in a shielding plug that is rotatably mounted in an eccentric annular plug rotatably mounted in the top of the reactor. The fuel elements removed are stored in a plurality of openings in a rotatable magazine or storage means rotatably mounted over the plugs. (AEC)

Finite element simulation of gap opening between cladding tube and spacer grid in a fuel rod assembly using crystallographic models of irradiation growth and creep

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patra, Anirban; Tomé, Carlos N.

A physically-based crystal plasticity framework for modeling irradiation growth and creep is interfaced with the finite element code ABAQUS in order to study the contact forces and the gap evolution between the spacer grid and the cladding tube as a function of irradiation in a representative section of a fuel rod assembly. Deformation mechanisms governing the gap opening are identified and correlated to the texture-dependent material response. Thus, in the absence of coolant flow-induced vibrations, these simulations predict the contribution of irradiation growth and creep to the gap opening between the cladding tube and the springs and dimples on themore » spacer grid. The simulated contact forces on the springs and dimples are compared to available experimental and modeling data. Various combinations of external loads are applied on the springs and dimples to simulate fuel rods in the interior and at the periphery of the fuel rod assembly. Furthermore, we found that loading conditions representative (to a first order approximation) of fuel rods at the periphery show higher gap opening. This is in agreement with in-reactor data, where rod leakages due to the synergistic effects of gap opening and coolant flow-induced vibrations were generally found to occur at the periphery of the fuel rod assembly.« less

Finite element simulation of gap opening between cladding tube and spacer grid in a fuel rod assembly using crystallographic models of irradiation growth and creep

DOE PAGES

Patra, Anirban; Tomé, Carlos N.

2017-03-06

A physically-based crystal plasticity framework for modeling irradiation growth and creep is interfaced with the finite element code ABAQUS in order to study the contact forces and the gap evolution between the spacer grid and the cladding tube as a function of irradiation in a representative section of a fuel rod assembly. Deformation mechanisms governing the gap opening are identified and correlated to the texture-dependent material response. Thus, in the absence of coolant flow-induced vibrations, these simulations predict the contribution of irradiation growth and creep to the gap opening between the cladding tube and the springs and dimples on themore » spacer grid. The simulated contact forces on the springs and dimples are compared to available experimental and modeling data. Various combinations of external loads are applied on the springs and dimples to simulate fuel rods in the interior and at the periphery of the fuel rod assembly. Furthermore, we found that loading conditions representative (to a first order approximation) of fuel rods at the periphery show higher gap opening. This is in agreement with in-reactor data, where rod leakages due to the synergistic effects of gap opening and coolant flow-induced vibrations were generally found to occur at the periphery of the fuel rod assembly.« less

Aerodynamic Load Measurements and Opening Characteristics of Automatic Leading Edge Slats on a 45 deg Sweptback Wing at Transonic Speeds

NASA Technical Reports Server (NTRS)

Arabian, Donald D.; Runckel, Jack F.; Reid, Charles F, Jr.

1961-01-01

Measurements of the normal force and chord force were made on the slats of a sting-mounted wing-fuselage model through a Mach number range of 0.60 to 1.03 and at angles of attack from 0 to 20 deg at subsonic speeds and from 0 to 8 deg at Mach number 1.03. The 20-percent-chord tapered leading-edge slats extended from 25 to 95 percent of the semispan and consisted of five segments. The model wing had 45 deg sweep, an aspect ratio of 3.56, a taper ratio of 0.3, and NACA 64(06)AO07 airfoil sections. Slat forces and moments were determined for the slats in the almost-closed and open positions for spanwise extents of 35 to 95 percent and 46 to 95 percent of the semispan. The results of the investigation showed little change in the slat maximum force and moment coefficients with Mach number. The coefficients for the open and almost-closed slat positions had similar variations with angle of attack. The loads on the individual slat segments were found to increase toward the tip for moderate angles of attack and decrease toward the tip for high angles of attack. An analysis of the opening and closing characteristics of aerodynamically operated slats opening on a circular-arc path is included.

The substorm loading-unloading cycle as reproduced by community-available global MHD magnetospheric models

NASA Astrophysics Data System (ADS)

Gordeev, Evgeny; Sergeev, Victor; Tsyganenko, Nikolay; Kuznetsova, Maria; Rastaetter, Lutz; Raeder, Joachim; Toth, Gabor; Lyon, John; Merkin, Vyacheslav; Wiltberger, Michael

2017-04-01

In this study we investigate how well the three community-available global MHD models, supported by the Community Coordinated Modeling Center (CCMC NASA), reproduce the global magnetospheric dynamics, including the loading-unloading substorm cycle. We found that in terms of global magnetic flux transport CCMC models display systematically different response to idealized 2-hour north then 2-hour south IMF Bz variation. The LFM model shows a depressed return convection in the tail plasma sheet and high rate of magnetic flux loading into the lobes during the growth phase, as well as enhanced return convection and high unloading rate during the expansion phase, with the amount of loaded/unloaded magnetotail flux and the growth phase duration being the closest to their observed empirical values during isolated substorms. BATSRUS and Open GGCM models exhibit drastically different behavior. In the BATS-R-US model the plasma sheet convection shows a smooth transition to the steady convection regime after the IMF southward turning. In the Open GGCM a weak plasma sheet convection has comparable intensities during both the growth phase and the following slow unloading phase. Our study shows that different CCMC models under the same solar wind conditions (north to south IMF variation) produce essentially different solutions in terms of global magnetospheric convection.

Load capacity improvements in nucleic acid based systems using partially open feedback control.

PubMed

Kulkarni, Vishwesh; Kharisov, Evgeny; Hovakimyan, Naira; Kim, Jongmin

2014-08-15

Synthetic biology is facilitating novel methods and components to build in vivo and in vitro circuits to better understand and re-engineer biological networks. Recently, Kim and Winfree have synthesized a remarkably elegant network of transcriptional oscillators in vitro using a modular architecture of synthetic gene analogues and a few enzymes that, in turn, could be used to drive a variety of downstream circuits and nanodevices. However, these oscillators are sensitive to initial conditions and downstream load processes. Furthermore, the oscillations are not sustained since the inherently closed design suffers from enzyme deactivation, NTP fuel exhaustion, and waste product build up. In this paper, we show that a partially open architecture in which an [Symbol: see text]1 adaptive controller, implemented inside an in silico computer that resides outside the wet-lab apparatus, can ensure sustained tunable oscillations in two specific designs of the Kim-Winfree oscillator networks. We consider two broad cases of operation: (1) the oscillator network operating in isolation and (2) the oscillator network driving a DNA tweezer subject to a variable load. In both scenarios, our simulation results show a significant improvement in the tunability and robustness of these oscillator networks. Our approach can be easily adopted to improve the loading capacity of a wide range of synthetic biological devices.

Accelerated development and flight evaluation of active controls concepts for subsonic transport aircraft. Volume 1: Load alleviation/extended span development and flight tests

NASA Technical Reports Server (NTRS)

Johnston, J. F.

1979-01-01

Active wing load alleviation to extend the wing span by 5.8 percent, giving a 3 percent reduction in cruise drag is covered. The active wing load alleviation used symmetric motions of the outboard ailerons for maneuver load control (MLC) and elastic mode suppression (EMS), and stabilizer motions for gust load alleviation (GLA). Slow maneuvers verified the MLC, and open and closed-loop flight frequency response tests verified the aircraft dynamic response to symmetric aileron and stabilizer drives as well as the active system performance. Flight tests in turbulence verified the effectiveness of the active controls in reducing gust-induced wing loads. It is concluded that active wing load alleviation/extended span is proven in the L-1011 and is ready for application to airline service; it is a very practical way to obtain the increased efficiency of a higher aspect ratio wing with minimum structural impact.

On Generating Fatigue Crack Growth Thresholds

NASA Technical Reports Server (NTRS)

Forth, Scott C.; Newman, James, Jr.; Forman, Royce G.

2003-01-01

The fatigue crack growth threshold, defining crack growth as either very slow or nonexistent, has been traditionally determined with standardized load reduction methodologies. These experimental procedures can induce load history effects that result in crack closure. This history can affect the crack driving force, i.e. during the unloading process the crack will close first at some point along the wake or blunt at the crack tip, reducing the effective load at the crack tip. One way to reduce the effects of load history is to propagate a crack under constant amplitude loading. As a crack propagates under constant amplitude loading, the stress intensity factor range, Delta K, will increase, as will the crack growth rate. da/dN. A fatigue crack growth threshold test procedure is experimentally validated that does not produce load history effects and can be conducted at a specified stress ratio, R. The authors have chosen to study a ductile aluminum alloy where the plastic deformations generated during testing may be of the magnitude to impact the crack opening.

Symplectic modeling of beam loading in electromagnetic cavities

DOE PAGES

Abell, Dan T.; Cook, Nathan M.; Webb, Stephen D.

2017-05-22

Simulating beam loading in radio frequency accelerating structures is critical for understanding higher-order mode effects on beam dynamics, such as beam break-up instability in energy recovery linacs. Full wave simulations of beam loading in radio frequency structures are computationally expensive, and while reduced models can ignore essential physics, it can be difficult to generalize. Here, we present a self-consistent algorithm derived from the least-action principle which can model an arbitrary number of cavity eigenmodes and with a generic beam distribution. It has been implemented in our new Open Library for Investigating Vacuum Electronics (OLIVE).

Experimental Observations of a Stitched Composite with a Notch Subjected to Combined Bending and Tension Loading

NASA Technical Reports Server (NTRS)

Palmer, Susan O.; Nettles, Alan T.; Poe, C. C.

1998-01-01

A series of tests was conducted to support development of an analytical model for predicting the failure strains of stitched warp-knit carbon/epoxy composite materials with through-thicknesss damage in the form of a crack-like notch. Measurements of strain near notch tips, crack opening displacement (COD), and applied load were monitored in all tests. The out-of-plane displacement at the center of the notch was also measured when the specimen was subjected to bending. Three types of loading were applied: pure bending, pure tension, and combined bending and tension.

Solid state pulsed power generator

DOEpatents

Tao, Fengfeng; Saddoughi, Seyed Gholamali; Herbon, John Thomas

2014-02-11

A power generator includes one or more full bridge inverter modules coupled to a semiconductor opening switch (SOS) through an inductive resonant branch. Each module includes a plurality of switches that are switched in a fashion causing the one or more full bridge inverter modules to drive the semiconductor opening switch SOS through the resonant circuit to generate pulses to a load connected in parallel with the SOS.

Benchmarking Defmod, an open source FEM code for modeling episodic fault rupture

NASA Astrophysics Data System (ADS)

Meng, Chunfang

2017-03-01

We present Defmod, an open source (linear) finite element code that enables us to efficiently model the crustal deformation due to (quasi-)static and dynamic loadings, poroelastic flow, viscoelastic flow and frictional fault slip. Ali (2015) provides the original code introducing an implicit solver for (quasi-)static problem, and an explicit solver for dynamic problem. The fault constraint is implemented via Lagrange Multiplier. Meng (2015) combines these two solvers into a hybrid solver that uses failure criteria and friction laws to adaptively switch between the (quasi-)static state and dynamic state. The code is capable of modeling episodic fault rupture driven by quasi-static loadings, e.g. due to reservoir fluid withdraw or injection. Here, we focus on benchmarking the Defmod results against some establish results.

Design, Fabrication, and Performance of Foil Gas Thrust Bearings for Microturbomachinery Applications

NASA Technical Reports Server (NTRS)

Dykas, Brian; Bruckner, Robert; DellaCorte, Christopher; Edmonds, Brian; Prahl, Joseph

2008-01-01

A methodology for the design and construction of simple foil thrust bearings intended for parametric performance testing and low marginal costs is presented. Features drawn from a review of the open literature are discussed as they relate to bearing performance. The design of fixtures and tooling required to fabricate foil thrust bearings is presented, using conventional machining processes where possible. A prototype bearing with dimensions drawn from the literature is constructed, with all fabrication steps described. A load-deflection curve for the bearing is presented to illustrate structural stiffness characteristics. Start-top cycles are performed on the bearing at a temperature of 425 C to demonstrate early-life wear patterns. A test of bearing load capacity demonstrates useful performance when compared with data obtained from the open literature.

InSitu SEM Investigation of Microstructural Damage Evolution and Strain Relaxation in a Melt Infiltrated SiC/SiC Composite

NASA Technical Reports Server (NTRS)

Sevener, Kathy; Chen, Zhe; Daly, Sam; Tracy, Jared; Kiser, Doug

2016-01-01

With CMC components poised to complete flight certification in turbine engines on commercial aircraft within the near future, there are many efforts within the aerospace community to model the mechanical and environmental degradation of CMCs. Direct observations of damage evolution are needed to support these modeling efforts and provide quantitative measures of damage parameters used in the various models. This study was performed to characterize the damage evolution during tensile loading of a melt infiltrated (MI) silicon carbide reinforced silicon carbide (SiC/SiC) composite. A SiC/SiC tensile coupon was loaded to a maximum global stress of 30 ksi in a tensile fixture within an SEM while observations were made at 5 ksi increments. Both traditional image analysis and DIC (digital image correlation) were used to quantify damage evolution. With the DIC analysis, microscale damage was observed at the fiber-matrix interfaces at stresses as low as 5 ksi. First matrix cracking took place between 20 and 25 ksi, accompanied by an observable relaxation in strain near matrix cracks. Matrix crack opening measurements at the maximum load ranged from 200 nm to 1.5 m. Crack opening along the fiber-matrix interface was also characterized as a function of load and angular position relative to the loading axis. This characterization was funded by NASA GRC and was performed to support NASA GRC modeling of SiC/SiC environmental degradation

Novel PLA modification of organic microcontainers based on ring opening polymerization: synthesis, characterization, biocompatibility and drug loading/release properties.

PubMed

Efthimiadou, E K; Tziveleka, L-A; Bilalis, P; Kordas, G

2012-05-30

In the current study, poly lactic acid (PLA) modified hollow crosslinked poly(hydroxyethyl methacrylate) (PHEMA) microspheres have been prepared, in order to obtain a stimulus-responsive, biocompatible carrier with sustained drug release properties. The synthetical process consisted of the preparation of poly(methacrylic acid)@poly(hydroxyethyl methacrylate-co-N,N'-methylene bis(acrylamide)) microspheres by a two stage distillation-precipitation polymerization technique using 2,2'-azobisisobutyronitrile as initiator. Following core removal, a PLA coating of the microspheres was formed, after ring opening polymerization of DL-lactide, attributing the initiator's role to the active hydroxyl groups of PHEMA. The anticancer drug daunorubicin (DNR) was selected for the study of loading and release behavior of the coated microspheres. The loading capacity of the PLA modified microspheres was found to be four times higher than that of the parent ones (16% compared to 4%). This coated microspherical carrier exhibited a moderate pH responsive drug release behavior due to the pH dependent water uptake of PHEMA, and PLA hydrolysis. The in vitro cytotoxicity of both the parent and the DNR-loaded or empty modified hollow microspheres has been also examined on MCF-7 breast cancer cells. The results showed that although the empty microspheres were moderately cytotoxic, the DNR-loaded microspheres had more potent anti-tumor effect than the free drug. Therefore, the prepared coated microspheres are interesting drug delivery systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Biogas biodesulfurization in an anoxic biotrickling filter packed with open-pore polyurethane foam.

PubMed

Fernández, Maikel; Ramírez, Martín; Gómez, José Manuel; Cantero, Domingo

2014-01-15

Biogas biodesulfurization by an anoxic biotrickling filter packed with open pore polyurethane foam at the laboratory scale (packed volume 2.4L) has been studied. The biotrickling system was operated for 620 days with biogas supplied continuously and two nitrate feeding regimes were tested (manual and programmed). Biomass immobilization was carried out under the manual nitrate feeding regime and a study was then carried out on the effects on removal efficiency of the following parameters: nitrate source, H2S inlet load, nitrate concentration, sulfate accumulation, temperature, pH and trickling liquid velocity. The effect of increased H2S inlet load was studied under the programmed nitrate feeding regime. The results show that a removal efficiency of 99% can be obtained when working under the following conditions: inlet loads below 130gSm(-3)h(-1), a programmed nitrate feeding system, temperature of 30°C, sulfate concentration below 33gL(-1), a pH between 7.3 and 7.5, and a trickling liquid velocity higher than 4.6mh(-1). Copyright © 2013 Elsevier B.V. All rights reserved.

Experimental study on the influence of the opening in brick-masonry wall to seismic performance of reinforced concrete frame structures

NASA Astrophysics Data System (ADS)

Maidiawati, Tanjung, Jafril; Medriosa, Hamdeni

2017-10-01

Reinforced concrete (RC) frame structures with brick-masonry infills are commonly used in developing countries and high-risk seismic area, such as Indonesia. Significant researches have been carried out for studying the seismic performance of RC frame structures with brick-masonry infills. Only few of them focused on effects of the opening in the brick-masonry infill to the seismic performance of the RC frame structures. The presence of opening in brick-masonry infill is often used for placing doors and windows as well, however, it may reduce the seismic performance of the RC frame structure. In the current study, they influence of the opening in brick-masonry infills to the seismic performance RC frame structure will experimentally evaluated. Five of 1/4-scaled single story and single bay RC frame specimens were prepared, i.e. an RC bare frame, a clay brick-masonry infilled RC frame and three of clay brick-masonry infilled RC frame with openings in the brick-masonry infills. The last three specimens were clay brick infilled RC frame with a center opening, clay brick infilled RC frame with two openings used for placing the windows and clay brick infilled RC frame with opening for placing the door. The specimens pushed over by applying the static monotonic lateral load to the upper beam of the RC frame structures. The incremental of the lateral load and the lateral displacement of RC frame's column was recorded during test. The crack propagation and the major cracks were also observed to identify the mechanism failure of specimens. As the results, the opening in the brick-masonry wall controls the failure mechanism, the lateral strength and the stiffness of the overall of infilled RC frame structure. The diagonal shear crack pattern was found on brick-masonry wall without opening, on other hand the different crack patterns were observed on brick-masonry wall with openings. Although the opening in the brick masonry infill reduced the lateral strength and stiffness of the infilled RC frame, it was still stronger and stiffer than the bare frame.

Investigating the performance of catalyst layer micro-structures with different platinum loadings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khakaz-Baboli, Moben; Harvey, David; Pharoah, Jon

In this study a four-phase micro-structure of a PEFC catalyst layer was reconstructed by randomly placing overlapping spheres for each solid catalyst phase. The micro-structure was mirrored to make a micro-structure. A body-fit computational mesh was produced for the reconstructed micro-structure in OpenFOAM. Associated conservation equations were solved within all the phases with electrochemical reaction as the boundary condition at the interface between ionomer and platinum phases. The study is focused on the platinum loading of CL. The polarization curves of the micro-structure performance have been compared for different platinum loadings. This paper gives increased insight into the relatively greatermore » losses at decreased platinum loadings.« less

Comparative study on diagonal equivalent methods of masonry infill panel

NASA Astrophysics Data System (ADS)

Amalia, Aniendhita Rizki; Iranata, Data

2017-06-01

Infrastructure construction in earthquake prone area needs good design process, including modeling a structure in a correct way to reduce damages caused by an earthquake. Earthquakes cause many damages e.g. collapsed buildings that are dangerous. An incorrect modeling in design process certainly affects the structure's ability in responding to load, i.e. an earthquake load, and it needs to be paid attention to in order to reduce damages and fatalities. A correct modeling considers every aspect that affects the strength of a building, including stiffness of resisting lateral loads caused by an earthquake. Most of structural analyses still use open frame method that does not consider the effect of stiffness of masonry panel to the stiffness and strength of the whole structure. Effect of masonry panel is usually not included in design process, but the presence of this panel greatly affects behavior of the building in responding to an earthquake. In worst case scenario, it can even cause the building to collapse as what has been reported after great earthquakes worldwide. Modeling a structure with masonry panel as consideration can be performed by designing the panel as compression brace or shell element. In designing masonry panel as a compression brace, there are fourteen methods popular to be used by structure designers formulated by Saneinejad-Hobbs, Holmes, Stafford-Smith, Mainstones, Mainstones-Weeks, Bazan-Meli, Liauw Kwan, Paulay and Priestley, FEMA 356, Durani Luo, Hendry, Al-Chaar, Papia and Chen-Iranata. Every method has its own equation and parameters to use, therefore the model of every method was compared to results of experimental test to see which one gives closer values. Moreover, those methods also need to be compared to the open frame to see if they can result values within limits. Experimental test that was used in comparing all methods was taken from Mehrabi's research (Fig. 1), which was a prototype of a frame in a structure with 0.5 scale and the ratio of height to width of 1 to 1.5. Load used in the experiment was based on Uniform Building Code (UBC) 1991. Every method compared was calculated first to get equivalent diagonal strut width. The second step was modelling method using structure analysis software as a frame with a diagonal in a linear mode. The linear mode was chosen based on structure analysis commonly used by structure designers. The frame was loaded and for every model, its load and deformation values were identified. The values of load - deformation of every method were compared to those of experimental test specimen by Mehrabi and open frame. From comparative study performed, Holmes' and Bazan-Meli's equations gave results the closest to the experimental test specimen by Mehrabi. Other equations that gave close values within the limit (by comparing it to the open frame) are Saneinejad-Hobbs, Stafford-Smith, Bazan-Meli, Liauw Kwan, Paulay and Priestley, FEMA 356, Durani Luo, Hendry, Papia and Chen-Iranata.

Kinetic studies of the stress corrosion cracking of D6AC steel

NASA Technical Reports Server (NTRS)

Noronha, P. J.

1975-01-01

The effect of load interactions on the crack growth velocity of D6AC steel under stress corrosion cracking conditions was determined. The environment was a 3.5 percent salt solution. The modified-wedge opening load specimens were fatigue precracked and subjected to a deadweight loading in creep machines. The effects of load shedding on incubation times and crack growth rates were measured using high-sensitivity compliance measurement techniques. Load shedding results in an incubation time, the length of which depends on the amount of load shed and the baseline stress intensity. The sequence of unloading the specimen also controls the subsequent incubation period. The incubation period is shorter when load shedding passes through zero load than when it does not if the specimen initially had the same baseline stress intensity. The crack growth rates following the incubation period are also different from the steady-state crack growth rate at the operating stress intensity. These data show that the susceptibility of this alloy system to stress corrosion cracking depends on the plane-strain fracture toughness and on the yield strength of the material.

Disposal of Vessel Wastes: Shipboard and Shoreside Facilities. Phase 2. Graywater

DTIC Science & Technology

1979-07-01

Increase in Concentration Resulting from Daily Loadings and Vessel-Induced Mixing 45 3-7 Annual Loadings to Presque Isle - Marquette Harbor from...in port for 24 hours (Upper Lakes Reference Group, 1977a). Two harbors were considered for case studies. The first harbor, Presque Isle -Marquette...harbor. Presque Isle -Marquette The existing conditions of the harbor are considered to be of high quality with respect to coastal waters, the open waters

Sunlamp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nutaro, James J

The purpose of this model was to facilitate the design of a control system that uses fine grained control of residential and small commercial HVAC loads to counterbalance voltage swings caused by intermittent solar power sources (e.g., rooftop panels) installed in that distribution circuit. Included is the source code and pre-compiled 64 bit dll for adding building HVAC loads to an OpenDSS distribution circuit. As written, the Makefile assumes you are using the Microsoft C++ development tools.

Assessment of disk MHD generators for a base load powerplant

NASA Technical Reports Server (NTRS)

Chubb, D. L.; Retallick, F. D.; Lu, C. L.; Stella, M.; Teare, J. D.; Loubsky, W. J.; Louis, J. F.; Misra, B.

1981-01-01

Results from a study of the disk MHD generator are presented. Both open and closed cycle disk systems were investigated. Costing of the open cycle disk components (nozzle, channel, diffuser, radiant boiler, magnet and power management) was done. However, no detailed costing was done for the closed cycle systems. Preliminary plant design for the open cycle systems was also completed. Based on the system study results, an economic assessment of the open cycle systems is presented. Costs of the open cycle disk conponents are less than comparable linear generator components. Also, costs of electricity for the open cycle disk systems are competitive with comparable linear systems. Advantages of the disk design simplicity are considered. Improvements in the channel availability or a reduction in the channel lifetime requirement are possible as a result of the disk design.

Biobatteries and biofuel cells with biphenylated carbon nanotubes

NASA Astrophysics Data System (ADS)

Stolarczyk, Krzysztof; Kizling, Michał; Majdecka, Dominika; Żelechowska, Kamila; Biernat, Jan F.; Rogalski, Jerzy; Bilewicz, Renata

2014-03-01

Single-walled carbon nanotubes (SWCNTs) covalently biphenylated are used for the construction of cathodes in a flow biobattery and in flow biofuel cell. Zinc covered with a hopeite layer is the anode in the biobattery and glassy carbon electrode covered with bioconjugates of single-walled carbon nanotubes with glucose oxidase and catalase is the anode of the biofuel cell. The potentials of the electrodes are measured vs. the Ag/AgCl reference electrode under changing loads of the fuel cell/biobattery. The power density of the biobattery with biphenylated nanotubes at the cathode is ca. 0.6 mW cm-2 and the open circuit potential is ca. 1.6 V. In order to obtain larger power densities and voltages three biobatteries are connected in a series which leads to the open circuit potential of ca. 4.8 V and power density 2.1 mW cm-2 at 3.9 V under 100 kΩ load. The biofuel cell shows power densities of ca. 60 μW cm-2 at 20 kΩ external resistance but the open circuit potential for such biofuel cell is only 0.5 V. The biobattery showing significantly larger power densities and open circuit voltages are especially useful for testing novel cathodes and applications such as powering units for clocks and sensing devices.

The electrostatics of parachutes

NASA Astrophysics Data System (ADS)

Yu, Li; Ming, Xiao

2007-12-01

In the research of parachute, canopy inflation process modeling is one of the most complicated tasks. As canopy often experiences the largest deformations and loadings during a very short time, it is of great difficulty for theoretical analysis and experimental measurements. In this paper, aerodynamic equations and structural dynamics equations were developed for describing parachute opening process, and an iterative coupling solving strategy incorporating the above equations was proposed for a small-scale, flexible and flat-circular parachute. Then, analyses were carried out for canopy geometry, time-dependent pressure difference between the inside and outside of the canopy, transient vortex around the canopy and the flow field in the radial plane as a sequence in opening process. The mechanism of the canopy shape development was explained from perspective of transient flow fields during the inflation process. Experiments of the parachute opening process were conducted in a wind tunnel, in which instantaneous shape of the canopy was measured by high velocity camera and the opening loading was measured by dynamometer balance. The theoretical predictions were found in good agreement with the experimental results, validating the proposed approach. This numerical method can improve the situation of strong dependence of parachute research on wind tunnel tests, and is of significance to the understanding of the mechanics of parachute inflation process.

Fluid-structure coupling for wind turbine blade analysis using OpenFOAM

NASA Astrophysics Data System (ADS)

Dose, Bastian; Herraez, Ivan; Peinke, Joachim

2015-11-01

Modern wind turbine rotor blades are designed increasingly large and flexible. This structural flexibility represents a problem for the field of Computational Fluid Dynamics (CFD), which is used for accurate load calculations and detailed investigations of rotor aerodynamics. As the blade geometries within CFD simulations are considered stiff, the effect of blade deformation caused by aerodynamic loads cannot be captured by the common CFD approach. Coupling the flow solver with a structural solver can overcome this restriction and enables the investigation of flexible wind turbine blades. For this purpose, a new Finite Element (FE) solver was implemented into the open source CFD code OpenFOAM. Using a beam element formulation based on the Geometrically Exact Beam Theory (GEBT), the structural model can capture geometric non-linearities such as large deformations. Coupled with CFD solvers of the OpenFOAM package, the new framework represents a powerful tool for aerodynamic investigations. In this work, we investigated the aerodynamic performance of a state of the art wind turbine. For different wind speeds, aerodynamic key parameters are evaluated and compared for both, rigid and flexible blade geometries. The present work is funded within the framework of the joint project Smart Blades (0325601D) by the German Federal Ministry for Economic Affairs and Energy (BMWi) under decision of the German Federal Parliament.

46 CFR 169.683 - Overcurrent protection, general.

Code of Federal Regulations, 2013 CFR

2013-10-01

... time delay; (2) Instantaneous short circuit protection; and (3) Repeated opening of the circuit in... above the full-load rating for continuous rated machines or the overload rating for special rated machines. ...

46 CFR 169.683 - Overcurrent protection, general.

Code of Federal Regulations, 2014 CFR

2014-10-01

... time delay; (2) Instantaneous short circuit protection; and (3) Repeated opening of the circuit in... above the full-load rating for continuous rated machines or the overload rating for special rated machines. ...

46 CFR 169.683 - Overcurrent protection, general.

Code of Federal Regulations, 2012 CFR

2012-10-01

... time delay; (2) Instantaneous short circuit protection; and (3) Repeated opening of the circuit in... above the full-load rating for continuous rated machines or the overload rating for special rated machines. ...

Prophase pathway-dependent removal of cohesin from human chromosomes requires opening of the Smc3–Scc1 gate

PubMed Central

Buheitel, Johannes; Stemmann, Olaf

2013-01-01

Faithful transmission of chromosomes during eukaryotic cell division requires sister chromatids to be paired from their generation in S phase until their separation in M phase. Cohesion is mediated by the cohesin complex, whose Smc1, Smc3 and Scc1 subunits form a tripartite ring that entraps both DNA double strands. Whereas centromeric cohesin is removed in late metaphase by Scc1 cleavage, metazoan cohesin at chromosome arms is displaced already in prophase by proteolysis-independent signalling. Which of the three gates is triggered by the prophase pathway to open has remained enigmatic. Here, we show that displacement of human cohesin from early mitotic chromosomes requires dissociation of Smc3 from Scc1 but no opening of the other two gates. In contrast, loading of human cohesin onto chromatin in telophase occurs through the Smc1–Smc3 hinge. We propose that the use of differently regulated gates for loading and release facilitates unidirectionality of DNA's entry into and exit from the cohesin ring. PMID:23361318

Conceptual Design and Structural Analysis of an Open Rotor Hybrid Wing Body Aircraft

NASA Technical Reports Server (NTRS)

Gern, Frank H.

2013-01-01

Through a recent NASA contract, Boeing Research and Technology in Huntington Beach, CA developed and optimized a conceptual design of an open rotor hybrid wing body aircraft (HWB). Open rotor engines offer a significant potential for fuel burn savings over turbofan engines, while the HWB configuration potentially allows to offset noise penalties through possible engine shielding. Researchers at NASA Langley converted the Boeing design to a FLOPS model which will be used to develop take-off and landing trajectories for community noise analyses. The FLOPS model was calibrated using Boeing data and shows good agreement with the original Boeing design. To complement Boeing s detailed aerodynamics and propulsion airframe integration work, a newly developed and validated conceptual structural analysis and optimization tool was used for a conceptual loads analysis and structural weights estimate. Structural optimization and weight calculation are based on a Nastran finite element model of the primary HWB structure, featuring centerbody, mid section, outboard wing, and aft body. Results for flight loads, deformations, wing weight, and centerbody weight are presented and compared to Boeing and FLOPS analyses.

Surface modification of paclitaxel-loaded tri-block copolymer PLGA- b-PEG- b-PLGA nanoparticles with protamine for liver cancer therapy

NASA Astrophysics Data System (ADS)

Gao, Nansha; Chen, Zhihong; Xiao, Xiaojun; Ruan, Changshun; Mei, Lin; Liu, Zhigang; Zeng, Xiaowei

2015-08-01

In order to enhance the therapeutic effect of chemotherapy on liver cancer, a biodegradable formulation of protamine-modified paclitaxel-loaded poly(lactide- co-glycolide)- b-poly(ethylene glycol)- b-poly(lactide- co-glycolide) (PLGA- b-PEG- b-PLGA) nanoparticles (PTX-loaded/protamine NPs) was prepared. Tri-block copolymer PLGA- b-PEG- b-PLGA was synthesized by ring-opening polymerization and characterized by 1H NMR spectroscopy and gel permeation chromatography. PTX-loaded and PTX-loaded/protamine NPs were characterized in terms of size, size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin 6-loaded/protamine NPs were internalized by hepatocellular carcinoma cell line HepG2. The cellular uptake efficiency of NPs was obviously elevated after protamine modification. With commercial formulation Taxol® as the reference, HepG2 cells were also used to study the cytotoxicity of the NPs. PTX-loaded/protamine NPs exhibited significantly higher cytotoxicity than PTX-loaded NPs and Taxol® did. All the results suggested that surface modification of PTX-loaded PLGA- b-PEG- b-PLGA NPs with protamine boosted the therapeutic efficacy on liver cancer.

Laser beam guard clamps

DOEpatents

Dickson, Richard K.

2010-09-07

A quick insert and release laser beam guard panel clamping apparatus having a base plate mountable on an optical table, a first jaw affixed to the base plate, and a spring-loaded second jaw slidably carried by the base plate to exert a clamping force. The first and second jaws each having a face acutely angled relative to the other face to form a V-shaped, open channel mouth, which enables wedge-action jaw separation by and subsequent clamping of a laser beam guard panel inserted through the open channel mouth. Preferably, the clamping apparatus also includes a support structure having an open slot aperture which is positioned over and parallel with the open channel mouth.

Advanced emergency openings for commercial aircraft

NASA Technical Reports Server (NTRS)

Bement, L. J.; Schimmel, M. L.

1985-01-01

Explosively actuated openings in composite panels are proposed to enhance passenger survivability within commercial aircraft by providing improvements in emergency openings, fuselage venting, and fuel dump. The concept is to embed a tiny, highly stable explosive cord in the periphery of a load-carrying composite panel; on initiation of the cord, the panel is fractured to create a well-defined opening. The panel would be installed in the sides of the fuselage for passenger egress, in the top of the fuselage for smoke venting, and in the bottoms of the fuel cells for fuel dump. Described are the concerns with the use of explosive systems, safety improvements, advantages, experimental results, and recommended approach to gain acceptance and develop this concept.

Differentially-charged and sequentially-switched square-wave pulse forming network

DOEpatents

North, George G. [Stockton, CA; Vogilin, George E. [Livermore, CA

1980-04-01

A pulse forming network for delivering a high-energy square-wave pulse to a load, including a series of inductive-capacitive sections wherein the capacitors are differentially charged higher further from the load. Each charged capacitor is isolated from adjacent sections and the load by means of a normally open switch at the output of each section. The switch between the load and the closest section to the load is closed to begin discharge of the capacitor in that section into the load. During discharge of each capacitor, the voltage thereacross falls to a predetermined potential with respect to the potential across the capacitor in the next adjacent section further from the load. When this potential is reached, it is used to close the switch in the adjacent section further from the load and thereby apply the charge in that section to the load through the adjacent section toward the load. Each successive section further from the load is sequentially switched in this manner to continuously and evenly supply energy to the load over the period of the pulse, with the differentially charged capacitors providing higher potentials away from the load to compensate for the voltage drop across the resistance of each inductor. This arrangement is low in cost and yet provides a high-energy pulse in an acceptable square-wave form.

Differentially-charged and sequentially-switched square-wave pulse forming network

DOEpatents

North, G.G.; Vogilin, G.E.

1980-04-01

Disclosed is a pulse forming network for delivering a high-energy square-wave pulse to a load, including a series of inductive-capacitive sections wherein the capacitors are differentially charged higher further from the load. Each charged capacitor is isolated from adjacent sections and the load by means of a normally open switch at the output of each section. The switch between the load and the closest section to the load is closed to begin discharge of the capacitor in that section into the load. During discharge of each capacitor, the voltage thereacross falls to a predetermined potential with respect to the potential across the capacitor in the next adjacent section further from the load. When this potential is reached, it is used to close the switch in the adjacent section further from the load and thereby apply the charge in that section to the load through the adjacent section toward the load. Each successive section further from the load is sequentially switched in this manner to continuously and evenly supply energy to the load over the period of the pulse, with the differentially charged capacitors providing higher potentials away from the load to compensate for the voltage drop across the resistance of each inductor. This arrangement is low in cost and yet provides a high-energy pulse in an acceptable square-wave form. 5 figs.

Friedreich's Ataxia Research Alliance

MedlinePlus

... Cookies ? Yes Wait Leave Provided by OpenGlobal E-commerce Please wait while your page loads ... FARA Cure ... Help Ways to Donate rideATAXIA Team FARA FARA Energy Ball Grassroots Fundraising Fundraising Tools Raising Awareness Advocacy ...

Thermocouple split follower

DOEpatents

Howell, deceased, Louis J.

1980-01-01

Thermoelectric generator assembly accommodating differential thermal expansion between thermoelectric elements by means of a cylindrical split follower forming a slot and having internal spring loaded wedges that permit the split follower to open and close across the slot.

Shield evaluation and performance testing at the USMB`s Strategic Structures Testing Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barczak, T.M.; Gearhart, D.F.

1996-12-31

Historically, shield performance testing is conducted by the support manufacturers at European facilities. The U.S. Bureau of Mines (USBM) has conducted extensive research in shield Mechanics and is now opening its Strategic Structures Testing (SST) Laboratory to the mining industry for shield performance testing. The SST Laboratory provides unique shield testing capabilities using the Mine Roof Simulator (MRS) load frame. The MRS provides realistic and cost-effective shield evaluation by combining both vertical and horizontal loading into a single load cycle; whereas, several load cycles would be required to obtain this loading in a static frame. In addition to these advantages,more » the USBM acts as an independent research organization to provide an unbiased assessment of shield performance. This paper describes the USBM`s shield testing program that is designed specifically to simulate in-service mining conditions using the unique the capabilities of the SST Laboratory.« less

Recent advances in the modelling of crack growth under fatigue loading conditions

NASA Technical Reports Server (NTRS)

Dekoning, A. U.; Tenhoeve, H. J.; Henriksen, T. K.

1994-01-01

Fatigue crack growth associated with cyclic (secondary) plastic flow near a crack front is modelled using an incremental formulation. A new description of threshold behaviour under small load cycles is included. Quasi-static crack extension under high load excursions is described using an incremental formulation of the R-(crack growth resistance)- curve concept. The integration of the equations is discussed. For constant amplitude load cycles the results will be compared with existing crack growth laws. It will be shown that the model also properly describes interaction effects of fatigue crack growth and quasi-static crack extension. To evaluate the more general applicability the model is included in the NASGRO computer code for damage tolerance analysis. For this purpose the NASGRO program was provided with the CORPUS and the STRIP-YIELD models for computation of the crack opening load levels. The implementation is discussed and recent results of the verification are presented.

Double wall vacuum tubing and method of manufacture

DOEpatents

Stahl, Charles R.; Gibson, Michael A.; Knudsen, Christian W.

1989-01-01

An evacuated double wall tubing is shown together with a method for the manufacture of such tubing which includes providing a first pipe of predetermined larger diameter and a second pipe having an O.D. substantially smaller than the I.D. of the first pipe. An evacuation opening is then in the first pipe. The second pipe is inserted inside the first pipe with an annular space therebetween. The pipes are welded together at one end. A stretching tool is secured to the other end of the second pipe after welding. The second pipe is then prestressed mechanically with the stretching tool an amount sufficient to prevent substantial buckling of the second pipe under normal operating conditions of the double wall pipe. The other ends of the first pipe and the prestressed second pipe are welded together, preferably by explosion welding, without the introduction of mechanical spacers between the pipes. The annulus between the pipes is evacuated through the evacuation opening, and the evacuation opening is finally sealed. The first pipe is preferably of steel and the second pipe is preferably of titanium. The pipes may be of a size and wall thickness sufficient for the double wall pipe to be structurally load bearing or may be of a size and wall thickness insufficient for the double wall pipe to be structurally load bearing, and the double wall pipe positioned with a sliding fit inside a third pipe of a load-bearing size.

Magma explains low estimates of lithospheric strength based on flexure of ocean island loads

NASA Astrophysics Data System (ADS)

Buck, W. Roger; Lavier, Luc L.; Choi, Eunseo

2015-04-01

One of the best ways to constrain the strength of the Earth's lithosphere is to measure the deformation caused by large, well-defined loads. The largest, simple vertical load is that of the Hawaiian volcanic island chain. An impressively detailed recent analysis of the 3D response to that load by Zhong and Watts (2013) considers the depth range of seismicity below Hawaii and the seismically determined geometry of lithospheric deflection. These authors find that the friction coefficient for the lithosphere must be in the normal range measured for rocks, but conclude that the ductile flow strength has to be far weaker than laboratory measurements suggest. Specifically, Zhong and Watts (2013) find that stress differences in the mantle lithosphere below the island chain are less than about 200 MPa. Standard rheologic models suggest that for the ~50 km thick lithosphere inferred to exist below Hawaii yielding will occur at stress differences of about 1 GPa. Here we suggest that magmatic accommodation of flexural extension may explain Hawaiian lithospheric deflection even with standard mantle flow laws. Flexural stresses are extensional in the deeper part of the lithosphere below a linear island load (i.e. horizontal stresses orthogonal to the line load are lower than vertical stresses). Magma can accommodate lithospheric extension at smaller stress differences than brittle and ductile rock yielding. Dikes opening parallel to an island chain would allow easier downflexing than a continuous plate, but wound not produce a freely broken plate. The extensional stress needed to open dikes at depth depends on the density contrast between magma and lithosphere, assuming magma has an open pathway to the surface. For a uniform lithospheric density ρL and magma density ρM the stress difference to allow dikes to accommodate extension is: Δσxx (z) = g z (ρM - gρL), where g is the acceleration of gravity and z is depth below the surface. For reasonable density values (i.e. ρL = 3300 Kg/m3 and ρM = 2800 kg/m3) this 'magmatic yield stress' is 250 MPa at 50 km depth. Dikes accommodating flexing below Hawaii would be at most about 2 km wide. This amount of intrusion would significantly heat the lithosphere, leading to lower stress differences below the islands. Since Hawaii marks the highest magma flux on Earth today it seems that 'magma assisted flexure' offers a viable alternative to extremely weak lithospheric rheology as an explanation for low stresses below this load.

Nutrient, organic carbon, and chloride concentrations and loads in selected Long Island Sound tributaries—Four decades of change following the passage of the Federal Clean Water Act

USGS Publications Warehouse

Mullaney, John R.

2016-03-10

Loads of dissolved silica (DSi; flow-normalized and non-flow-normalized) increased slightly at most stations during the study period and were positively correlated to urbanized land in the basin and negatively correlated to area of open water. Concentrations and loads of chloride increased at 12 of the 14 sites during both periods. Increases likely are the result of an increase in the use of salt for deicing, as well as other factors related to urbanization and population growth, such as increases in wastewater discharge and discharge from septic systems.

Load Balancing Strategies for Multiphase Flows on Structured Grids

NASA Astrophysics Data System (ADS)

Olshefski, Kristopher; Owkes, Mark

2017-11-01

The computation time required to perform large simulations of complex systems is currently one of the leading bottlenecks of computational research. Parallelization allows multiple processing cores to perform calculations simultaneously and reduces computational times. However, load imbalances between processors waste computing resources as processors wait for others to complete imbalanced tasks. In multiphase flows, these imbalances arise due to the additional computational effort required at the gas-liquid interface. However, many current load balancing schemes are only designed for unstructured grid applications. The purpose of this research is to develop a load balancing strategy while maintaining the simplicity of a structured grid. Several approaches are investigated including brute force oversubscription, node oversubscription through Message Passing Interface (MPI) commands, and shared memory load balancing using OpenMP. Each of these strategies are tested with a simple one-dimensional model prior to implementation into the three-dimensional NGA code. Current results show load balancing will reduce computational time by at least 30%.

[Three dimensional finite element model of a modified posterior cervical single open-door laminoplasty].

PubMed

Wang, Q; Yang, Y; Fei, Q; Li, D; Li, J J; Meng, H; Su, N; Fan, Z H; Wang, B Q

2017-06-06

Objective: To build a three-dimensional finite element models of a modified posterior cervical single open-door laminoplasty with short-segmental lateral mass screws fusion. Methods: The C(2)-C(7) segmental data were obtained from computed tomography (CT) scans of a male patient with cervical spondylotic myelopathy and spinal stenosis.Three-dimensional finite element models of a modified cervical single open-door laminoplasty (before and after surgery) were constructed by the combination of software package MIMICS, Geomagic and ABAQUS.The models were composed of bony vertebrae, articulating facets, intervertebral disc and associated ligaments.The loads of moments 1.5Nm at different directions (flexion, extension, lateral bending and axial rotation)were applied at preoperative model to calculate intersegmental ranges of motion.The results were compared with the previous studies to verify the validation of the models. Results: Three-dimensional finite element models of the modified cervical single open- door laminoplasty had 102258 elements (preoperative model) and 161 892 elements (postoperative model) respectively, including C(2-7) six bony vertebraes, C(2-3)-C(6-7) five intervertebral disc, main ligaments and lateral mass screws.The intersegmental responses at the preoperative model under the loads of moments 1.5 Nm at different directions were similar to the previous published data. Conclusion: Three-dimensional finite element models of the modified cervical single open- door laminoplasty were successfully established and had a good biological fidelity, which can be used for further study.

Commutation circuit for an HVDC circuit breaker

DOEpatents

Premerlani, William J.

1981-01-01

A commutation circuit for a high voltage DC circuit breaker incorporates a resistor capacitor combination and a charging circuit connected to the main breaker, such that a commutating capacitor is discharged in opposition to the load current to force the current in an arc after breaker opening to zero to facilitate arc interruption. In a particular embodiment, a normally open commutating circuit is connected across the contacts of a main DC circuit breaker to absorb the inductive system energy trapped by breaker opening and to limit recovery voltages to a level tolerable by the commutating circuit components.

Commutation circuit for an HVDC circuit breaker

DOEpatents

Premerlani, W.J.

1981-11-10

A commutation circuit for a high voltage DC circuit breaker incorporates a resistor capacitor combination and a charging circuit connected to the main breaker, such that a commutating capacitor is discharged in opposition to the load current to force the current in an arc after breaker opening to zero to facilitate arc interruption. In a particular embodiment, a normally open commutating circuit is connected across the contacts of a main DC circuit breaker to absorb the inductive system energy trapped by breaker opening and to limit recovery voltages to a level tolerable by the commutating circuit components. 13 figs.

Fabrication and characterization of a piezoelectric energy harvester with clamped-clamped beams

NASA Astrophysics Data System (ADS)

Cui, Yan; Yu, Menglin; Gao, Shiqiao; Kong, Xiangxin; Gu, Wang; Zhang, Ran; Liu, Bowen

2018-05-01

This work presents a piezoelectric energy harvester with clamped-clamped beams, and it is fabricated with MEMS process. When excited by sinusoidal vibration, the energy harvester has a sharp jumping down phenomenon and the measured frequency responses of the clamped-clamped beams structure show a larger bandwidth which is about 56Hz, more efficient than that with cantilever beams. When the exciting acceleration ac is 12m/s2, the energy harvester achieves to a maximum open-circuit voltage of 94mV on one beam. The load voltage is proportional to the load resistance, and it increased with the increase of load resistance. Connected four beams in series, the output power reaches the maximum value of 730 nW and the optimal load is 15KΩ to one beam.

Fast-acting valve actuator

DOEpatents

Cho, Nakwon

1980-01-01

A fast-acting valve actuator utilizes a spring driven pneumatically loaded piston to drive a valve gate. Rapid exhaust of pressurized gas from the pneumatically loaded side of the piston facilitates an extremely rapid piston stroke. A flexible selector diaphragm opens and closes an exhaust port in response to pressure differentials created by energizing and de-energizing a solenoid which controls the pneumatic input to the actuator as well as selectively providing a venting action to one side of the selector diaphragm.

Development of an Open Building Automation System Specification Based on ANSI/ASHRAE 135-2004 (BACnet(R) Communications Protocol: A Technical Assessment

DTIC Science & Technology

2007-02-01

on/off control), trending and trend reports, load shedding/load manage- ment, remote setpoint adjustment, initial diagnosis of a service call and...building-specific operational data such as on/off scheduling com- mands, setpoints , and outside air temperature. With help from several other agencies and...interface for monitoring 3. Provide one interface for device/system management/configuration 4. ( Optimally ) provide one interface for device

Development of an Open Building Automation System Specification Based on ANSI/ASHRAE 135-2004 (BACnet(Registered) Communications Protocol): A Technical Assessment

DTIC Science & Technology

2007-02-01

on/off control), trending and trend reports, load shedding/load manage- ment, remote setpoint adjustment, initial diagnosis of a service call and...building-specific operational data such as on/off scheduling com- mands, setpoints , and outside air temperature. With help from several other agencies and...interface for monitoring 3. Provide one interface for device/system management/configuration 4. ( Optimally ) provide one interface for device

Corrosion-Fatigue Cracking in HY-80 and HY-130 Steels

DTIC Science & Technology

2015-01-22

Naval Research Laboratory Washington, DC 20375-5320 NRL/MR/6355--15-9584 Corrosion- Fatigue Cracking in HY-80 and HY-130 Steels January 22, 2015 P.S...RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (include area code) b. ABSTRACT c. THIS PAGE 18. NUMBER OF PAGES 17. LIMITATION OF ABSTRACT Corrosion- Fatigue ...including [NaCl] concentration) and load ratio on fatigue crack growth kinetics of HY-80 and HY-130 steels. Fracture mechanics wedge-opening-load

High Rate Lithium-Thionyl Chloride Battery Development for Undersea Weapon Propulsion Applications. Revised.

DTIC Science & Technology

1978-08-23

dislodged only a fraction of the SAB. According to FMI, thinner, more open grades of vitreous carbon paper would permit higher loading of SAB...bonded carbon fiber, porous silver and porous nickel cathodes were dis- charged in test cells. All polarized immediately below 2. 7 volts at 52 mA/cm2...Increased electrolyte molarity delivered a modest increase in run time but resulted -_ in somewhat lower load voltage plateaus. - As before, carbon fiber

Joint Loads and Cartilage Stress in Intact Joints of Military Transtibial Amputees: Enhancing Quality of Life

DTIC Science & Technology

2017-04-01

crosstalk); analysis of tested subjects underway. 4) Developed analytical methods to obtain knee joint loads using EMG-driven inverse dynamics; analysis of...13/2018. Completion %: 40. Task 1.3: EMG-driven inverse dynamic (ID) analyses with OpenSim for amputee and control group subjects. Target date: 1...predicted by EMG-driven inverse dynamics. Two-three conference papers are being prepared for submission in February 2017. Other achievements. None

An optimal design of magnetostrictive material (MsM) based energy harvester

NASA Astrophysics Data System (ADS)

Hu, Jingzhen; Yuan, Fuh-Gwo; Xu, Fujun; Huang, Alex Q.

2010-04-01

In this study, an optimal vibration-based energy harvesting system using magnetostrictive material (MsM) has been designed to power the Wireless Intelligent Sensor Platform (WISP), developed at North Carolina State University. A linear MsM energy harvesting device has been modeled and optimized to maximize the power output. The effects of number of MsM layers and glue layers, and load matching on the output power of the MsM energy harvester have been analyzed. From the measurement, the open circuit voltage can reach 1.5 V when the MsM cantilever beam operates at the 2nd natural frequency 324 Hz. The AC output power is 0.97 mW, giving power density 279 μW/cm3. Since the MsM device has low open circuit output voltage characteristics, a full-wave quadrupler has been designed to boost the rectified output voltage. To deliver the maximum output power to the load, a complex conjugate impedance matching between the load and the MsM device has been implemented using a discontinuous conduction mode (DCM) buck-boost converter. The maximum output power after the voltage quadrupler is now 705 μW and power density reduces to 202.4 μW/cm3, which is comparable to the piezoelectric energy harvesters given in the literature. The output power delivered to a lithium rechargeable battery is around 630 μW, independent of the load resistance.

KSC-99pp1182

NASA Image and Video Library

1999-10-07

KENNEDY SPACE CENTER, FLA. -- At KSC's Shuttle Landing Facility, NASA's Super Guppy opens to reveal its cargo, the International Space Station's (ISS) S1 truss. Manufactured by the Boeing Co. in Huntington Beach, Calif., this component of the ISS is the first starboard (right-side) truss segment, whose main job is providing structural support for the orbiting research facility's radiator panels that cool the Space Station's complex power system. The S1 truss segment also will house communications systems, external experiment positions and other subsystems. Primarily constructed of aluminum, the truss segment is 45 feet long, 15 feet wide and 6 feet tall. When fully outfitted, it will weigh 31,137 pounds. The truss is slated for flight in 2001. The Super Guppy, with its 25-foot diameter fuselage designed to handle oversized loads, is well prepared to transport the truss and other ISS segments. Loading the Guppy is easy because of the unique "fold-away" nose of the aircraft that opens 110 degrees for cargo loading. A system of rails in the cargo compartment, used with either Guppy pallets or fixtures designed for specific cargo, makes cargo loading simple and efficient. Rollers mounted in the rails allow pallets or fixtures to be moved by an electric winch mounted beneath the cargo floor. Automatic hydraulic lock pins in each rail secure the pallet for flight. The truss is to be transferred to the Operations and Checkout Building

Numerical optimization of open-porous bone scaffold structures to match the elastic properties of human cortical bone.

PubMed

Wieding, Jan; Wolf, Andreas; Bader, Rainer

2014-09-01

Treatment of large segmental bone defects, especially in load bearing areas, is a complex procedure in orthopedic surgery. The usage of additive manufacturing processes enables the creation of customized bone implants with arbitrary open-porous structure satisfying both the mechanical and the biological requirements for a sufficient bone ingrowth. Aim of the present numerical study was to optimize the geometrical parameters of open-porous titanium scaffolds to match the elastic properties of human cortical bone with respect to an adequate pore size. Three different scaffold designs (cubic, diagonal and pyramidal) were numerically investigated by using an optimization approach. Beam elements were used to create the lattice structures of the scaffolds. The design parameters strut diameter and pore size ranged from 0.2 to 1.5mm and from 0 to 3.0mm, respectively. In a first optimization step, the geometrical parameters were varied under uniaxial compression to obtain a structural modulus of 15GPa (Young׳s modulus of cortical bone) and a pore size of 800µm was aimed to enable cell ingrowth. Furthermore, the mechanical behavior of the optimized structures under bending and torsion was investigated. Results for bending modulus were between 9.0 and 14.5GPa. In contrast, shear modulus was lowest for cubic and pyramidal design of approximately 1GPa. Here, the diagonal design revealed a modulus of nearly 20GPa. In a second step, large-sized bone scaffolds were created and placed in a biomechanical loading situation within a 30mm segmental femoral defect, stabilized with an osteosynthesis plate and loaded with physiological muscle forces. Strut diameter for the 17 sections of each scaffold was optimized independently in order to match the biomechanical stability of intact bone. For each design, highest strut diameter was found at the dorsal/medial site of the defect and smallest strut diameter in the center. In conclusion, we demonstrated the possibility of providing optimized open-porous scaffolds for bone regeneration by considering both mechanical and biological aspects. Furthermore, the results revealed the need of the investigation and comparison of different load scenarios (compression, bending and torsion) as well as complex biomechanical loading for a profound characterization of different scaffold designs. The usage of a numerical optimization process was proven to be a feasible tool to reduce the amount of the required titanium material without influencing the biomechanical performance of the scaffold negatively. By using fully parameterized models, the optimization approach is adaptable to other scaffold designs and bone defect situations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural response of nuclear containment shield buildings with unanticipated construction openings

NASA Astrophysics Data System (ADS)

Mac Namara, Sinead Caitriona

As Nuclear Power Plants age many require steam generator replacement. There is a nickel alloy in the steam generator tubes that is susceptible to stress cracking and although these cracks can be sealed the generator becomes uneconomical without 10%-15% of the tubes. The steam generator in a typical nuclear power plant is housed in the containment structure next to the reactor. The equipment hatch is not big enough to facilitate steam generator replacement, thus construction openings in the dome of the containment structure are required. To date the structural consequences of construction openings in the dome have not been examined. This thesis examines the effects of such openings. The prototype concrete dome is made up of a 2 ft thick dome atop 3 ft thick and 170 ft high cylindrical walls (radius 65.5 ft) with a tension ring 15 ft high and 8 ft thick in between. The dome of the building is cast in two layers; a lower 9 inch layer that serves as the formwork for an upper 15 inch layer. The weight of the dome is carried in axial compression along the hoops and meridians of the dome. The first finite element model uses shell elements and considers two limiting load cases; where the two layers act as one, and where the lower layer carries the weight of both. The openings interrupt the hoops and meridians and the weight of the dome must be redistributed around the openings. Without openings, the stresses due to dead load in the structure are very low when compared to the material strength. The impact of the openings is increased compression stresses near the opening. The maximum stresses are approximately four times larger than in the original structure. These results are confirmed by the second model which is made from layers of solid elements. This model shows a significant difference between the compression on the top surface of the dome, in the affected areas, and that on the bottom surface, leading to shear stresses. These shear stresses are largest around the opening but are not large enough to cause delamination.

The effects of bird use on nutrient removal in a constructed wastewater-treatment wetland

USGS Publications Warehouse

Andersen, D.C.; Sartoris, J.J.; Thullen, J.S.; Reusch, P.G.

2003-01-01

A 9.9-ha constructed wetland designed to reduce nitrogen in municipal wastewater following conventional secondary treatment began operating in southern California's San Jacinto Valley in September 1994. The wetland incorporated zones of bulrush (Schoenoplectus acutus and S. californicus) for effluent treatment, plus areas of 1.8-m deep open water and other features to benefit wintering waterfowl. A one-year long program to monitor bird use and evaluate their contribution to loadings of nitrogen and phosphorus was initiated seven months later and a second, four-month long period of monitoring was initiated after a 20-month hiatus. Daily bird use peaked at nearly 12,000 individuals during the second period. Estimates of maximum daily nitrogen and phosphorus input by birds were 139 g N ha−1 day−1 and 56 g P ha−1 day−1. Following a reconfiguration of the wetland that increased the area of open water, a third year-long period of monitoring was initiated in September 2000. Estimated maximum daily loading attributable to birds during this period reached 312 g N ha−1 day−1 and 124 g P ha−1 day−1. These levels represent only 2.6% and 7.0%, respectively, of the mean daily loads of N and P in inflow water from the wastewater-treatment plant. Wintering waterfowl contributed the most to nutrient loading, but the numerically dominant species was the colonial Red-winged Blackbird (Agelaius phoeniceus). The wetland's nutrient-removal efficiency was negatively correlated to bird loading. However, the greatest bird loading occurred during November to March, when winter conditions would reduce microbial nutrient-removal processes and plant uptake in the wetland. Multiple regression analysis indicated that variation in nutrient removal efficiency over a one-year period was best explained by wetland water temperature (R2 = 0.21) and that little additional insight was gained by adding bird loading and inflow nutrient load data (R2 = 0.22). This case study supports the concept that a constructed wetland can be designed both to reduce nutrients in municipal wastewater and to provide habitat for wetland birds.

Refilling of carbon nanotube cartridges for 3D nanomanufacturing

NASA Astrophysics Data System (ADS)

Bekarevich, Raman; Toyoda, Masami; Baba, Shuichi; Nakata, Toshihiko; Hirahara, Kaori

2016-03-01

Metal-filled carbon nanotubes (CNTs) are known to be used as pen-tip injectors for 3D manufacturing on the nanoscale. However, the CNT interior cannot accumulate enough material to fabricate complex metallic nanostructures. Therefore a method for refilling the CNT cartridge needs to be developed. The strategy for refilling of CNT cartridges is suggested in this study. Controlled growth of gold nanowires in the interior of isolated CNTs using a real-time manipulator installed in a transmission electron microscope is reported herein. The encapsulation process of discrete gold nanoparticles in the hollow spaces of open-ended multi-wall CNTs was evaluated in detail. The experimental results reveal that the serial loading of isolated gold nanoparticles allows the control of the length of the loaded nanowires with nanometer accuracy. Thermophoresis and the coalescence of gold nanoparticles are assumed to be the primary mechanisms responsible for gold loading into a CNT cartridge.Metal-filled carbon nanotubes (CNTs) are known to be used as pen-tip injectors for 3D manufacturing on the nanoscale. However, the CNT interior cannot accumulate enough material to fabricate complex metallic nanostructures. Therefore a method for refilling the CNT cartridge needs to be developed. The strategy for refilling of CNT cartridges is suggested in this study. Controlled growth of gold nanowires in the interior of isolated CNTs using a real-time manipulator installed in a transmission electron microscope is reported herein. The encapsulation process of discrete gold nanoparticles in the hollow spaces of open-ended multi-wall CNTs was evaluated in detail. The experimental results reveal that the serial loading of isolated gold nanoparticles allows the control of the length of the loaded nanowires with nanometer accuracy. Thermophoresis and the coalescence of gold nanoparticles are assumed to be the primary mechanisms responsible for gold loading into a CNT cartridge. Electronic supplementary information (ESI) available: Variations of loading of the initial nanoparticle into the CNT, movies demonstrating the processes of the loading of the initial nanoparticle and elongation of encapsulated nanowire. See DOI: 10.1039/c5nr08712k

Antitumor effects of hydroxycamptothecin-loaded poly[ethylene glycol]-poly [gamma-benzyl-L-glutamate] micelles against oral squamous cell carcinoma.

PubMed

Ding, Xue-Qiang; Chen, Dan; Wang, An-Xun; Li, Su; Chen, Yu; Wang, Ji

2007-01-01

Therapeutic use of hydroxycamptothecin (HCPT), a promising antitumor agent, is limited by its poor solubility and rapid destruction. Amphiphilic block copolymer micelle carriers possess significant potential for improving drug solubility and stability. Poly[ethylene glycol]-poly[gamma-benzyl-L-glutamate] (PEG-PBLG) micelles were prepared and loaded with the active lactone form of HCPT using an uncomplicated dialysis method. HPLC and scanning electron microscopy studies revealed an encapsulation efficiency of 56.8% and a core-shell figure with a mean diameter of 200 nm. Encapsulated HCPT lactone was compared with the less active, open ring-carboxylated HCPT-Na+ soluble form generated in vivo from the free active lactone for activity against oral squamous cell carcinoma. Cytotoxicity in vitro was measured in cultured Tca8113 cells by the MTT assay and microscopy techniques. The golden hamster cheek pouch squamous cell carcinoma model was employed for in vivo studies; encapsulated lactone and open ring-carboxylated forms of HCPT were administered intraperitoneally, followed by determinations of tumor growth rate and inhibition ratio. PEG-PBLG micelles were not cytotoxic in vitro. At 48 h of treatment, open ring-carboxylated HCPT proved significantly more cytotoxic in vitro than encapsulated HCPT lactone. At 96 h, however, the open ring-carboxylated and encapsulated drugs displayed comparable in vitro cytotoxicities. In the in vivo squamous cell carcinoma model, encapsulated HCPT lactone produced greater and more prolonged tumor suppression compared to the open ring-carboxylated form. The antitumor effects of HCPT/PEG-PBLG micelles against oral squamous cell carcinoma in vivo are concluded to be superior to those exerted by open ring-carboxylated HCPT.

Civil commitment as a "street-level" bureaucracy: case-load, professionalization and administration.

PubMed

Wunsch, J S; Teply, L L; Zimmerman, J; Peters, G W

1981-01-01

This article applies street-level bureaucracy theories to "coping" patterns of behavior that developed in an involuntary commitment system. Daily procedures and routines of five Nebraska county boards of mental health and the attitudes of their members were studied. The results showed that the urban, high case-load, professionally-oriented board informally modified statutory procedures significantly to reduce face-to-face client contact, limit the scope of its decisions, and displace responsibility for the most ambiguous decisions to the treatment facility and board psychiatrist. Rural, low case-load, less professionally-specialized boards also modified the statutory procedures, but conducted the commitment process in a far more ambiguous, open-ended, and tense system with substantial face-to-face client contact. Both urban and rural boards had multifaceted role definitions; rural boards, however, had a more open-ended perception of their functions, and attempted more actively to modify antisocial behavior and redirect board subjects to sources of social counseling. Therefore, understanding street-level "coping" behavior in an actual commitment context is important to develop realistic changes in civil commitment systems and to preclude informal procedures that reduce a commitment system's effectiveness or undermine a proposed patient' s rights.

Experimental Study on Fatigue Behaviour of Shot-Peened Open-Hole Steel Plates

PubMed Central

Wang, Zhi-Yu; Wang, Qing-Yuan; Cao, Mengqin

2017-01-01

This paper presents an experimental study on the fatigue behaviour of shot-peened open-hole plates with Q345 steel. The beneficial effects induced by shot peening on the fatigue life improvement are highlighted. The characteristic fatigue crack initiation and propagation modes of open-hole details under fatigue loading are revealed. The surface hardening effect brought by the shot peening is analyzed from the aspects of in-depth micro-hardness and compressive residual stress. The fatigue life results are evaluated and related design suggestions are made as a comparison with codified detail categories. In particular, a fracture mechanics theory-based method is proposed and demonstrated its validity in predicting the fatigue life of studied shot-peened open-hole details. PMID:28841160

An Open Source Simulation System

NASA Technical Reports Server (NTRS)

Slack, Thomas

2005-01-01

An investigation into the current state of the art of open source real time programming practices. This document includes what technologies are available, how easy is it to obtain, configure, and use them, and some performance measures done on the different systems. A matrix of vendors and their products is included as part of this investigation, but this is not an exhaustive list, and represents only a snapshot of time in a field that is changing rapidly. Specifically, there are three approaches investigated: 1. Completely open source on generic hardware, downloaded from the net. 2. Open source packaged by a vender and provided as free evaluation copy. 3. Proprietary hardware with pre-loaded proprietary source available software provided by the vender as for our evaluation.

Compliance measurements of chevron notched four point bend specimen

NASA Technical Reports Server (NTRS)

Calomino, Anthony; Bubsey, Raymond; Ghosn, Louis J.

1994-01-01

The experimental stress intensity factors for various chevron notched four point bend specimens are presented. The experimental compliance is verified using the analytical solution for a straight through crack four point bend specimen and the boundary integral equation method for one chevron geometry. Excellent agreement is obtained between the experimental and analytical results. In this report, stress intensity factors, loading displacements and crack mouth opening displacements are reported for different crack lengths and different chevron geometries, under four point bend loading condition.

Invariant-Based Inverse Engineering of Crane Control Parameters

NASA Astrophysics Data System (ADS)

González-Resines, S.; Guéry-Odelin, D.; Tobalina, A.; Lizuain, I.; Torrontegui, E.; Muga, J. G.

2017-11-01

By applying invariant-based inverse engineering in the small-oscillation regime, we design the time dependence of the control parameters of an overhead crane (trolley displacement and rope length) to transport a load between two positions at different heights with minimal final-energy excitation for a microcanonical ensemble of initial conditions. The analogy between ion transport in multisegmented traps or neutral-atom transport in moving optical lattices and load manipulation by cranes opens a route for a useful transfer of techniques among very different fields.

Investigation of New Semiinsulating Behavior of III-V Compounds.

DTIC Science & Technology

1990-02-23

load (I 10) directions, respectively. Open circles correspond to p-type samples cell . The sample with the length Io of 7 mm, was placed deformed in the...DISCUSSION at a constant rate dl /dt of 0.05 mm/min. The load cell was used to monitor the applied force. All samples used in this A. Free-carrier...the growth of epitaxial quality GaAs bulk crystals (Bryskiewicz et al 1987b). A schematic diagram of the growth cell used in our growth experi- S-nts

Advanced Flaw Manufacturing and Crack Growth Control

NASA Astrophysics Data System (ADS)

Kemppainen, M.; Pitkänen, J.; Virkkunen, I.; Hänninen, H.

2004-02-01

Advanced artificial flaw manufacturing method has become available. The method produces true fatigue cracks, which are representative of most service-induced cracks. These cracks can be used to simulate behaviour of realistic cracks under service conditions. This paper introduces studies of the effects of different thermal loading cycles to crack opening and residual stress state as seen at the surface of the sample and in the ultrasonic signal. In-situ measurements were performed under dynamic thermal fatigue loading of a 20 mm long artificial crack.

Method and apparatus for rapid stopping and starting of a thermoacoustic engine

DOEpatents

Swift, Gregory W.; Backhaus, Scott N.; Gardner, David L.

2003-11-11

A thermoacoustic engine-driven system with a hot heat exchanger, a regenerator or stack, and an ambient heat exchanger includes a side branch load for rapid stopping and starting, the side branch load being attached to a location in the thermoacoustic system having a nonzero oscillating pressure and comprising a valve, a flow resistor, and a tank connected in series. The system is rapidly stopped simply by opening the valve and rapidly started by closing the valve.

40 CFR 52.876 - Compliance schedules.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., 1974. Continental Grain Co., rail car loading Hutchinson 28-19-50 Aug. 15, 1974. Far-Mar-Co, Inc... & Foundry, cupola Wichita 28-19-20A, 28-19-50A Oct. 4, 1974. Kansas Army Ammunition Plant, open burning...

Controlled release of chlorhexidine antiseptic from microporous amorphous silica applied in open porosity of an implant surface.

PubMed

Verraedt, Els; Braem, Annabel; Chaudhari, Amol; Thevissen, Karin; Adams, Erwin; Van Mellaert, Lieve; Cammue, Bruno P A; Duyck, Joke; Anné, Jozef; Vleugels, Jef; Martens, Johan A

2011-10-31

Amorphous microporous silica (AMS) serving as a reservoir for controlled release of a bioactive agent was applied in the open porosity of a titanium coating on a Ti-6Al-4V metal substrate. The pores of the AMS emptied by calcination were loaded with chlorhexidine diacetate (CHX) via incipient wetness impregnation with CHX solution, followed by solvent evaporation. Using this CHX loaded AMS system on titanium substrate sustained release of CHX into physiological medium was obtained over a 10 day-period. CHX released from the AMS coating was demonstrated to be effective in killing planktonic cultures of the human pathogens Candida albicans and Staphylococcus epidermidis. This surface modification of titanium bodies with AMS controlled release functionality for a bioactive compound potentially can be applied on dental and orthopaedic implants to abate implant-associated microbial infection. Copyright © 2011 Elsevier B.V. All rights reserved.

Definition of mutually optimum NDI and proof test criteria for 2219 aluminum pressure vessels. Volume 1: Methods

NASA Technical Reports Server (NTRS)

Schwartzberg, F. R.; King, R. G.; Todd, P. H., Jr.

1979-01-01

The requirements for proof testing and nondestructive inspection of aluminum pressure vessels were discussed. The following conclusions are (1) lack-of-fusion weld defects are sufficiently tight in the as-welded condition to be considered undetectable; (2) proof-level loads are required to fully open lack-of-fusion weld defects; (3) significant crack opening occurs at subproof levels so that an inspection enhancement loading treatment designed to avoid catastrophic failure is feasible; (4) currently used proof levels for 2219 pressure vessels are adequate for postproof inspection; (5) quantification of defect size and location using collimated ultrasonic pitch-catch techniques appears sufficiently feasible for tankage to warrant developmental work; (6) for short-time single-cycle pressure-vessel applications, postproof inspection is desirable; and (7) for long-term multiple-cycle pressure-vessel applications, postproof inspection is essential for life assurance.

Transparent and Self-Supporting Graphene Films with Wrinkled- Graphene-Wall-Assembled Opening Polyhedron Building Blocks for High Performance Flexible/Transparent Supercapacitors.

PubMed

Li, Na; Huang, Xuankai; Zhang, Haiyan; Li, Yunyong; Wang, Chengxin

2017-03-22

Improving mass loading while maintaining high transparency and large surface area in one self-supporting graphene film is still a challenge. Unfortunately, all of these factors are absolutely essential for enhancing the energy storage performance of transparent supercapacitors for practical applications. To solve the above bottleneck problem, we produce a novel self-supporting flexible and transparent graphene film (STF-GF) with wrinkled-wall-assembled opened-hollow polyhedron building units. Taking advantage of the microscopic morphology, the STF-GF exhibits improved mass loading with high transmittance (70.2% at 550 nm), a large surface area (1105.6 m 2 /g), and good electrochemical performance: high energy (552.3 μWh/cm 3 ), power densities (561.9 mW/cm 3 ), a superlong cycle life, and good cycling stability (the capacitance retention is ∼94.8% after 20,000 cycles).

Fast Response, Open-Celled Porous, Shape Memory Effect Actuators with Integrated Attachments

NASA Technical Reports Server (NTRS)

Jardine, Andrew Peter (Inventor)

2015-01-01

This invention relates to the exploitation of porous foam articles exhibiting the Shape Memory Effect as actuators. Each foam article is composed of a plurality of geometric shapes, such that some geometric shapes can fit snugly into or around rigid mating connectors that attach the Shape Memory foam article intimately into the load path between a static structure and a moveable structure. The foam is open-celled, composed of a plurality of interconnected struts whose mean diameter can vary from approximately 50 to 500 microns. Gases and fluids flowing through the foam transfer heat rapidly with the struts, providing rapid Shape Memory Effect transformations. Embodiments of porous foam articles as torsional actuators and approximately planar structures are disposed. Simple, integral connection systems exploiting the ability to supply large loads to a structure, and that can also supply hot and cold gases and fluids to effect rapid actuation are also disposed.

Evolution of Large-Scale Magnetic Fields and State Transitions in Black Hole X-Ray Binaries

NASA Astrophysics Data System (ADS)

Wang, Ding-Xiong; Huang, Chang-Yin; Wang, Jiu-Zhou

2010-04-01

The state transitions of black hole (BH) X-ray binaries are discussed based on the evolution of large-scale magnetic fields, in which the combination of three energy mechanisms are involved: (1) the Blandford-Znajek (BZ) process related to the open field lines connecting a rotating BH with remote astrophysical loads, (2) the magnetic coupling (MC) process related to the closed field lines connecting the BH with its surrounding accretion disk, and (3) the Blandford-Payne (BP) process related to the open field lines connecting the disk with remote astrophysical loads. It turns out that each spectral state of the BH binaries corresponds to each configuration of magnetic field in BH magnetosphere, and the main characteristics of low/hard (LH) state, hard intermediate (HIM) state and steep power law (SPL) state are roughly fitted based on the evolution of large-scale magnetic fields associated with disk accretion.

An analytical investigation of the performance of solar collectors as nighttime heat radiators in airconditioning cycles

NASA Technical Reports Server (NTRS)

Jones, C. B.; Smetana, F. O.

1979-01-01

It was found that if the upper and lower ends of a collector were opened, large free convention currents may be set up between the collector surface and the cover glass(es) which can result in appreciable heat rejection. If the collector is so designed that both plates surfaces are exposed to convection currents when the upper and lower ends of the collector enclosure are opened, the heat rejection rate is 300 watts sq m when the plate is 13 C above ambient. This is sufficient to permit a collector array designed to provide 100 percent of the heating needs of a home to reject the accumulated daily air conditioning load during the course of a summer night. This also permits the overall energy requirements for cooling to be reduced by at least 15 percent and shift the load on the utility entirely to the nighttime hours.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S. Y.; Choo, Hahn; Liaw, Peter K

The combined effects of overload-induced enlarged compressive residual stresses and crack tip blunting with secondary cracks are suggested to be responsible for the observed changes in the crack opening load and resultant post-overload transient crack growth behavior [Lee SY, Liaw PK, Choo H, Rogge RB, Acta Mater 2010;59:485-94]. In this article, in situ neutron diffraction experiments were performed to quantify the influence of the combined effects by investigating the internal-stress evolution at various locations away from the crack tip. In the overload-retardation period, stress concentration occurs in the crack blunting region (an overload point) until a maximum crack arrest loadmore » is reached. The stress concentration is then transferred from the blunting region to the propagating crack tip (following the overload), requiring a higher applied load, as the closed crack is gradually opened. The transfer phenomena of the stress concentration associated with a crack opening process account for the nonlinearity of strain response in the vicinity of the crack tip. The delaying action of stress concentration at the crack tip is understood in conjunction with the concept of a critical stress (i.e. the stress required to open the closed crack behind the crack tip). A linear relationship between {Delta}{var_epsilon}{sub eff} and {Delta}K{sub eff} provides experimental support for the hypothesis that {Delta}K{sub eff} can be considered as the fatigue crack tip driving force.« less

Stress intensity factors and COD in an orthotropic strip

NASA Technical Reports Server (NTRS)

Kaya, A. C.; Erdogan, F.

1980-01-01

The elasticity problem for an orthotropic strip or a beam with an internal or an edge crack under general loading conditions is considered. The numerical results are given for four basic loading conditions, namely, uniform tension, pure bending, three point bending, and concentrated surface shear loading. For the strip with an edge crack additional results regarding the crack opening displacements are obtained by using the plastic strip model. A critical quantity which is tabulated is the maximum compressive stress in the plane of the crack. It is shown that this stress may easily exceed the yield limit in compression and hence may severely limit the range of application of the plasticity results.

A novel strategy for load balancing of distributed medical applications.

PubMed

Logeswaran, Rajasvaran; Chen, Li-Choo

2012-04-01

Current trends in medicine, specifically in the electronic handling of medical applications, ranging from digital imaging, paperless hospital administration and electronic medical records, telemedicine, to computer-aided diagnosis, creates a burden on the network. Distributed Service Architectures, such as Intelligent Network (IN), Telecommunication Information Networking Architecture (TINA) and Open Service Access (OSA), are able to meet this new challenge. Distribution enables computational tasks to be spread among multiple processors; hence, performance is an important issue. This paper proposes a novel approach in load balancing, the Random Sender Initiated Algorithm, for distribution of tasks among several nodes sharing the same computational object (CO) instances in Distributed Service Architectures. Simulations illustrate that the proposed algorithm produces better network performance than the benchmark load balancing algorithms-the Random Node Selection Algorithm and the Shortest Queue Algorithm, especially under medium and heavily loaded conditions.

LOADING DEVICE

DOEpatents

Ohlinger, L.A.

1958-10-01

A device is presented for loading or charging bodies of fissionable material into a reactor. This device consists of a car, mounted on tracks, into which the fissionable materials may be placed at a remote area, transported to the reactor, and inserted without danger to the operating personnel. The car has mounted on it a heavily shielded magazine for holding a number of the radioactive bodies. The magazine is of a U-shaped configuration and is inclined to the horizontal plane, with a cap covering the elevated open end, and a remotely operated plunger at the lower, closed end. After the fissionable bodies are loaded in the magazine and transported to the reactor, the plunger inserts the body at the lower end of the magazine into the reactor, then is withdrawn, thereby allowing gravity to roll the remaining bodies into position for successive loading in a similar manner.

Autonomous grain combine control system

DOEpatents

Hoskinson, Reed L.; Kenney, Kevin L.; Lucas, James R.; Prickel, Marvin A.

2013-06-25

A system for controlling a grain combine having a rotor/cylinder, a sieve, a fan, a concave, a feeder, a header, an engine, and a control system. The feeder of the grain combine is engaged and the header is lowered. A separator loss target, engine load target, and a sieve loss target are selected. Grain is harvested with the lowered header passing the grain through the engaged feeder. Separator loss, sieve loss, engine load and ground speed of the grain combine are continuously monitored during the harvesting. If the monitored separator loss exceeds the selected separator loss target, the speed of the rotor/cylinder, the concave setting, the engine load target, or a combination thereof is adjusted. If the monitored sieve loss exceeds the selected sieve loss target, the speed of the fan, the size of the sieve openings, or the engine load target is adjusted.

Numerical calibration of the stable poisson loaded specimen

NASA Technical Reports Server (NTRS)

Ghosn, Louis J.; Calomino, Anthony M.; Brewer, Dave N.

1992-01-01

An analytical calibration of the Stable Poisson Loaded (SPL) specimen is presented. The specimen configuration is similar to the ASTM E-561 compact-tension specimen with displacement controlled wedge loading used for R-Curve determination. The crack mouth opening displacements (CMOD's) are produced by the diametral expansion of an axially compressed cylindrical pin located in the wake of a machined notch. Due to the unusual loading configuration, a three-dimensional finite element analysis was performed with gap elements simulating the contact between the pin and specimen. In this report, stress intensity factors, CMOD's, and crack displacement profiles are reported for different crack lengths and different contacting conditions. It was concluded that the computed stress intensity factor decreases sharply with increasing crack length, thus making the SPL specimen configuration attractive for fracture testing of brittle, high modulus materials.

Analytical stress intensity solution for the Stable Poisson Loaded specimen

NASA Technical Reports Server (NTRS)

Ghosn, Louis J.; Calomino, Anthony M.; Brewer, David N.

1993-01-01

An analytical calibration of the Stable Poisson Loaded (SPL) specimen is presented. The specimen configuration is similar to the ASTM E-561 compact-tension specimen with displacement controlled wedge loading used for R-curve determination. The crack mouth opening displacements (CMODs) are produced by the diametral expansion of an axially compressed cylindrical pin located in the wake of a machined notch. Due to the unusual loading configuration, a three-dimensional finite element analysis was performed with gap elements simulating the contact between the pin and specimen. In this report, stress intensity factors, CMODs, and crack displacement profiles, are reported for different crack lengths and different contacting conditions. It was concluded that the computed stress intensity factor decreases sharply with increasing crack length thus making the SPL specimen configuration attractive for fracture testing of brittle, high modulus materials.

The impact of shoulder abduction loading on EMG-based intention detection of hand opening and closing after stroke.

PubMed

Lan, Yiyun; Yao, Jun; Dewald, Julius P A

2011-01-01

Many stroke patients are subject to limited hand functions in the paretic arm due to a significant loss of Corticospinal Tract (CST) fibers. A possible solution for this problem is to classify surface Electromyography (EMG) signals generated by hand movements and uses that to implement Functional Electrical Stimulation (FES). However, EMG usually presents an abnormal muscle coactivation pattern shown as increased coupling between muscles within and/or across joints after stroke. The resulting Abnormal Muscle Synergies (AMS) could make the classification more difficult in individuals with stroke, especially when attempting to use the hand together with other joints in the paretic arm. Therefore, this study is aimed at identifying the impact of AMS following stroke on EMG pattern recognition between two hand movements. In an effort to achieve this goal, 7 chronic hemiparetic chronic stroke subjects were recruited and asked to perform hand opening and closing movements at their paretic arm while being either fully supported by a virtual table or loaded with 25% of subject's maximum shoulder abduction force. During the execution of motor tasks EMG signals from the wrist flexors and extensors were simultaneously acquired. Our results showed that increased synergy-induced activity at elbow flexors, induced by increasing shoulder abduction loading, deteriorated the performance of EMG pattern recognition for hand opening for those with a weak grasp strength and EMG activity. However, no such impact on hand closing has yet been observed possibly because finger/wrist flexion is facilitated by the shoulder abduction-induced flexion synergy.

Natural leathers from natural materials: progressing toward a new arena in leather processing.

PubMed

Saravanabhavan, Subramani; Thanikaivelan, Palanisamy; Rao, Jonnalagadda Raghava; Nair, Balachandran Unni; Ramasami, Thirumalachari

2004-02-01

Globally, the leather industry is currently undergoing radical transformation due to pollution and discharge legislations. Thus, the leather industry is pressurized to look for cleaner options for processing the raw hides and skins. Conventional methods of pre-tanning, tanning and post-tanning processes are known to contribute more than 98% of the total pollution load from the leather processing. The conventional method of the tanning process involves the "do-undo" principle. Furthermore, the conventional methods employed in leather processing subject the skin/ hide to a wide variation in pH (2.8-13.0). This results in the emission of huge amounts of pollution loads such as BOD, COD, TDS, TS, sulfates, chlorides and chromium. In the approach illustrated here, the hair and flesh removal as well as fiber opening have been achieved using biocatalysts at pH 8.0, pickle-free natural tanning employing vegetable tannins, and post-tanning using environmentally friendly chemicals. Hence, this process involves dehairing, fiber opening, and pickle-free natural tanning followed by ecofriendly post-tanning. It has been found that the extent of hair removal and opening up of fiber bundles is comparable to that of conventionally processed leathers. This has been substantiated through scanning electron microscopic analysis and softness measurements. Performance of the leathers is shown to be on par with conventionally chrome-tanned leathers through physical and hand evaluation. The process also exhibits zero metal (chromium) discharge and significant reduction in BOD, COD, TDS, and TS loads by 83, 69, 96, and 96%, respectively. Furthermore, the developed process seems to be economically viable.

Inhibition of tracheal vascular extravasation by liposome-encapsulated albuterol in rats.

PubMed

Zhang, W; Guo, L; Nadel, J A; Papahadjopoulos, D

1998-03-01

To develop a liposome-based system for systemic delivery of anti-inflammatory drugs to airways and other inflamed tissues. Postcapillary venular gap junctions open during airway inflammation and allow fluid accumulation and permit molecules (e.g. complement, kininogen) to enter tissues, initiating inflammatory cascades. Beta-adrenergic agonists prevent inflammatory plasma extravasation, but because of their deleterious side effects, they are not used intravenously. When sterically stabilized "stealth" liposomes are injected i.v., they remain in the circulation for long periods. Inflammatory mediators [e.g., substance P(SP)] open postcapillary venular gaps and allow liposomes and their contents to be deposited selectively in the inflamed tissue. We hypothesized that liposomes encapsulating a beta-adrenergic agonist, such as albuterol, would deposit selectively in inflamed airway tissue, where the drug would slowly leak out of the liposomes, resulting in closure of the gaps, thus preventing subsequent inflammatory extravasation. To test this hypothesis, we delivered albuterol-loaded liposomes i.v. in rats. Then we injected SP to open the venular gaps and allow accumulation of the drug-loaded liposomes in airway tissue. We examined whether this treatment resulted in inhibition of subsequent plasma extravasation induced by SP. The results indicate that liposome-encapsulated albuterol inhibits subsequent extravasation, presumably by leaking out of liposomes in airway tissue. This inhibition occurs for prolonged periods of time and with limited side effects compared to the effect of free albuterol. We conclude that liposomes loaded with appropriate drugs, by migrating to inflamed tissue and subsequently inhibiting inflammatory cascades, may be of therapeutic value in inflammatory diseases.

Shooting and bouncing rays - Calculating the RCS of an arbitrarily shaped cavity

NASA Technical Reports Server (NTRS)

Ling, Hao; Chou, Ri-Chee; Lee, Shung-Wu

1989-01-01

A ray-shooting approach is presented for calculating the interior radar cross section (RCS) from a partially open cavity. In the problem considered, a dense grid of rays is launched into the cavity through the opening. The rays bounce from the cavity walls based on the laws of geometrical optics and eventually exit the cavity via the aperture. The ray-bouncing method is based on tracking a large number of rays launched into the cavity through the opening and determining the geometrical optics field associated with each ray by taking into consideration (1) the geometrical divergence factor, (2) polarization, and (3) material loading of the cavity walls. A physical optics scheme is then applied to compute the backscattered field from the exit rays. This method is so simple in concept that there is virtually no restriction on the shape or material loading of the cavity. Numerical results obtained by this method are compared with those for the modal analysis for a circular cylinder terminated by a PEC plate. RCS results for an S-bend circular cylinder generated on the Cray X-MP supercomputer show significant RCS reduction. Some of the limitations and possible extensions of this technique are discussed.

Implant-supported mandibular splinting affects temporomandibular joint biomechanics.

PubMed

Zaugg, Balthasar; Hämmerle, Christoph H F; Palla, Sandro; Gallo, Luigi M

2012-08-01

Mandibular functional movements lead to complex deformations of bony structures. The aim of this study was to test whether mandibular splinting influences condylar kinematics and temporomandibular joint (TMJ) loading patterns. Six subjects were analyzed by means of dynamic stereometry during jaw opening-closing with mandibles unconstrained as well as splinted transversally by a cast metal bar fixed bilaterally to two implant pairs in the (pre)molar region. Statistical analysis was performed by means of ANOVAs for repeated measurements (significance level α=0.05). Transversal splinting reduced mandibular deformation during jaw opening-closing as measured between two implants in the (pre)molar region on each side of the mandible significantly by 54%. Furthermore, splinting significantly reduced the distance between lateral condylar poles (average displacement vector magnitude of each pole: 0.84±0.36 mm; average mediolateral displacement component: 45±28% of the magnitude) and led to a medial displacement of their trajectories as well as a mediolateral displacement of stress-field paths. During jaw opening-closing, splinting of the mandible leads to a significant reduction of mandibular deformation and intercondylar distance and to altered stress-field paths, resulting in changed loading patterns of the TMJ structures. © 2011 John Wiley & Sons A/S.

Calcium Signaling in Taste Cells

PubMed Central

Medler, Kathryn F.

2014-01-01

The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. PMID:25450977

One-dimensional analysis of filamentary composite beam columns with thin-walled open sections

NASA Technical Reports Server (NTRS)

Lo, Patrick K.-L.; Johnson, Eric R.

1986-01-01

Vlasov's one-dimensional structural theory for thin-walled open section bars was originally developed and used for metallic elements. The theory was recently extended to laminated bars fabricated from advanced composite materials. The purpose of this research is to provide a study and assessment of the extended theory. The focus is on flexural and torsional-flexural buckling of thin-walled, open section, laminated composite columns. Buckling loads are computed from the theory using a linear bifurcation analysis and a geometrically nonlinear beam column analysis by the finite element method. Results from the analyses are compared to available test data.

29 CFR 1926.852 - Chutes.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (e) Any chute opening, into which workmen dump debris, shall be protected by a substantial guardrail approximately 42 inches above the floor or other surface on which the men stand to dump the material. Any space... of materials or debris loaded therein. ...

29 CFR 1926.852 - Chutes.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (e) Any chute opening, into which workmen dump debris, shall be protected by a substantial guardrail approximately 42 inches above the floor or other surface on which the men stand to dump the material. Any space... of materials or debris loaded therein. ...

29 CFR 1926.852 - Chutes.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... (e) Any chute opening, into which workmen dump debris, shall be protected by a substantial guardrail approximately 42 inches above the floor or other surface on which the men stand to dump the material. Any space... of materials or debris loaded therein. ...

Studies of air loads on man.

DOT National Transportation Integrated Search

1963-05-01

Data obtained in three different studies related to measurement of forces on the body due to air movement are summarized. The effects of short duration blast forces on personnel seated or standing at various distances from openings during pressure lo...

Field Investigation of a Strengthened Timber Trestle Railroad Bridge

DOT National Transportation Integrated Search

2003-06-01

A three-span, open-deck timber trestle railroad bridge had been previously field load tested. The prior testing program was done in cooperation with the Transportation Technology Center, Inc. a subsidiary of the Association of American Railroads. The...

29 CFR 1926.852 - Chutes.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (e) Any chute opening, into which workmen dump debris, shall be protected by a substantial guardrail approximately 42 inches above the floor or other surface on which the men stand to dump the material. Any space... of materials or debris loaded therein. ...

29 CFR 1926.852 - Chutes.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (e) Any chute opening, into which workmen dump debris, shall be protected by a substantial guardrail approximately 42 inches above the floor or other surface on which the men stand to dump the material. Any space... of materials or debris loaded therein. ...

Finite element analysis on the biomechanical stability of open porous titanium scaffolds for large segmental bone defects under physiological load conditions.

PubMed

Wieding, Jan; Souffrant, Robert; Mittelmeier, Wolfram; Bader, Rainer

2013-04-01

Repairing large segmental defects in long bones caused by fracture, tumour or infection is still a challenging problem in orthopaedic surgery. Artificial materials, i.e. titanium and its alloys performed well in clinical applications, are plenary available, and can be manufactured in a wide range of scaffold designs. Although the mechanical properties are determined, studies about the biomechanical behaviour under physiological loading conditions are rare. The goal of our numerical study was to determine the suitability of open-porous titanium scaffolds to act as bone scaffolds. Hence, the mechanical stability of fourteen different scaffold designs was characterized under both axial compression and biomechanical loading within a large segmental distal femoral defect of 30mm. This defect was stabilized with an osteosynthesis plate and physiological hip reaction forces as well as additional muscle forces were implemented to the femoral bone. Material properties of titanium scaffolds were evaluated from experimental testing. Scaffold porosity was varied between 64 and 80%. Furthermore, the amount of material was reduced up to 50%. Uniaxial compression testing revealed a structural modulus for the scaffolds between 3.5GPa and 19.1GPa depending on porosity and material consumption. The biomechanical testing showed defect gap alterations between 0.03mm and 0.22mm for the applied scaffolds and 0.09mm for the intact bone. Our results revealed that minimizing the amount of material of the inner core has a smaller influence than increasing the porosity when the scaffolds are loaded under biomechanical loading. Furthermore, an advanced scaffold design was found acting similar as the intact bone. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Calculation of Centrally Loaded Thin-Walled Columns Above the Buckling Limit

NASA Technical Reports Server (NTRS)

Reinitzhuber, F.

1945-01-01

When thin-walled columns formed from flanged sheet, such as used in airplane construction, are subjected to axial load, their behavior at failure varies according to the slenderness ratio. On long columns the axis deflects laterally while the cross section form is maintained; buckling results. The respective breaking load in the elastic range is computed by Euler's formula and for the plastic range by the Engesser- Karman formula. Its magnitude is essentially dependent upon the length. On intermediate length columns, especially where open sections are concerned, the cross section is distorted while the cross section form is preserved; twisting failure results. The buckling load in twisting is calculated according to Wagner and Kappus. On short columns the straight walls of low-bending resistance that form the column are deflected at the same time that the cross section form changes - buckling occurs without immediate failure. Then the buckling load of the total section computable from the buckling loads of the section walls is not the ultimate load; quite often, especially on thin-walled sections, it lies considerably higher and is secured by tests. Both loads, the buckling and the ultimate load are only in a small measure dependent upon length. The present report is an attempt to theoretically investigate the behavior of such short, thin-walled columns above the buckling load with the conventional calculating methods.

Evaluation of wheelchair sling seat and sling back crashworthiness.

PubMed

Ha, D; Bertocci, G; Karg, P; Deemer, E

2002-07-01

Many wheelchairs are used as vehicle seats by those who cannot transfer to a vehicle seat. Although ANSI/RESNA WC-19 has been recently adopted as a standard to evaluate crashworthiness of the wheelchairs used as motor vehicle seats, replacement or after-market seats may not be tested to this standard. This study evaluated the crashworthiness of two specimens each of three unique sling backs and three unique sling seats using a static test procedure intended to simulate crash loading conditions. To pass the test, a sling back is required to withstand a 2290 lb load, and a sling seat should be capable of withstanding a 3750 lb load. All, but two sling back specimens which failed at 1567 lb and 1787 lb, withstood the test criterion load. Two of six tested sling seats failed to pass the test: one failed at 3123 lb and the other failed to sustain the load for 5 s although it reached the test criterion load. Most of the failures occurred at the seams of the side openings of upholsteries where the wheelchair frame inserts for attachment.

Solar light-driven photocatalytic hydrogen evolution over ZnIn2S4 loaded with transition-metal sulfides

NASA Astrophysics Data System (ADS)

Shen, Shaohua; Chen, Xiaobo; Ren, Feng; Kronawitter, Coleman X.; Mao, Samuel S.; Guo, Liejin

2011-12-01

A series of Pt-loaded MS/ZnIn2S4 (MS = transition-metal sulfide: Ag2S, SnS, CoS, CuS, NiS, and MnS) photocatalysts was investigated to show various photocatalytic activities depending on different transition-metal sulfides. Thereinto, CoS, NiS, or MnS-loading lowered down the photocatalytic activity of ZnIn2S4, while Ag2S, SnS, or CuS loading enhanced the photocatalytic activity. After loading 1.0 wt.% CuS together with 1.0 wt.% Pt on ZnIn2S4, the activity for H2 evolution was increased by up to 1.6 times, compared to the ZnIn2S4 only loaded with 1.0 wt.% Pt. Here, transition-metal sulfides such as CuS, together with Pt, acted as the dual co-catalysts for the improved photocatalytic performance. This study indicated that the application of transition-metal sulfides as effective co-catalysts opened up a new way to design and prepare high-efficiency and low-cost photocatalysts for solar-hydrogen conversion.

Progressive collapse of a two-story reinforced concrete frame with embedded smart aggregates

NASA Astrophysics Data System (ADS)

Laskar, Arghadeep; Gu, Haichang; Mo, Y. L.; Song, Gangbing

2009-07-01

This paper reports the experimental and analytical results of a two-story reinforced concrete frame instrumented with innovative piezoceramic-based smart aggregates (SAs) and subjected to a monotonic lateral load up to failure. A finite element model of the frame is developed and analyzed using a computer program called Open system for earthquake engineering simulation (OpenSees). The finite element analysis (FEA) is used to predict the load-deformation curve as well as the development of plastic hinges in the frame. The load-deformation curve predicted from FEA matched well with the experimental results. The sequence of development of plastic hinges in the frame is also studied from the FEA results. The locations of the plastic hinges, as obtained from the analysis, were similar to those observed during the experiment. An SA-based approach is also proposed to evaluate the health status of the concrete frame and identify the development of plastic hinges during the loading procedure. The results of the FEA are used to validate the SA-based approach for detecting the locations and occurrence of the plastic hinges leading to the progressive collapse of the frame. The locations and sequential development of the plastic hinges obtained from the SA-based approach corresponds well with the FEA results. The proposed SA-based approach, thus validated using FEA and experimental results, has a great potential to be applied in the health monitoring of large-scale civil infrastructures.

Does task-irrelevant colour information create extraneous cognitive load? Evidence from a learning task.

PubMed

Miller, Paul; Hazan-Liran, Batel; Cohen, Danielle

2018-06-01

Previous studies have shown that task-irrelevant information impedes learning by creating extraneous cognitive load. But still open is whether such intrusion reflects a purely semantic phenomenon or whether it also stands for sheer perceptual interference. Using Cognitive Load Theory as a framework, this study aimed to answer this question by examining whether and how task-irrelevant colour information modifies extraneous cognitive load in relation to a new code-learning paradigm. For this purpose, university students were asked to learn, based on an example, associations between colour-related and colour-unrelated words and digits presented in black or in a mismatched ink colour. Evident costs in learning efficacy were found in learning the associations between words and digits for colour-related, but not for colour-unrelated, word stimuli. This suggests that interference by task-irrelevant information in learning stands for a mere semantic conflict. Implications of the findings for extraneous cognitive load on learning efficacy are discussed.

Biomechanical comparison of single-row arthroscopic rotator cuff repair technique versus transosseous repair technique.

PubMed

Tocci, Stephen L; Tashjian, Robert Z; Leventhal, Evan; Spenciner, David B; Green, Andrew; Fleming, Braden C

2008-01-01

This study determined the effect of tear size on gap formation of single-row simple-suture arthroscopic rotator cuff repair (ARCR) vs transosseous Mason-Allen suture open RCR (ORCR) in 13 pairs of human cadaveric shoulders. A massive tear was created in 6 pairs and a large tear in 7. Repairs were cyclically tested in low-load and high-load conditions, with no significant difference in gap formation. Under low-load, gapping was greater in massive tears. Under high-load, there was a trend toward increased gap with ARCR for large tears. All repairs of massive tears failed in high-load. Gapping was greater posteriorly in massive tears for both techniques. Gap formation of a modeled RCR depends upon the tear size. ARCR of larger tears may have higher failure rates than ORCR, and the posterior aspect appears to be the site of maximum gapping. Specific attention should be directed toward maximizing initial fixation of larger rotator cuff tears, especially at the posterior aspect.

Further Examination of the Vibratory Loads Reduction Results from the NASA/ARMY/MIT Active Twist Rotor Test

NASA Technical Reports Server (NTRS)

Wilbur, Matthew L.; Yeager, William T., Jr.; Sekula, Martin K.

2002-01-01

The vibration reduction capabilities of a model rotor system utilizing controlled, strain-induced blade twisting are examined. The model rotor blades, which utilize piezoelectric active fiber composite actuators, were tested in the NASA Langley Transonic Dynamics Tunnel using open-loop control to determine the effect of active-twist on rotor vibratory loads. The results of this testing have been encouraging, and have demonstrated that active-twist rotor designs offer the potential for significant load reductions in future helicopter rotor systems. Active twist control was found to use less than 1% of the power necessary to operate the rotor system and had a pronounced effect on both rotating- and fixed-system loads, offering reductions in individual harmonic loads of up to 100%. A review of the vibration reduction results obtained is presented, which includes a limited set of comparisons with results generated using the second-generation version of the Comprehensive Analytical Model of Rotorcraft Aerodynamics and Dynamics (CAMRAD II) rotorcraft comprehensive analysis.

Biophysical characterization of gold nanoparticles-loaded liposomes.

PubMed

Mady, Mohsen Mahmoud; Fathy, Mohamed Mahmoud; Youssef, Tareq; Khalil, Wafaa Mohamed

2012-10-01

Gold nanoparticles were prepared and loaded into the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposomes, named as gold-loaded liposomes. Biophysical characterization of gold-loaded liposomes was studied by transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy as well as turbidity and rheological measurements. FTIR measurements showed that gold nanoparticles made significant changes in the frequency of the CH(2) stretching bands, revealing that gold nanoparticles increased the number of gauche conformers and create a conformational change within the acyl chains of phospholipids. The transmission electron micrographs (TEM) revealed that gold nanoparticles were loaded in the liposomal bilayer. The zeta potential of DPPC liposomes had a more negative value after incorporating of Au NPs into liposomal membranes. Turbidity studies revealed that the loading of gold nanoparticles into DPPC liposomes results in shifting the temperature of the main phase transition to a lower value. The membrane fluidity of DPPC bilayer was increased by loading the gold nanoparticles as shown from rheological measurements. Knowledge gained in this study may open the door to pursuing liposomes as a viable strategy for Au NPs delivery in many diagnostic and therapeutic applications. Copyright © 2011 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Finite difference time domain calculation of transients in antennas with nonlinear loads

NASA Technical Reports Server (NTRS)

Luebbers, Raymond J.; Beggs, John H.; Kunz, Karl S.; Chamberlin, Kent

1991-01-01

Determining transient electromagnetic fields in antennas with nonlinear loads is a challenging problem. Typical methods used involve calculating frequency domain parameters at a large number of different frequencies, then applying Fourier transform methods plus nonlinear equation solution techniques. If the antenna is simple enough so that the open circuit time domain voltage can be determined independently of the effects of the nonlinear load on the antennas current, time stepping methods can be applied in a straightforward way. Here, transient fields for antennas with more general geometries are calculated directly using Finite Difference Time Domain (FDTD) methods. In each FDTD cell which contains a nonlinear load, a nonlinear equation is solved at each time step. As a test case, the transient current in a long dipole antenna with a nonlinear load excited by a pulsed plane wave is computed using this approach. The results agree well with both calculated and measured results previously published. The approach given here extends the applicability of the FDTD method to problems involving scattering from targets, including nonlinear loads and materials, and to coupling between antennas containing nonlinear loads. It may also be extended to propagation through nonlinear materials.

Assessing effect of meditation on cognitive workload using EEG signals

NASA Astrophysics Data System (ADS)

Jadhav, Narendra; Manthalkar, Ramchandra; Joshi, Yashwant

2017-06-01

Recent research suggests that meditation affects the structure and function of the brain. Cognitive load can be handled in effective way by the meditators. EEG signals are used to quantify cognitive load. The research of investigating effect of meditation on cognitive workload using EEG signals in pre and post-meditation is an open problem. The subjects for this study are young healthy 11 engineering students from our institute. The focused attention meditation practice is used for this study. EEG signals are recorded at the beginning of meditation and after four weeks of regular meditation using EMOTIV device. The subjects practiced meditation daily 20 minutes for 4 weeks. The 7 level arithmetic additions of single digit (low level) to three digits with carry (high level) are presented as cognitive load. The cognitive load indices such as arousal index, performance enhancement, neural activity, load index, engagement, and alertness are evaluated in pre and post meditation. The cognitive indices are improved in post meditation data. Power Spectral Density (PSD) feature is compared between pre and post-meditation across all subjects. The result hints that the subjects were handling cognitive load without stress (ease of cognitive functioning increased for the same load) after 4 weeks of meditation.

Effect of Repeated Screw Joint Closing and Opening Cycles and Cyclic Loading on Abutment Screw Removal Torque and Screw Thread Morphology: Scanning Electron Microscopy Evaluation.

PubMed

Arshad, Mahnaz; Mahgoli, Hosseinali; Payaminia, Leila

To evaluate the effect of repeated screw joint closing and opening cycles and cyclic loading on abutment screw removal torque and screw thread morphology using scanning electron microscopy (SEM). Three groups (n = 10 in each group) of implant-abutment-abutment screw assemblies were created. There were also 10 extra abutment screws as new screws in group 3. The abutment screws were tightened to 12 Ncm with an electronic torque meter; then they were removed and removal torque values were recorded. This sequence was repeated 5 times for group 1 and 15 times for groups 2 and 3. The same screws in groups 1 and 2 and the new screws in group 3 were then tightened to 12 Ncm; this was also followed by screw tightening to 30 Ncm and retightening to 30 Ncm 15 minutes later. Removal torque measurements were performed after screws were subjected to cyclic loading (0.5 × 10⁶ cycles; 1 Hz; 75 N). Moreover, the surface topography of one screw from each group before and after cyclic loading was evaluated with SEM and compared with an unused screw. All groups exhibited reduced removal torque values in comparison to insertion torque in each cycle. However, there was a steady trend of torque loss in each group. A comparison of the last cycle of the groups before loading showed significantly greater torque loss value in the 15th cycle of groups 2 and 3 compared with the fifth cycle of group 1 (P < .05). Nonetheless, torque loss values after loading were not shown to be significantly different from each other. Using a new screw could not significantly increase the value of removal torque. It was concluded that restricting the amount of screw tightening is more important than replacing the screw with a new one when an abutment is definitively placed.

Variability of hydrologic regimes and morphology in constructed open-ditch channels

USGS Publications Warehouse

Strock, J.S.; Magner, J.A.; Richardson, W.B.; Sadowsky, M.J.; Sands, G.R.; Venterea, R.T.; ,

2004-01-01

Open-ditch ecosystems are potential transporters of considerable loads of nutrients, sediment, pathogens and pesticides from direct inflow from agricultural land to small streams and larger rivers. Our objective was to compare hydrology and channel morphology between two experimental open-ditch channels. An open-ditch research facility incorporating a paired design was constructed during 2002 near Lamberton, MN. A200-m reach of existing drainage channel was converted into a system of four parallel channels. The facility was equipped with water level control devices and instrumentation for flow monitoring and water sample collection on upstream and downstream ends of the system. Hydrographs from simulated flow during year one indicated that paired open-ditch channels responded similarly to changes in inflow. Variability in hydrologic response between open-ditches was attributed to differences in open-ditch channel bottom elevation and vegetation density. No chemical, biological, or atmospheric measurements were made during 2003. Potential future benefits of this research include improved biological diversity and integrity of open-ditch ecosystems, reduce flood peaks and increased flow during critical low-flow periods, improved and more efficient nitrogen retention within the open-ditch ecosystem, and decreased maintenance cost associated with reduced frequency of open-ditch maintenance.

Bending and Shear Behavior of Pultruded Glass Fiber Reinforced Polymer Composite Beams With Closed and Open Sections

NASA Astrophysics Data System (ADS)

Estep, Daniel Douglas

Several advantages, such as high strength-to-weight ratio, high stiffness, superior corrosion resistance, and high fatigue and impact resistance, among others, make FRPs an attractive alternative to conventional construction materials for use in developing new structures as well as rehabilitating in-service infrastructure. As the number of infrastructure applications using FRPs grows, the need for the development of a uniform Load and Resistance Factor Design (LRFD) approach, including design procedures and examples, has become paramount. Step-by-step design procedures and easy-to-use design formulas are necessary to assure the quality and safety of FRP structural systems by reducing the possibility of design and construction errors. Since 2008, the American Society of Civil Engineers (ASCE), in coordination with the American Composites Manufacturers Association (ACMA), has overseen the development of the Pre-Standard for Load and Resistance Factor Design (LRFD) of Pultruded Fiber Reinforced Polymer (FRP) Structures using probability-based limit states design. The fifth chapter of the pre-standard focuses on the design of members in flexure and shear under different failure modes, where the current failure load prediction models proposed within have been shown to be highly inaccurate based on experimental data and evaluation performed by researchers at the West Virginia University Constructed Facilities Center. A new prediction model for determining the critical flexural load capacity of pultruded GFRP square and rectangular box beams is presented within. This model shows that the type of failure can be related to threshold values of the beam span-to-depth ratio (L/h) and total flange width-to-thickness ratio (bf /t), resulting in three governing modes of failure: local buckling failure in the compression flange (4 ≤ L/h < 6), combined strain failure at the web-flange junction (6 ≤ L/h ≤ 10), and bending failure in the tension flange (10 < L/h ≤ 42). Broadly, the proposed equations are predicting critical flexural load capacities within +/-22.3% of experimental data for all cases, with over 70% of all experimental data with within +/-10% error. A second prediction model was developed for predicting the critical lateral-torsional buckling (LTB) load for pultruded GFRP open sections, including wide flange (WF) sections and channels. Multiple LTB equations from several sources were considered and applied but yielded inaccurate results, leading to the development of this new critical buckling load prediction model based on the well-established elastic LTB strength equation for steel. By making a series of modifications to equations for calculating the weak axis moment of inertia, torsional warping constant, and torsion constant for open sections, as well as recognizing the influence of the shear lag phenomenon, the critical LTB load is predicted within +/-15.2% of experimental data for all channel and WF specimens tested and evaluated in the study.

Multi-gap high impedance plasma opening switch

DOEpatents

Mason, Rodney J.

1996-01-01

A high impedance plasma opening switch having an anode and a cathode and at least one additional electrode placed between the anode and cathode. The presence of the additional electrodes leads to the creation of additional plasma gaps which are in series, increasing the net impedance of the switch. An equivalent effect can be obtained by using two or more conventional plasma switches with their plasma gaps wired in series. Higher impedance switches can provide high current and voltage to higher impedance loads such as plasma radiation sources.

A comparison of pure mode I and mixed mode I-III cracking of an adhesive containing an open knit cloth carrier

NASA Technical Reports Server (NTRS)

Ripling, E. J.; Crosley, P. B.; Johnson, W. S.

1988-01-01

Static and fatigue tests were carried out on two commercial modified epoxy film adhesives with a wide open knit polyester carrier in order to compare crack resistance in mode I and mixed mode I-III loading. The carrier cloth is found to have a significant influence on the cracking behavior of the adhesives. The open air net carrier used in this study separates from the adhesive in mode I cracking but shreds during mixed-mode crack extension. This decreases the opening mode toughness but increases the mixed-mode toughness as compared with results obtained earlier using a heavier knit carrier. The results suggest that the type of carrier may have a far larger influence on crack resistance than is generally recognized.

Effectiveness of a stormwater collection and detention system for reducing constituent loads from bridge runoff in Pinellas County, Florida

USGS Publications Warehouse

Stoker, Y.E.

1996-01-01

The quantity and quality of stormwater runoff from the Bayside Bridge were evaluated to determine the effectiveness of the stormwater collection and detention pond system of the bridge in reducing constituent loads to Old Tampa Bay. Water-quality samples of stormwater runoff from the bridge and outflow from the detention pond were collected during and after selected storms. These samples were used to compute loads for selected constituents. Stormwater on the Bayside Bridge drained rapidly during rain events. The volume of stormwater runoff from 24 storms measured during the study ranged from 4,086 to 103,705 cubic feet. Storms were most frequent during July through September and were least frequent from February through May. Concentrations of most constituents in stormwater runoff before the bridge opened to traffic were less than or equal to concentrations measured after the bridge was opened to traffic. However, concentrations of arsenic in the outflow from the detention pond generally were greater before the bridge opened than concentrations after, and concentrations of orthophosphorus in the stormwater runoff and outflow from the pond were greater before the bridge opened than during over half the sampled storms after the bridge opened. Concentrations of most constituents measured in stormwater runoff from the bridge were greatest at the beginning of the storm and decreased as the storm continued. Variations in suspended solids, nutrients, and trace element concentrations were not always concurrent with each other. The source of the measured constituent (rainfall or road debris) and the phase of the constituent (suspended or dissolved) probably affected the timing of concentration changes. The quality of stormwater runoff from the Bayside Bridge varied with total runoff volume, with the length of the dry period before the storm, and with season. Average concentrations of suspended solids, ammonia plus organic nitrogen, nitrite plus nitrate nitrogen, orthophosphorus, phosphorus, total organic carbon, aluminum, arsenic, copper, and zinc in stormwater runoff generally were inversely related to runoff volume. The quality of outflow from the detention pond also varied during a storm event and with season. Maximum concentrations generally occurred near the beginning of a storm, and decreased as the storm continued. Maximum concentrations of many constituents occurred in June and July 1995. During the summer months, pH exceeded 9.0 while inorganic nitrogen concentrations were very low. These high pH values and low inorganic nitrogen concentrations are most likely associated with photosynthesis by algae or aquatic plants in the pond. Concentrations of nitrogen, phosphorus, and nickel in stormwater runoff were correlated with total organic carbon concentrations. Concentrations of chromium, copper, iron, nickel, lead, and zinc in stormwater runoff were correlated with aluminum concentrations. The source of these metals is probably the bridge materials and metallic debris from vehicles. The northern detention pond system of the Bayside Bridge effectively reduced concentrations of suspended solids, ammonia nitrogen, nitrite plus nitrate nitrogen, phosphorus, aluminum, cadmium, chromium, copper, iron, lead, nickel, and zinc in stormwater runoff before water discharged from the pond. However, concentrations of ammonia plus organic nitrogen, organic carbon, arsenic, and values for alkalinity, pH, and specific conductance generally were greater in outflow from the pond than in stormwater runoff from the bridge. Stormwater runoff and pond outflow for three storm events were evaluated to determine the effectiveness of the detention pond system in removing selected constituents from the stormwater runoff. Most constituents and constituent loads were reduced in the outflow from the pond. Suspended solids loads were reduced about 30 to 45 percent, inorganic nitrogen loads were reduced by about 60 to 90 percent, and loads of most trace elements

Rolling Maneuver Load Alleviation using active controls

NASA Technical Reports Server (NTRS)

Woods-Vedeler, Jessica A.; Pototzky, Anthony S.

1992-01-01

Rolling Maneuver Load Alleviation (RMLA) has been demonstrated on the Active Flexible Wing (AFW) wind tunnel model in the NASA Langley Transonic Dynamics Tunnel. The design objective was to develop a systematic approach for developing active control laws to alleviate wing incremental loads during roll maneuvers. Using linear load models for the AFW wind-tunnel model which were based on experimental measurements, two RMLA control laws were developed based on a single-degree-of-freedom roll model. The RMLA control laws utilized actuation of outboard control surface pairs to counteract incremental loads generated during rolling maneuvers and actuation of the trailing edge inboard control surface pairs to maintain roll performance. To evaluate the RMLA control laws, roll maneuvers were performed in the wind tunnel at dynamic pressures of 150, 200, and 250 psf and Mach numbers of 0.33, .38 and .44, respectively. Loads obtained during these maneuvers were compared to baseline maneuver loads. For both RMLA controllers, the incremental torsion moments were reduced by up to 60 percent at all dynamic pressures and performance times. Results for bending moment load reductions during roll maneuvers varied. In addition, in a multiple function test, RMLA and flutter suppression system control laws were operated simultaneously during roll maneuvers at dynamic pressures 11 percent above the open-loop flutter dynamic pressure.

49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

Code of Federal Regulations, 2012 CFR

2012-10-01

... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

Code of Federal Regulations, 2011 CFR

2011-10-01

... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

Code of Federal Regulations, 2013 CFR

2013-10-01

... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

49 CFR 571.219 - Standard No. 219; Windshield zone intrusion.

Code of Federal Regulations, 2014 CFR

2014-10-01

... forward control vehicles, walk-in van-type vehicles, or to open-body-type vehicles with fold-down or... tire-ground interface is in proportion to its GAWR. If the mass on any axle when the vehicle is loaded...

Performance of geogrid reinforced ballast under dynamic loading.

DOT National Transportation Integrated Search

2012-07-01

Railroad ballast consists of open graded crushed stone used as a bed for railroad track to provide stability. Over time, : ballast degrades and loses its strength. Fouling of ballast with fines has been a major issue of railway engineering. In this :...