A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage.

PubMed

Kubiak, Jeffrey M; Culyba, Matthew J; Liu, Monica Yun; Mo, Charlie Y; Goulian, Mark; Kohli, Rahul M

2017-11-17

The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway.

Mitogen-activated protein kinase signal transduction and DNA repair network are involved in aluminum-induced DNA damage and adaptive response in root cells of Allium cepa L.

PubMed Central

Panda, Brahma B.; Achary, V. Mohan M.

2014-01-01

In the current study, we studied the role of signal transduction in aluminum (Al3+)-induced DNA damage and adaptive response in root cells of Allium cepa L. The root cells in planta were treated with Al3+ (800 μM) for 3 h without or with 2 h pre-treatment of inhibitors of mitogen-activated protein kinase (MAPK), and protein phosphatase. Also, root cells in planta were conditioned with Al3+ (10 μM) for 2 h and then subjected to genotoxic challenge of ethyl methane sulfonate (EMS; 5 mM) for 3 h without or with the pre-treatment of the aforementioned inhibitors as well as the inhibitors of translation, transcription, DNA replication and repair. At the end of treatments, roots cells were assayed for cell death and/or DNA damage. The results revealed that Al3+ (800 μM)-induced significant DNA damage and cell death. On the other hand, conditioning with low dose of Al3+ induced adaptive response conferring protection of root cells from genotoxic stress caused by EMS-challenge. Pre-treatment of roots cells with the chosen inhibitors prior to Al3+-conditioning prevented or reduced the adaptive response to EMS genotoxicity. The results of this study suggested the involvement of MAPK and DNA repair network underlying Al-induced DNA damage and adaptive response to genotoxic stress in root cells of A. cepa. PMID:24926302

PAXIP1 potentiates the combination of WEE1 inhibitor AZD1775 and platinum agents in lung cancer

PubMed Central

Jhuraney, Ankita; Woods, Nicholas T.; Wright, Gabriela; Rix, Lily; Kinose, Fumi; Kroeger, Jodi L.; Remily-Wood, Elizabeth; Cress, W. Douglas; Koomen, John M.; Brantley, Stephen G.; Gray, Jhanelle E.; Haura, Eric B.; Rix, Uwe; Monteiro, Alvaro N.

2016-01-01

The DNA damage response (DDR) involves a complex network of signaling events mediated by modular protein domains such as the BRCT (BRCA1 C-terminal) domain. Thus, proteins that interact with BRCT domains and are a part of the DDR constitute potential targets for sensitization to DNA damaging chemotherapy agents. We performed a pharmacological screen to evaluate seventeen kinases, identified in a BRCT-mediated interaction network as targets to enhance platinum-based chemotherapy in lung cancer. Inhibition of mitotic kinase WEE1 was found to have the most effective response in combination with platinum compounds in lung cancer cell lines. In the BRCT-mediated interaction network, WEE1 was found in complex with PAXIP1, a protein containing six BRCT domains involved in transcription and in the cellular response to DNA damage. We show that PAXIP1 BRCT domains regulate WEE1-mediated phosphorylation of CDK1. Further, ectopic expression of PAXIP1 promotes enhanced caspase 3-mediated apoptosis in cells treated with WEE1 inhibitor AZD1775 (formerly, MK-1775) and cisplatin compared with cells treated with AZD1775 alone. Cell lines and patient-derived xenograft models expressing both PAXIP1 and WEE1 exhibited synergistic effects of AZD1775 and cisplatin. In summary, PAXIP1 is involved in sensitizing lung cancer cells to the WEE1 inhibitor AZD1775 in combination with platinum-based treatment. We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA damaging agents. PMID:27196765

Perspectives for computational modeling of cell replacement for neurological disorders

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

Aimone, James B.; Weick, Jason P.

In mathematical modeling of anatomically-constrained neural networks we provide significant insights regarding the response of networks to neurological disorders or injury. Furthermore, a logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impactmore » circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.« less

Perspectives for computational modeling of cell replacement for neurological disorders

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

Aimone, James B.; Weick, Jason P.

Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behaviormore » in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.« less

VTAC: virtual terrain assisted impact assessment for cyber attacks

NASA Astrophysics Data System (ADS)

Argauer, Brian J.; Yang, Shanchieh J.

2008-03-01

Overwhelming intrusion alerts have made timely response to network security breaches a difficult task. Correlating alerts to produce a higher level view of intrusion state of a network, thus, becomes an essential element in network defense. This work proposes to analyze correlated or grouped alerts and determine their 'impact' to services and users of the network. A network is modeled as 'virtual terrain' where cyber attacks maneuver. Overlaying correlated attack tracks on virtual terrain exhibits the vulnerabilities exploited by each track and the relationships between them and different network entities. The proposed impact assessment algorithm utilizes the graph-based virtual terrain model and combines assessments of damages caused by the attacks. The combined impact scores allow to identify severely damaged network services and affected users. Several scenarios are examined to demonstrate the uses of the proposed Virtual Terrain Assisted Impact Assessment for Cyber Attacks (VTAC).

Damage spreading in spatial and small-world random Boolean networks

NASA Astrophysics Data System (ADS)

Lu, Qiming; Teuscher, Christof

2014-02-01

The study of the response of complex dynamical social, biological, or technological networks to external perturbations has numerous applications. Random Boolean networks (RBNs) are commonly used as a simple generic model for certain dynamics of complex systems. Traditionally, RBNs are interconnected randomly and without considering any spatial extension and arrangement of the links and nodes. However, most real-world networks are spatially extended and arranged with regular, power-law, small-world, or other nonrandom connections. Here we explore the RBN network topology between extreme local connections, random small-world, and pure random networks, and study the damage spreading with small perturbations. We find that spatially local connections change the scaling of the Hamming distance at very low connectivities (K¯≪1) and that the critical connectivity of stability Ks changes compared to random networks. At higher K¯, this scaling remains unchanged. We also show that the Hamming distance of spatially local networks scales with a power law as the system size N increases, but with a different exponent for local and small-world networks. The scaling arguments for small-world networks are obtained with respect to the system sizes and strength of spatially local connections. We further investigate the wiring cost of the networks. From an engineering perspective, our new findings provide the key design trade-offs between damage spreading (robustness), the network's wiring cost, and the network's communication characteristics.

ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

PubMed

Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

2017-10-01

Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Online monitoring of seismic damage in water distribution systems

NASA Astrophysics Data System (ADS)

Liang, Jianwen; Xiao, Di; Zhao, Xinhua; Zhang, Hongwei

2004-07-01

It is shown that water distribution systems can be damaged by earthquakes, and the seismic damages cannot easily be located, especially immediately after the events. Earthquake experiences show that accurate and quick location of seismic damage is critical to emergency response of water distribution systems. This paper develops a methodology to locate seismic damage -- multiple breaks in a water distribution system by monitoring water pressure online at limited positions in the water distribution system. For the purpose of online monitoring, supervisory control and data acquisition (SCADA) technology can well be used. A neural network-based inverse analysis method is constructed for locating the seismic damage based on the variation of water pressure. The neural network is trained by using analytically simulated data from the water distribution system, and validated by using a set of data that have never been used in the training. It is found that the methodology provides an effective and practical way in which seismic damage in a water distribution system can be accurately and quickly located.

A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage

PubMed Central

2017-01-01

The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway. PMID:28826208

Damage Precursor Investigation of Fiber-Reinforced Composite Materials Under Fatigue Loads

DTIC Science & Technology

2013-09-01

19.21, 215713. Thostenson, E. T.; Chou, T.‐W. Carbon Nanotube Networks: Sensing of Distributed Strain and Damage for Life Prediction and Self Healing ...composite structural life and the goal of the proposed research program to develop self -responsive engineered composites. Over 80%‒90% of the life of a...composite material. It is also envisaged to investigate and develop self -responsive engineered composite materials that provide an accurate health

Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres

PubMed Central

Valerio-Santiago, Mauricio; de los Santos-Velázquez, Ana Isabel; Monje-Casas, Fernando

2013-01-01

When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression. PMID:24130507

Kainate and metabolic perturbation mimicking spinal injury differentially contribute to early damage of locomotor networks in the in vitro neonatal rat spinal cord.

PubMed

Taccola, G; Margaryan, G; Mladinic, M; Nistri, A

2008-08-13

Acute spinal cord injury evolves rapidly to produce secondary damage even to initially spared areas. The result is loss of locomotion, rarely reversible in man. It is, therefore, important to understand the early pathophysiological processes which affect spinal locomotor networks. Regardless of their etiology, spinal lesions are believed to include combinatorial effects of excitotoxicity and severe stroke-like metabolic perturbations. To clarify the relative contribution by excitotoxicity and toxic metabolites to dysfunction of locomotor networks, spinal reflexes and intrinsic network rhythmicity, we used, as a model, the in vitro thoraco-lumbar spinal cord of the neonatal rat treated (1 h) with either kainate or a pathological medium (containing free radicals and hypoxic/aglycemic conditions), or their combination. After washout, electrophysiological responses were monitored for 24 h and cell damage analyzed histologically. Kainate suppressed fictive locomotion irreversibly, while it reversibly blocked neuronal excitability and intrinsic bursting induced by synaptic inhibition block. This result was associated with significant neuronal loss around the central canal. Combining kainate with the pathological medium evoked extensive, irreversible damage to the spinal cord. The pathological medium alone slowed down fictive locomotion and intrinsic bursting: these oscillatory patterns remained throughout without regaining their control properties. This phenomenon was associated with polysynaptic reflex depression and preferential damage to glial cells, while neurons were comparatively spared. Our model suggests distinct roles of excitotoxicity and metabolic dysfunction in the acute damage of locomotor networks, indicating that different strategies might be necessary to treat the various early components of acute spinal cord lesion.

Comparison of Computational-Model and Experimental-Example Trained Neural Networks for Processing Speckled Fringe Patterns

NASA Technical Reports Server (NTRS)

Decker, A. J.; Fite, E. B.; Thorp, S. A.; Mehmed, O.

1998-01-01

The responses of artificial neural networks to experimental and model-generated inputs are compared for detection of damage in twisted fan blades using electronic holography. The training-set inputs, for this work, are experimentally generated characteristic patterns of the vibrating blades. The outputs are damage-flag indicators or second derivatives of the sensitivity-vector-projected displacement vectors from a finite element model. Artificial neural networks have been trained in the past with computational-model-generated training sets. This approach avoids the difficult inverse calculations traditionally used to compare interference fringes with the models. But the high modeling standards are hard to achieve, even with fan-blade finite-element models.

Comparison of Computational, Model and Experimental, Example Trained Neural Networks for Processing Speckled Fringe Patterns

NASA Technical Reports Server (NTRS)

Decker, A. J.; Fite, E. B.; Thorp, S. A.; Mehmed, O.

1998-01-01

The responses of artificial neural networks to experimental and model-generated inputs are compared for detection of damage in twisted fan blades using electronic holography. The training-set inputs, for this work, are experimentally generated characteristic patterns of the vibrating blades. The outputs are damage-flag indicators or second derivatives of the sensitivity-vector-projected displacement vectors from a finite element model. Artificial neural networks have been trained in the past with computational-model- generated training sets. This approach avoids the difficult inverse calculations traditionally used to compare interference fringes with the models. But the high modeling standards are hard to achieve, even with fan-blade finite-element models.

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response.

PubMed

Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E; Harper, J Wade; Elledge, Stephen J

2014-12-30

The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage.

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

PubMed Central

Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E.; Harper, J. Wade; Elledge, Stephen J.

2014-01-01

The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage. PMID:25512513

Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data

PubMed Central

2011-01-01

Background Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. Results We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Conclusions Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations. PMID:21693013

Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data.

PubMed

Szczurek, Ewa; Markowetz, Florian; Gat-Viks, Irit; Biecek, Przemysław; Tiuryn, Jerzy; Vingron, Martin

2011-06-21

Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.

Non-equilibrium repressor binding kinetics link DNA damage dose to transcriptional timing within the SOS gene network.

PubMed

Culyba, Matthew J; Kubiak, Jeffrey M; Mo, Charlie Y; Goulian, Mark; Kohli, Rahul M

2018-06-01

Biochemical pathways are often genetically encoded as simple transcription regulation networks, where one transcription factor regulates the expression of multiple genes in a pathway. The relative timing of each promoter's activation and shut-off within the network can impact physiology. In the DNA damage repair pathway (known as the SOS response) of Escherichia coli, approximately 40 genes are regulated by the LexA repressor. After a DNA damaging event, LexA degradation triggers SOS gene transcription, which is temporally separated into subsets of 'early', 'middle', and 'late' genes. Although this feature plays an important role in regulating the SOS response, both the range of this separation and its underlying mechanism are not experimentally defined. Here we show that, at low doses of DNA damage, the timing of promoter activities is not separated. Instead, timing differences only emerge at higher levels of DNA damage and increase as a function of DNA damage dose. To understand mechanism, we derived a series of synthetic SOS gene promoters which vary in LexA-operator binding kinetics, but are otherwise identical, and then studied their activity over a large dose-range of DNA damage. In distinction to established models based on rapid equilibrium assumptions, the data best fit a kinetic model of repressor occupancy at promoters, where the drop in cellular LexA levels associated with higher doses of DNA damage leads to non-equilibrium binding kinetics of LexA at operators. Operators with slow LexA binding kinetics achieve their minimal occupancy state at later times than operators with fast binding kinetics, resulting in a time separation of peak promoter activity between genes. These data provide insight into this remarkable feature of the SOS pathway by demonstrating how a single transcription factor can be employed to control the relative timing of each gene's transcription as a function of stimulus dose.

A network of enzymes involved in repair of oxidative DNA damage in Neisseria meningitidis

PubMed Central

Li, Yanwen; Pelicic, Vladimir; Freemont, Paul S.; Baldwin, Geoff S.; Tang, Christoph M.

2013-01-01

Although oxidative stress is a key aspect of innate immunity, little is known about how host-restricted pathogens successfully repair DNA damage. Base excision repair (BER) is responsible for correcting nucleobases damaged by oxidative stress, and is essential for bloodstream infection caused by the human pathogen, Neisseria meningitidis. We have characterised meningococcal BER enzymes involved in the recognition and removal of damaged nucleobases, and incision of the DNA backbone. We demonstrate that the bi-functional glycosylase/lyases Nth and MutM share several overlapping activities and functional redundancy. However MutM and other members of the GO system, which deal with 8-oxoG, a common lesion of oxidative damage, are not required for survival of N. meningitidis under oxidative stress. Instead, the mismatch repair pathway provides back-up for the GO system, while the lyase activity of Nth can substitute for the meningococcal AP endonuclease, NApe. Our genetic and biochemical evidence show that DNA repair is achieved through a robust network of enzymes that provides a flexible system of DNA repair. This network is likely to reflect successful adaptation to the human nasopharynx, and might provide a paradigm for DNA repair in other prokaryotes. PMID:22296581

Detection, location, and quantification of structural damage by neural-net-processed moiré profilometry

NASA Astrophysics Data System (ADS)

Grossman, Barry G.; Gonzalez, Frank S.; Blatt, Joel H.; Hooker, Jeffery A.

1992-03-01

The development of efficient high speed techniques to recognize, locate, and quantify damage is vitally important for successful automated inspection systems such as ones used for the inspection of undersea pipelines. Two critical problems must be solved to achieve these goals: the reduction of nonuseful information present in the video image and automatic recognition and quantification of extent and location of damage. Artificial neural network processed moire profilometry appears to be a promising technique to accomplish this. Real time video moire techniques have been developed which clearly distinguish damaged and undamaged areas on structures, thus reducing the amount of extraneous information input into an inspection system. Artificial neural networks have demonstrated advantages for image processing, since they can learn the desired response to a given input and are inherently fast when implemented in hardware due to their parallel computing architecture. Video moire images of pipes with dents of different depths were used to train a neural network, with the desired output being the location and severity of the damage. The system was then successfully tested with a second series of moire images. The techniques employed and the results obtained are discussed.

Filling the gap between disaster preparedness and response networks of urban emergency management: Following the 2013 Seoul Floods.

PubMed

Song, Minsun; Jung, Kyujin

2015-01-01

To examine the gap between disaster preparedness and response networks following the 2013 Seoul Floods in which the rapid transmission of disaster information and resources was impeded by severe changes of interorganizational collaboration networks. This research uses the 2013 Seoul Emergency Management Survey data that were collected before and after the floods, and total 94 organizations involving in coping with the floods were analyzed in bootstrap independent-sample t-test and social network analysis through UCINET 6 and STATA 12. The findings show that despite the primary network form that is more hierarchical, horizontal collaboration has been relatively invigorated in actual response. Also, interorganizational collaboration networks for response operations seem to be more flexible grounded on improvisation to coping with unexpected victims and damages. Local organizations under urban emergency management are recommended to tightly build a strong commitment for joint response operations through full-size exercises at the metropolitan level before a catastrophic event. Also, interorganizational emergency management networks need to be restructured by reflecting the actual response networks to reduce collaboration risk during a disaster. This research presents a critical insight into inverse thinking of the view designing urban emergency management networks and provides original evidences for filling the gap between previously coordinated networks for disaster preparedness and practical response operations after a disaster.

Interplay between Ubiquitin, SUMO, and Poly(ADP-Ribose) in the Cellular Response to Genotoxic Stress

PubMed Central

Pellegrino, Stefania; Altmeyer, Matthias

2016-01-01

Cells employ a complex network of molecular pathways to cope with endogenous and exogenous genotoxic stress. This multilayered response ensures that genomic lesions are efficiently detected and faithfully repaired in order to safeguard genome integrity. The molecular choreography at sites of DNA damage relies heavily on post-translational modifications (PTMs). Protein modifications with ubiquitin and the small ubiquitin-like modifier SUMO have recently emerged as important regulatory means to coordinate DNA damage signaling and repair. Both ubiquitylation and SUMOylation can lead to extensive chain-like protein modifications, a feature that is shared with yet another DNA damage-induced PTM, the modification of proteins with poly(ADP-ribose) (PAR). Chains of ubiquitin, SUMO, and PAR all contribute to the multi-protein assemblies found at sites of DNA damage and regulate their spatio-temporal dynamics. Here, we review recent advancements in our understanding of how ubiquitin, SUMO, and PAR coordinate the DNA damage response and highlight emerging examples of an intricate interplay between these chain-like modifications during the cellular response to genotoxic stress. PMID:27148359

HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism

PubMed Central

Conrad, E; Polonio-Vallon, T; Meister, M; Matt, S; Bitomsky, N; Herbel, C; Liebl, M; Greiner, V; Kriznik, B; Schumacher, S; Krieghoff-Henning, E; Hofmann, T G

2016-01-01

Upon severe DNA damage a cellular signalling network initiates a cell death response through activating tumour suppressor p53 in association with promyelocytic leukaemia (PML) nuclear bodies. The deacetylase Sirtuin 1 (SIRT1) suppresses cell death after DNA damage by antagonizing p53 acetylation. To facilitate efficient p53 acetylation, SIRT1 function needs to be restricted. How SIRT1 activity is regulated under these conditions remains largely unclear. Here we provide evidence that SIRT1 activity is limited upon severe DNA damage through phosphorylation by the DNA damage-responsive kinase HIPK2. We found that DNA damage provokes interaction of SIRT1 and HIPK2, which phosphorylates SIRT1 at Serine 682 upon lethal damage. Furthermore, upon DNA damage SIRT1 and HIPK2 colocalize at PML nuclear bodies, and PML depletion abrogates DNA damage-induced SIRT1 Ser682 phosphorylation. We show that Ser682 phosphorylation inhibits SIRT1 activity and impacts on p53 acetylation, apoptotic p53 target gene expression and cell death. Mechanistically, we found that DNA damage-induced SIRT1 Ser682 phosphorylation provokes disruption of the complex between SIRT1 and its activator AROS. Our findings indicate that phosphorylation-dependent restriction of SIRT1 activity by HIPK2 shapes the p53 response. PMID:26113041

Interface Control Document for the EMPACT Module that Estimates Electric Power Transmission System Response to EMP-Caused Damage

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

Werley, Kenneth Alan; Mccown, Andrew William

The EPREP code is designed to evaluate the effects of an Electro-Magnetic Pulse (EMP) on the electric power transmission system. The EPREP code embodies an umbrella framework that allows a user to set up analysis conditions and to examine analysis results. The code links to three major physics/engineering modules. The first module describes the EM wave in space and time. The second module evaluates the damage caused by the wave on specific electric power (EP) transmission system components. The third module evaluates the consequence of the damaged network on its (reduced) ability to provide electric power to meet demand. Thismore » third module is the focus of the present paper. The EMPACT code serves as the third module. The EMPACT name denotes EMP effects on Alternating Current Transmission systems. The EMPACT algorithms compute electric power transmission network flow solutions under severely damaged network conditions. Initial solutions are often characterized by unacceptible network conditions including line overloads and bad voltages. The EMPACT code contains algorithms to adjust optimally network parameters to eliminate network problems while minimizing outages. System adjustments include automatically adjusting control equipment (generator V control, variable transformers, and variable shunts), as well as non-automatic control of generator power settings and minimal load shedding. The goal is to evaluate the minimal loss of customer load under equilibrium (steady-state) conditions during peak demand.« less

Design of robust flow processing networks with time-programmed responses

NASA Astrophysics Data System (ADS)

Kaluza, P.; Mikhailov, A. S.

2012-04-01

Can artificially designed networks reach the levels of robustness against local damage which are comparable with those of the biochemical networks of a living cell? We consider a simple model where the flow applied to an input node propagates through the network and arrives at different times to the output nodes, thus generating a pattern of coordinated responses. By using evolutionary optimization algorithms, functional networks - with required time-programmed responses - were constructed. Then, continuing the evolution, such networks were additionally optimized for robustness against deletion of individual nodes or links. In this manner, large ensembles of functional networks with different kinds of robustness were obtained, making statistical investigations and comparison of their structural properties possible. We have found that, generally, different architectures are needed for various kinds of robustness. The differences are statistically revealed, for example, in the Laplacian spectra of the respective graphs. On the other hand, motif distributions of robust networks do not differ from those of the merely functional networks; they are found to belong to the first Alon superfamily, the same as that of the gene transcription networks of single-cell organisms.

Non linear processes modulated by low doses of radiation exposure

NASA Astrophysics Data System (ADS)

Mariotti, Luca; Ottolenghi, Andrea; Alloni, Daniele; Babini, Gabriele; Morini, Jacopo; Baiocco, Giorgio

The perturbation induced by radiation impinging on biological targets can stimulate the activation of several different pathways, spanning from the DNA damage processing to intra/extra -cellular signalling. In the mechanistic investigation of radiobiological damage this complex “system” response (e.g. omics, signalling networks, micro-environmental modifications, etc.) has to be taken into account, shifting from a focus on the DNA molecule solely to a systemic/collective view. An additional complication comes from the finding that the individual response of each of the involved processes is often not linear as a function of the dose. In this context, a systems biology approach to investigate the effects of low dose irradiations on intra/extra-cellular signalling will be presented, where low doses of radiation act as a mild perturbation of a robustly interconnected network. Results obtained through a multi-level investigation of both DNA damage repair processes (e.g. gamma-H2AX response) and of the activation kinetics for intra/extra cellular signalling pathways (e.g. NFkB activation) show that the overall cell response is dominated by non-linear processes - such as negative feedbacks - leading to possible non equilibrium steady states and to a poor signal-to-noise ratio. Together with experimental data of radiation perturbed pathways, different modelling approaches will be also discussed.

Self-diagnostic thermal protection systems for future spacecraft

NASA Astrophysics Data System (ADS)

Hanlon, Alaina B.

The thermal protection system (TPS) represents the greatest risk factor after propulsion for any transatmospheric mission (Dr. Charles Smith, NASA ARC). Any damage to the TPS leaves the space vehicle vulnerable and could result in the loss of human life as happened in the Columbia accident. Aboard the current Space Shuttle Orbiters no system exists to notify the astronauts or ground control if the thermal protection system has been damaged. Through this research, a proof-of-concept monitoring system was developed. The system has two specific applications for thermal protection systems: (1) Improving models used to predict thermal and mechanical response of TPS materials, and (2) Self-diagnosing damage within regions of the TPS and communicating the damage to the appropriate personnel over a potentially unstable network. Mechanical damage is among the most important things to protect the TPS against. Methods to detect the primary types of mechanical damage suffered by thermal protection systems have been developed. Lightweight, low-power sensors were developed to detect any cracks in small regions of a TPS. Implementation of a network of these sensors within 10's to 1000's of regions will eventually provide high spatial resolution of damage detection; allowing for detection of holes in the TPS. Also important in thermal protection material development is to know the ablation rates and time/temperature response of the materials. A new type of sensor has been developed to monitor temperature at different depths within thermal protection materials. The signals being transmitted through the sensors can be multiplexed to allow for mechanical damage and temperature to be monitored using the same sensor.

The Replication Stress Response in Pancreatic Cancer

DTIC Science & Technology

2013-10-01

network that recognizes challenges to DNA replication and mobilizes diverse activities to maintain genome integrity. The RSR is critical for the...pancreatic cancer cells. We further validated positive hits be deconvolution of individual siRNAs and began work on determining their activities in DNA replication and DNA damage responses.

Dynamic control of type I IFN signalling by an integrated network of negative regulators.

PubMed

Porritt, Rebecca A; Hertzog, Paul J

2015-03-01

Whereas type I interferons (IFNs) have critical roles in protection from pathogens, excessive IFN responses contribute to pathology in both acute and chronic settings, pointing to the importance of balancing activating signals with regulatory mechanisms that appropriately tune the response. Here we review evidence for an integrated network of negative regulators of IFN production and action, which function at all levels of the activating and effector signalling pathways. We propose that the aim of this extensive network is to limit tissue damage while enabling an IFN response that is temporally appropriate and of sufficient magnitude. Understanding the architecture and dynamics of this network, and how it differs in distinct tissues, will provide new insights into IFN biology and aid the design of more effective therapeutics. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Eigenvector centrality is a metric of elastomer modulus, heterogeneity, and damage

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

Welch, Jr., Paul Michael; Welch, Cynthia F.

Here, we present an application of eigenvector centrality to encode the connectivity of polymer networks resolved at the micro- and meso-scopic length scales. This method captures the relative importance of different nodes within the network structure and provides a route toward the development of a statistical mechanics model that correlates connectivity with mechanical response. This scheme may be informed by analytical and semi-analytical models for the network structure, or through direct experimental examination. It may be used to predict the reduction in mechanical performance for heterogeneous materials subjected to specific modes of damage. Here, we develop the method and demonstratemore » that it leads to the prediction of established trends in elastomers. We also apply the model to the case of a self-healing polymer network reported in the literature, extracting insight about the fraction of bonds broken and re-formed during strain and recovery.« less

Eigenvector centrality is a metric of elastomer modulus, heterogeneity, and damage

DOE PAGES

Welch, Jr., Paul Michael; Welch, Cynthia F.

2017-04-27

Here, we present an application of eigenvector centrality to encode the connectivity of polymer networks resolved at the micro- and meso-scopic length scales. This method captures the relative importance of different nodes within the network structure and provides a route toward the development of a statistical mechanics model that correlates connectivity with mechanical response. This scheme may be informed by analytical and semi-analytical models for the network structure, or through direct experimental examination. It may be used to predict the reduction in mechanical performance for heterogeneous materials subjected to specific modes of damage. Here, we develop the method and demonstratemore » that it leads to the prediction of established trends in elastomers. We also apply the model to the case of a self-healing polymer network reported in the literature, extracting insight about the fraction of bonds broken and re-formed during strain and recovery.« less

TP53 regulates miRNA association with AGO2 to remodel the miRNA-mRNA interaction network.

PubMed

Krell, Jonathan; Stebbing, Justin; Carissimi, Claudia; Dabrowska, Aleksandra F; de Giorgio, Alexander; Frampton, Adam E; Harding, Victoria; Fulci, Valerio; Macino, Giuseppe; Colombo, Teresa; Castellano, Leandro

2016-03-01

DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage-induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA-mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2-miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis. © 2016 Krell et al.; Published by Cold Spring Harbor Laboratory Press.

The SOS response is permitted in Escherichia coli strains deficient in the expression of the mazEF pathway.

PubMed

Kalderon, Ziva; Kumar, Sathish; Engelberg-Kulka, Hanna

2014-01-01

The Escherichia coli (E. coli) SOS response is the largest, most complex, and best characterized bacterial network induced by DNA damage. It is controlled by a complex network involving the RecA and LexA proteins. We have previously shown that the SOS response to DNA damage is inhibited by various elements involved in the expression of the E. coli toxin-antitoxin mazEF pathway. Since the mazEF module is present on the chromosomes of most E. coli strains, here we asked: Why is the SOS response found in so many E. coli strains? Is the mazEF module present but inactive in those strains? We examined three E. coli strains used for studies of the SOS response, strains AB1932, BW25113, and MG1655. We found that each of these strains is either missing or inhibiting one of several elements involved in the expression of the mazEF-mediated death pathway. Thus, the SOS response only takes place in E. coli cells in which one or more elements of the E. coli toxin-antitoxin module mazEF or its downstream pathway is not functioning.

The SOS Response is Permitted in Escherichia coli Strains Deficient in the Expression of the mazEF Pathway

PubMed Central

Kalderon, Ziva; Kumar, Sathish; Engelberg-Kulka, Hanna

2014-01-01

The Escherichia coli (E. coli) SOS response is the largest, most complex, and best characterized bacterial network induced by DNA damage. It is controlled by a complex network involving the RecA and LexA proteins. We have previously shown that the SOS response to DNA damage is inhibited by various elements involved in the expression of the E. coli toxin-antitoxin mazEF pathway. Since the mazEF module is present on the chromosomes of most E. coli strains, here we asked: Why is the SOS response found in so many E. coli strains? Is the mazEF module present but inactive in those strains? We examined three E. coli strains used for studies of the SOS response, strains AB1932, BW25113, and MG1655. We found that each of these strains is either missing or inhibiting one of several elements involved in the expression of the mazEF-mediated death pathway. Thus, the SOS response only takes place in E. coli cells in which one or more elements of the E. coli toxin-antitoxin module mazEF or its downstream pathway is not functioning. PMID:25470502

Genome-wide characterization of differentially expressed genes provides insights into regulatory network of heat stress response in radish (Raphanus sativus L.).

PubMed

Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-03-01

Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.

Analyses of the response of a complex weighted network to nodes removal strategies considering links weight: The case of the Beijing urban road system

NASA Astrophysics Data System (ADS)

Bellingeri, Michele; Lu, Zhe-Ming; Cassi, Davide; Scotognella, Francesco

2018-02-01

Complex network response to node loss is a central question in different fields of science ranging from physics, sociology, biology to ecology. Previous studies considered binary networks where the weight of the links is not accounted for. However, in real-world networks the weights of connections can be widely different. Here, we analyzed the response of real-world road traffic complex network of Beijing, the most prosperous city in China. We produced nodes removal attack simulations using classic binary node features and we introduced weighted ranks for node importance. We measured the network functioning during nodes removal with three different parameters: the size of the largest connected cluster (LCC), the binary network efficiency (Bin EFF) and the weighted network efficiency (Weg EFF). We find that removing nodes according to weighted rank, i.e. considering the weight of the links as a number of taxi flows along the roads, produced in general the highest damage in the system. Our results show that: (i) in order to model Beijing road complex networks response to nodes (intersections) failure, it is necessary to consider the weight of the links; (ii) to discover the best attack strategy, it is important to use nodes rank accounting links weight.

Dynamic fiber Bragg gratings based health monitoring system of composite aerospace structures

NASA Astrophysics Data System (ADS)

Panopoulou, A.; Loutas, T.; Roulias, D.; Fransen, S.; Kostopoulos, V.

2011-09-01

The main purpose of the current work is to develop a new system for structural health monitoring of composite aerospace structures based on real-time dynamic measurements, in order to identify the structural state condition. Long-gauge Fibre Bragg Grating (FBG) optical sensors were used for monitoring the dynamic response of the composite structure. The algorithm that was developed for structural damage detection utilizes the collected dynamic response data, analyzes them in various ways and through an artificial neural network identifies the damage state and its location. Damage was simulated by slightly varying locally the mass of the structure (by adding a known mass) at different zones of the structure. Lumped masses in different locations upon the structure alter the eigen-frequencies in a way similar to actual damage. The structural dynamic behaviour has been numerically simulated and experimentally verified by means of modal testing on two different composite aerospace structures. Advanced digital signal processing techniques, e.g. the wavelet transform (WT), were used for the analysis of the dynamic response for feature extraction. WT's capability of separating the different frequency components in the time domain without loosing frequency information makes it a versatile tool for demanding signal processing applications. The use of WT is also suggested by the no-stationary nature of dynamic response signals and the opportunity of evaluating the temporal evolution of their frequency contents. Feature extraction is the first step of the procedure. The extracted features are effective indices of damage size and location. The classification step comprises of a feed-forward back propagation network, whose output determines the simulated damage location. Finally, dedicated training and validation activities were carried out by means of numerical simulations and experimental procedures. Experimental validation was performed initially on a flat stiffened panel, representing a section of a typical aeronautical structure, manufactured and tested in the lab and, as a second step, on a scaled up space oriented structure, which is a composite honeycomb plate, used as a deployment base for antenna arrays. An integrated FBG sensor network, based on the advantage of multiplexing, was mounted on both structures and different excitation positions and boundary conditions were used. The analysis of operational dynamic responses was employed to identify both the damage and its position. The system that was designed and tested initially on the thin composite panel, was successfully validated on the larger honeycomb structure. Numerical simulation of both structures was used as a support tool at all the steps of the work providing among others the location of the optical sensors used. The proposed work will be the base for the whole system qualification and validation on an antenna reflector in future work.

A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses

PubMed Central

Liang, Qin; Dexheimer, Thomas S; Zhang, Ping; Rosenthal, Andrew S; Villamil, Mark A; You, Changjun; Zhang, Qiuting; Chen, Junjun; Ott, Christine A; Sun, Hongmao; Luci, Diane K; Yuan, Bifeng; Simeonov, Anton; Jadhav, Ajit; Xiao, Hui; Wang, Yinsheng; Maloney, David J; Zhuang, Zhihao

2014-01-01

Protein ubiquitination and deubiquitination are central to the control of a large number of cellular pathways and signaling networks in eukaryotes. Although the essential roles of ubiquitination have been established in the eukaryotic DNA damage response, the deubiquitination process remains poorly defined. Chemical probes that perturb the activity of deubiquitinases (DUBs) are needed to characterize the cellular function of deubiquitination. Here we report ML323 (2), a highly potent inhibitor of the USP1-UAF1 deubiquitinase complex with excellent selectivity against human DUBs, deSUMOylase, deneddylase and unrelated proteases. Using ML323, we interrogated deubiquitination in the cellular response to UV- and cisplatin-induced DNA damage and revealed new insights into the requirement of deubiquitination in the DNA translesion synthesis and Fanconi anemia pathways. Moreover, ML323 potentiates cisplatin cytotoxicity in non-small cell lung cancer and osteosarcoma cells. Our findings point to USP1-UAF1 as a key regulator of the DNA damage response and a target for overcoming resistance to the platinum-based anticancer drugs. PMID:24531842

A software framework for assessing the resilience of drinking ...

EPA Pesticide Factsheets

Journal article This paper introduces a new software tool called the Water Network Tool for Resilience (WNTR) that water utilities can use to assess their resilience to disasters. A case study of an earthquake is included that results in damage to pipes and tanks, fires, and power outages. The utility uses several response strategies including fixing damaged pipes and tanks, restoring power, fighting fires, and implementing conservation.

Citizen sensors for SHM: use of accelerometer data from smartphones.

PubMed

Feng, Maria; Fukuda, Yoshio; Mizuta, Masato; Ozer, Ekin

2015-01-29

Ubiquitous smartphones have created a significant opportunity to form a low-cost wireless Citizen Sensor network and produce big data for monitoring structural integrity and safety under operational and extreme loads. Such data are particularly useful for rapid assessment of structural damage in a large urban setting after a major event such as an earthquake. This study explores the utilization of smartphone accelerometers for measuring structural vibration, from which structural health and post-event damage can be diagnosed. Widely available smartphones are tested under sinusoidal wave excitations with frequencies in the range relevant to civil engineering structures. Large-scale seismic shaking table tests, observing input ground motion and response of a structural model, are carried out to evaluate the accuracy of smartphone accelerometers under operational, white-noise and earthquake excitations of different intensity. Finally, the smartphone accelerometers are tested on a dynamically loaded bridge. The extensive experiments show satisfactory agreements between the reference and smartphone sensor measurements in both time and frequency domains, demonstrating the capability of the smartphone sensors to measure structural responses ranging from low-amplitude ambient vibration to high-amplitude seismic response. Encouraged by the results of this study, the authors are developing a citizen-engaging and data-analytics crowdsourcing platform towards a smartphone-based Citizen Sensor network for structural health monitoring and post-event damage assessment applications.

Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.

PubMed

Gao, Bo; Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-Hua; Xue, Dongbo

2017-01-01

Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including "immune response" as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.

Structural Health Monitoring and Impact Detection Using Neural Networks for Damage Characterization

NASA Technical Reports Server (NTRS)

Ross, Richard W.

2006-01-01

Detection of damage due to foreign object impact is an important factor in the development of new aerospace vehicles. Acoustic waves generated on impact can be detected using a set of piezoelectric transducers, and the location of impact can be determined by triangulation based on the differences in the arrival time of the waves at each of the sensors. These sensors generate electrical signals in response to mechanical motion resulting from the impact as well as from natural vibrations. Due to electrical noise and mechanical vibration, accurately determining these time differentials can be challenging, and even small measurement inaccuracies can lead to significant errors in the computed damage location. Wavelet transforms are used to analyze the signals at multiple levels of detail, allowing the signals resulting from the impact to be isolated from ambient electromechanical noise. Data extracted from these transformed signals are input to an artificial neural network to aid in identifying the moment of impact from the transformed signals. By distinguishing which of the signal components are resultant from the impact and which are characteristic of noise and normal aerodynamic loads, the time differentials as well as the location of damage can be accurately assessed. The combination of wavelet transformations and neural network processing results in an efficient and accurate approach for passive in-flight detection of foreign object damage.

Dynamical analysis of cellular ageing by modeling of gene regulatory network based attractor landscape.

PubMed

Chong, Ket Hing; Zhang, Xiaomeng; Zheng, Jie

2018-01-01

Ageing is a natural phenomenon that is inherently complex and remains a mystery. Conceptual model of cellular ageing landscape was proposed for computational studies of ageing. However, there is a lack of quantitative model of cellular ageing landscape. This study aims to investigate the mechanism of cellular ageing in a theoretical model using the framework of Waddington's epigenetic landscape. We construct an ageing gene regulatory network (GRN) consisting of the core cell cycle regulatory genes (including p53). A model parameter (activation rate) is used as a measure of the accumulation of DNA damage. Using the bifurcation diagrams to estimate the parameter values that lead to multi-stability, we obtained a conceptual model for capturing three distinct stable steady states (or attractors) corresponding to homeostasis, cell cycle arrest, and senescence or apoptosis. In addition, we applied a Monte Carlo computational method to quantify the potential landscape, which displays: I) one homeostasis attractor for low accumulation of DNA damage; II) two attractors for cell cycle arrest and senescence (or apoptosis) in response to high accumulation of DNA damage. Using the Waddington's epigenetic landscape framework, the process of ageing can be characterized by state transitions from landscape I to II. By in silico perturbations, we identified the potential landscape of a perturbed network (inactivation of p53), and thereby demonstrated the emergence of a cancer attractor. The simulated dynamics of the perturbed network displays a landscape with four basins of attraction: homeostasis, cell cycle arrest, senescence (or apoptosis) and cancer. Our analysis also showed that for the same perturbed network with low DNA damage, the landscape displays only the homeostasis attractor. The mechanistic model offers theoretical insights that can facilitate discovery of potential strategies for network medicine of ageing-related diseases such as cancer.

Satellite Image Classification of Building Damages Using Airborne and Satellite Image Samples in a Deep Learning Approach

NASA Astrophysics Data System (ADS)

Duarte, D.; Nex, F.; Kerle, N.; Vosselman, G.

2018-05-01

The localization and detailed assessment of damaged buildings after a disastrous event is of utmost importance to guide response operations, recovery tasks or for insurance purposes. Several remote sensing platforms and sensors are currently used for the manual detection of building damages. However, there is an overall interest in the use of automated methods to perform this task, regardless of the used platform. Owing to its synoptic coverage and predictable availability, satellite imagery is currently used as input for the identification of building damages by the International Charter, as well as the Copernicus Emergency Management Service for the production of damage grading and reference maps. Recently proposed methods to perform image classification of building damages rely on convolutional neural networks (CNN). These are usually trained with only satellite image samples in a binary classification problem, however the number of samples derived from these images is often limited, affecting the quality of the classification results. The use of up/down-sampling image samples during the training of a CNN, has demonstrated to improve several image recognition tasks in remote sensing. However, it is currently unclear if this multi resolution information can also be captured from images with different spatial resolutions like satellite and airborne imagery (from both manned and unmanned platforms). In this paper, a CNN framework using residual connections and dilated convolutions is used considering both manned and unmanned aerial image samples to perform the satellite image classification of building damages. Three network configurations, trained with multi-resolution image samples are compared against two benchmark networks where only satellite image samples are used. Combining feature maps generated from airborne and satellite image samples, and refining these using only the satellite image samples, improved nearly 4 % the overall satellite image classification of building damages.

Structural health monitoring for bolt loosening via a non-invasive vibro-haptics human-machine cooperative interface

NASA Astrophysics Data System (ADS)

Pekedis, Mahmut; Mascerañas, David; Turan, Gursoy; Ercan, Emre; Farrar, Charles R.; Yildiz, Hasan

2015-08-01

For the last two decades, developments in damage detection algorithms have greatly increased the potential for autonomous decisions about structural health. However, we are still struggling to build autonomous tools that can match the ability of a human to detect and localize the quantity of damage in structures. Therefore, there is a growing interest in merging the computational and cognitive concepts to improve the solution of structural health monitoring (SHM). The main object of this research is to apply the human-machine cooperative approach on a tower structure to detect damage. The cooperation approach includes haptic tools to create an appropriate collaboration between SHM sensor networks, statistical compression techniques and humans. Damage simulation in the structure is conducted by releasing some of the bolt loads. Accelerometers are bonded to various locations of the tower members to acquire the dynamic response of the structure. The obtained accelerometer results are encoded in three different ways to represent them as a haptic stimulus for the human subjects. Then, the participants are subjected to each of these stimuli to detect the bolt loosened damage in the tower. Results obtained from the human-machine cooperation demonstrate that the human subjects were able to recognize the damage with an accuracy of 88 ± 20.21% and response time of 5.87 ± 2.33 s. As a result, it is concluded that the currently developed human-machine cooperation SHM may provide a useful framework to interact with abstract entities such as data from a sensor network.

Predicting effects of structural stress in a genome-reduced model bacterial metabolism

NASA Astrophysics Data System (ADS)

Güell, Oriol; Sagués, Francesc; Serrano, M. Ángeles

2012-08-01

Mycoplasma pneumoniae is a human pathogen recently proposed as a genome-reduced model for bacterial systems biology. Here, we study the response of its metabolic network to different forms of structural stress, including removal of individual and pairs of reactions and knockout of genes and clusters of co-expressed genes. Our results reveal a network architecture as robust as that of other model bacteria regarding multiple failures, although less robust against individual reaction inactivation. Interestingly, metabolite motifs associated to reactions can predict the propagation of inactivation cascades and damage amplification effects arising in double knockouts. We also detect a significant correlation between gene essentiality and damages produced by single gene knockouts, and find that genes controlling high-damage reactions tend to be expressed independently of each other, a functional switch mechanism that, simultaneously, acts as a genetic firewall to protect metabolism. Prediction of failure propagation is crucial for metabolic engineering or disease treatment.

Assessment of air pollution impacts on vegetation in South Africa

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

Botha, A.T.

1989-01-01

Field surveys and biomonitoring network experiments were conducted in selected areas in South Africa to assess possible air pollution damage to vegetation. During field surveys, atmospheric fluoride was identified as an important pollutant that damaged vegetation in residential areas north of Cape Town. Gaseous air pollutants, including acid deposition and acidic mist, probably play a major role in the development of characteristic air pollution injury symptoms observed on pine trees in the Eastern Transvaal area. The impact of urban air pollution in the Cape Town area was evaluated by exposing bio-indicator plants in a network of eight biomonitoring network stationsmore » from June 1985 to May 1988. Sensitive Freesia and Gladiolus cultivars were used to biomonitor atmospheric fluoride, while a green bean cultivar was used as a biomonitor of atmospheric sulfur dioxide and ozone. At one location, bio-indicator plants were simultaneously exposed in a biomonitoring network station, open-top chambers, as well as in open plots. The responses of plants grown under these different conditions were compared.« less

The Accelerometric Networks in Istanbul

NASA Astrophysics Data System (ADS)

Zulfikar, Can; Alcik, Hakan; Mert, Aydin; Tahtasizoglu, Bahar; Kafadar, Nafiz; Korkmaz, Ahmet; Ozel, Oguz; Erdik, Mustafa

2010-05-01

In recent years several strong motion networks have been established in Istanbul with a preparation purpose for future probable earthquake. This study addresses the introduction of current seismic networks and presentation of some recent results recorded in these networks. Istanbul Earthquake Early Warning System Istanbul Earthquake Early Warning System has ten strong motion stations which were installed as close as possible to Marmara Sea main fault zone. Continuous on-line data from these stations via digital radio modem provide early warning for potentially disastrous earthquakes. Considering the complexity of fault rupture and the short fault distances involved, a simple and robust Early Warning algorithm, based on the exceedance of specified threshold time domain amplitude levels is implemented. The current algorithm compares the band-pass filtered accelerations and the cumulative absolute velocity (CAV) with specified threshold levels. The bracketed CAV window values that will be put into practice are accepted as to be 0.20, 0.40 and 0.70 m/s for three alarm levels, respectively. Istanbul Earthquake Rapid Response System Istanbul Earthquake Rapid Response System has one hundred 18 bit-resolution strong motion accelerometers which were placed in quasi-free field locations (basement of small buildings) in the populated areas of the city, within an area of approximately 50x30km, to constitute a network that will enable early damage assessment and rapid response information after a damaging earthquake. Early response information is achieved through fast acquisition and analysis of processed data obtained from the network. The stations are routinely interrogated on regular basis by the main data center. After triggered by an earthquake, each station processes the streaming strong motion data to yield the spectral accelerations at specific periods and sends these parameters in the form of SMS messages at every 20s directly to the main data center through a designated GSM network and through a microwave system. A shake map and damage distribution map (using aggregate building inventories and fragility curves) will then be automatically generated using the algorithm developed for this purpose. Loss assessment studies are complemented by a large citywide digital database on the topography, geology, soil conditions, building, infrastructure and lifeline inventory. The shake and damage maps will be conveyed to the governor's and mayor's offices and army headquarters within 3 minutes using radio modem and GPRS communication. Self Organizing Seismic Early Warning Information Network (SOSEWIN) in Atakoy District SOSEWIN sensors were developed by GFZ and Humbold University as part of SAFER project and EDIM project, and with cooperation of KOERI, the sensors were installed in Atakoy district of Istanbul city with Early Warning purpose. The main features of the SOSEWIN system are each sensing unit is comprised of low-cost components, undertakes its own seismological data processing, analysis and archiving, and its self-organizing capability with wireless mesh network communication. Seismic Network in Important Structures Some of the critical structures located in Istanbul city such as Fatih Sultan Mehmet Suspension Bridge which is connecting Asian and European sides of the city, Hagia Sophia Museum and Suleymaniye Mosque which are historical structures with an age of over 1000 years and 450 years respectively, . Kanyon Tower&Mall, Trakya Elektrik (formerly ENRON) and Isbank Tower (ISKULE) are monitorized to observe their seismic behaviors.

Programmable cells: Interfacing natural and engineered gene networks

NASA Astrophysics Data System (ADS)

Kobayashi, Hideki; Kærn, Mads; Araki, Michihiro; Chung, Kristy; Gardner, Timothy S.; Cantor, Charles R.; Collins, James J.

2004-06-01

Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: (i) the SOS signaling pathway responding to DNA damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of "plug-and-play" genetic circuitry that can be used to create cells with programmable behaviors. heterologous gene expression | synthetic biology | Escherichia coli

Distinct mechanisms act in concert to mediate cell cycle arrest.

PubMed

Toettcher, Jared E; Loewer, Alexander; Ostheimer, Gerard J; Yaffe, Michael B; Tidor, Bruce; Lahav, Galit

2009-01-20

In response to DNA damage, cells arrest at specific stages in the cell cycle. This arrest must fulfill at least 3 requirements: it must be activated promptly; it must be sustained as long as damage is present to prevent loss of genomic information; and after the arrest, cells must re-enter into the appropriate cell cycle phase to ensure proper ploidy. Multiple molecular mechanisms capable of arresting the cell cycle have been identified in mammalian cells; however, it is unknown whether each mechanism meets all 3 requirements or whether they act together to confer specific functions to the arrest. To address this question, we integrated mathematical models describing the cell cycle and the DNA damage signaling networks and tested the contributions of each mechanism to cell cycle arrest and re-entry. Predictions from this model were then tested with quantitative experiments to identify the combined action of arrest mechanisms in irradiated cells. We find that different arrest mechanisms serve indispensable roles in the proper cellular response to DNA damage over time: p53-independent cyclin inactivation confers immediate arrest, whereas p53-dependent cyclin downregulation allows this arrest to be sustained. Additionally, p21-mediated inhibition of cyclin-dependent kinase activity is indispensable for preventing improper cell cycle re-entry and endoreduplication. This work shows that in a complex signaling network, seemingly redundant mechanisms, acting in a concerted fashion, can achieve a specific cellular outcome.

A Data-Driven Response Virtual Sensor Technique with Partial Vibration Measurements Using Convolutional Neural Network.

PubMed

Sun, Shan-Bin; He, Yuan-Yuan; Zhou, Si-Da; Yue, Zhen-Jiang

2017-12-12

Measurement of dynamic responses plays an important role in structural health monitoring, damage detection and other fields of research. However, in aerospace engineering, the physical sensors are limited in the operational conditions of spacecraft, due to the severe environment in outer space. This paper proposes a virtual sensor model with partial vibration measurements using a convolutional neural network. The transmissibility function is employed as prior knowledge. A four-layer neural network with two convolutional layers, one fully connected layer, and an output layer is proposed as the predicting model. Numerical examples of two different structural dynamic systems demonstrate the performance of the proposed approach. The excellence of the novel technique is further indicated using a simply supported beam experiment comparing to a modal-model-based virtual sensor, which uses modal parameters, such as mode shapes, for estimating the responses of the faulty sensors. The results show that the presented data-driven response virtual sensor technique can predict structural response with high accuracy.

A Data-Driven Response Virtual Sensor Technique with Partial Vibration Measurements Using Convolutional Neural Network

PubMed Central

Sun, Shan-Bin; He, Yuan-Yuan; Zhou, Si-Da; Yue, Zhen-Jiang

2017-01-01

Measurement of dynamic responses plays an important role in structural health monitoring, damage detection and other fields of research. However, in aerospace engineering, the physical sensors are limited in the operational conditions of spacecraft, due to the severe environment in outer space. This paper proposes a virtual sensor model with partial vibration measurements using a convolutional neural network. The transmissibility function is employed as prior knowledge. A four-layer neural network with two convolutional layers, one fully connected layer, and an output layer is proposed as the predicting model. Numerical examples of two different structural dynamic systems demonstrate the performance of the proposed approach. The excellence of the novel technique is further indicated using a simply supported beam experiment comparing to a modal-model-based virtual sensor, which uses modal parameters, such as mode shapes, for estimating the responses of the faulty sensors. The results show that the presented data-driven response virtual sensor technique can predict structural response with high accuracy. PMID:29231868

A Global Protein Kinase and Phosphatase Interaction Network in Yeast

PubMed Central

Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

2011-01-01

The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

Involvement of Matrin 3 and SFPQ/NONO in the DNA damage response.

PubMed

Salton, Maayan; Lerenthal, Yaniv; Wang, Shih-Ya; Chen, David J; Shiloh, Yosef

2010-04-15

The DNA damage response (DDR) is a complex signaling network that is induced by DNA lesions and vigorously activated by double strand breaks (DSBs). The DSB response is mobilized by the nuclear protein kinase ATM, which phosphorylates key players in its various branches. SFPQ (PSF) and NONO (p54) are nuclear proteins that interact with each other and have diverse roles in nucleic acids metabolism. The SFPQ/NONO heterodimer was previously found to enhance DNA strand break rejoining in vitro. Our attention was drawn to these two proteins as they interact with the nuclear matrix protein Matrin 3 (MATR3), which we found to be a novel ATM target. We asked whether SFPQ and NONO too are involved in the DSB response. Proteins that function at the early phase of this response are often recruited to the damaged sites. We observed rapid recruitment of SFPQ/NONO to sites of DNA damage induced by laser microbeam. In MATR3 knockdown cells SFPQ/NONO retention at DNA damage sites was prolonged. SFPQ and MATR3 depletion led to abnormal accumulation of cells at the S-phase of the cell cycle following treatment with the radiomimetic chemical neocarzinostatin. Notably, proteins involved in DSB repair via nonhomologous end-joining co-immunoprecipitated with NONO; SFPQ depletion delayed DSB repair. Collectively the data suggest that SFPQ, NONO and MATR3 are involved in the early stage of the DSB response, setting the scene for DSB repair.

Immobilized Metal Affinity Chromatography Coupled to Multiple Reaction Monitoring Enables Reproducible Quantification of Phospho-signaling*

PubMed Central

Kennedy, Jacob J.; Yan, Ping; Zhao, Lei; Ivey, Richard G.; Voytovich, Uliana J.; Moore, Heather D.; Lin, Chenwei; Pogosova-Agadjanyan, Era L.; Stirewalt, Derek L.; Reding, Kerryn W.; Whiteaker, Jeffrey R.; Paulovich, Amanda G.

2016-01-01

A major goal in cell signaling research is the quantification of phosphorylation pharmacodynamics following perturbations. Traditional methods of studying cellular phospho-signaling measure one analyte at a time with poor standardization, rendering them inadequate for interrogating network biology and contributing to the irreproducibility of preclinical research. In this study, we test the feasibility of circumventing these issues by coupling immobilized metal affinity chromatography (IMAC)-based enrichment of phosphopeptides with targeted, multiple reaction monitoring (MRM) mass spectrometry to achieve precise, specific, standardized, multiplex quantification of phospho-signaling responses. A multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay targeting phospho-analytes responsive to DNA damage was configured, analytically characterized, and deployed to generate phospho-pharmacodynamic curves from primary and immortalized human cells experiencing genotoxic stress. The multiplexed assays demonstrated linear ranges of ≥3 orders of magnitude, median lower limit of quantification of 0.64 fmol on column, median intra-assay variability of 9.3%, median inter-assay variability of 12.7%, and median total CV of 16.0%. The multiplex immobilized metal affinity chromatography- multiple reaction monitoring assay enabled robust quantification of 107 DNA damage-responsive phosphosites from human cells following DNA damage. The assays have been made publicly available as a resource to the community. The approach is generally applicable, enabling wide interrogation of signaling networks. PMID:26621847

Citizen Sensors for SHM: Use of Accelerometer Data from Smartphones

PubMed Central

Feng, Maria; Fukuda, Yoshio; Mizuta, Masato; Ozer, Ekin

2015-01-01

Ubiquitous smartphones have created a significant opportunity to form a low-cost wireless Citizen Sensor network and produce big data for monitoring structural integrity and safety under operational and extreme loads. Such data are particularly useful for rapid assessment of structural damage in a large urban setting after a major event such as an earthquake. This study explores the utilization of smartphone accelerometers for measuring structural vibration, from which structural health and post-event damage can be diagnosed. Widely available smartphones are tested under sinusoidal wave excitations with frequencies in the range relevant to civil engineering structures. Large-scale seismic shaking table tests, observing input ground motion and response of a structural model, are carried out to evaluate the accuracy of smartphone accelerometers under operational, white-noise and earthquake excitations of different intensity. Finally, the smartphone accelerometers are tested on a dynamically loaded bridge. The extensive experiments show satisfactory agreements between the reference and smartphone sensor measurements in both time and frequency domains, demonstrating the capability of the smartphone sensors to measure structural responses ranging from low-amplitude ambient vibration to high-amplitude seismic response. Encouraged by the results of this study, the authors are developing a citizen-engaging and data-analytics crowdsourcing platform towards a smartphone-based Citizen Sensor network for structural health monitoring and post-event damage assessment applications. PMID:25643056

Integrative proteome analysis of Brachypodium distachyon roots and leaves reveals a synergetic responsive network under H2O2 stress.

PubMed

Bian, Yan-Wei; Lv, Dong-Wen; Cheng, Zhi-Wei; Gu, Ai-Qin; Cao, Hui; Yan, Yue-Ming

2015-10-14

The plant oxidative stress response is vital for defense against various abiotic and biotic stresses. In this study, ultrastructural changes and the proteomic response to H2O2 stress in roots and leaves of the model plant Brachypodium distachyon were studied. Transmission electron microscopy (TEM) showed that the ultrastructural damage in roots was more serious than in leaves. Particularly, the ultrastructures of organelles and the nucleus in root tip cells were damaged, leading to the inhibition of normal biological activities of roots, which then spread throughout the plant. Based on two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF-MS, 84 and 53 differentially accumulated protein (DAP) spots representing 75 and 45 unique proteins responsive to H2O2 stress in roots and leaves, respectively, were identified. These protein species were mainly involved in signal transduction, energy metabolism, redox homeostasis/stress defense, protein folding/degradation, and cell wall/cell structure. Interestingly, two 14-3-3 proteins (GF14-B and GF14-D) were identified as DAPs in both roots and leaves. Protein-protein interaction (PPI) analysis revealed a synergetic H2O2-responsive network. Copyright © 2015 Elsevier B.V. All rights reserved.

The Fanconi anemia protein interaction network: casting a wide net.

PubMed

Rego, Meghan A; Kolling, Frederick W; Howlett, Niall G

2009-07-31

It has long been hypothesized that a defect in the repair of damaged DNA is central to the etiology of Fanconi anemia (FA). Indeed, an increased sensitivity of FA patient-derived cells to the lethal effects of various forms of DNA damaging agents was described over three decades ago [A.J. Fornace, Jr., J.B. Little, R.R. Weichselbaum, DNA repair in a Fanconi's anemia fibroblast cell strain, Biochim. Biophys. Acta 561 (1979) 99-109; Y. Fujiwara, M. Tatsumi, Repair of mitomycin C damage to DNA in mammalian cells and its impairment in Fanconi's anemia cells, Biochem. Biophys. Res. Commun. 66 (1975) 592-598; A.J. Rainbow, M. Howes, Defective repair of ultraviolet- and gamma-ray-damaged DNA in Fanconi's anaemia, Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 31 (1977) 191-195]. Furthermore, the cytological hallmark of FA, the DNA crosslink-induced radial chromosome formation, exemplifies an innate impairment in the repair of these particularly cytotoxic DNA lesions [A.D. Auerbach, Fanconi anemia diagnosis and the diepoxybutane (DEB) test, Exp. Hematol. 21 (1993) 731-733]. Precisely defining the collective role of the FA proteins in DNA repair, however, continues to be one of the most enigmatic and challenging questions in the FA field. The first six identified FA proteins (A, C, E, F, G, and D2) harbored no recognizable enzymatic features, precluding association with a specific metabolic process. Consequently, our knowledge of the role of the FA proteins in the DNA damage response has been gleaned primarily through biochemical association studies with non-FA proteins. Here, we provide a chronological discourse of the major FA protein interaction network discoveries, with particular emphasis on the DNA damage response, that have defined our current understanding of the molecular basis of FA.

A theory for fracture of polymeric gels

NASA Astrophysics Data System (ADS)

Mao, Yunwei; Anand, Lallit

2018-06-01

A polymeric gel is a cross-linked polymer network swollen with a solvent. If the concentration of the solvent or the deformation is increased to substantial levels, especially in the presence of flaws, then the gel may rupture. Although various theoretical aspects of coupling of fluid permeation with large deformation of polymeric gels are reasonably well-understood and modeled in the literature, the understanding and modeling of the effects of fluid diffusion on the damage and fracture of polymeric gels is still in its infancy. In this paper we formulate a thermodynamically-consistent theory for fracture of polymeric gels - a theory which accounts for the coupled effects of fluid diffusion, large deformations, damage, and also the gradient effects of damage. The particular constitutive equations for fracture of a gel proposed in our paper, contain two essential new ingredients: (i) Our constitutive equation for the change in free energy of a polymer network accounts for not only changes in the entropy, but also changes in the internal energy due the stretching of the Kuhn segments of the polymer chains in the network. (ii) The damage and failure of the polymer network is taken to occur by chain-scission, a process which is driven by the changes in the internal energy of the stretched polymer chains in the network, and not directly by changes in the configurational entropy of the polymer chains. The theory developed in this paper is numerically implemented in an open-source finite element code MOOSE, by writing our own application. Using this simulation capability we report on our study of the fracture of a polymeric gel, and some interesting phenomena which show the importance of the diffusion of the fluid on fracture response of the gel are highlighted.

Network Meta-Analysis on the Effects of DNA Damage Response-Related Gene Mutations on Overall Survival of Breast Cancer Based on TCGA Database.

PubMed

Liu, Chang; Chang, Hong; Li, Xiao-Han; Qi, Ya-Fei; Wang, Jin-Ou; Zhang, Ying; Yang, Xiang-Hong

2017-12-01

The study was conducted for comparing the effects of 12 DNA damage response gene mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1, and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We searched the Cancer Genome Atlas (TCGA) database from inception to September 2016. Studies that investigated the association between 12 DNA damage responses related genes and BC consolidated into this Network meta-analysis, by comparing directly or indirectly to evaluate the hazard rate (HR) value and the surface under the cumulative sequence ranking curves (SUCRA). In total four articles were involved. Our results demonstrated 12 DNA damage response gene mutations were associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6-26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0; BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR = 11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI = 2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0; PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA results revealed that the mutation of MDC1 gene was related to the worst prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene mutations were associated to the poor prognosis in patients with BC and the BC patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118: 4728-4734, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DDRprot: a database of DNA damage response-related proteins.

PubMed

Andrés-León, Eduardo; Cases, Ildefonso; Arcas, Aida; Rojas, Ana M

2016-01-01

The DNA Damage Response (DDR) signalling network is an essential system that protects the genome's integrity. The DDRprot database presented here is a resource that integrates manually curated information on the human DDR network and its sub-pathways. For each particular DDR protein, we present detailed information about its function. If involved in post-translational modifications (PTMs) with each other, we depict the position of the modified residue/s in the three-dimensional structures, when resolved structures are available for the proteins. All this information is linked to the original publication from where it was obtained. Phylogenetic information is also shown, including time of emergence and conservation across 47 selected species, family trees and sequence alignments of homologues. The DDRprot database can be queried by different criteria: pathways, species, evolutionary age or involvement in (PTM). Sequence searches using hidden Markov models can be also used.Database URL: http://ddr.cbbio.es. © The Author(s) 2016. Published by Oxford University Press.

Optical Calibration Process Developed for Neural-Network-Based Optical Nondestructive Evaluation Method

NASA Technical Reports Server (NTRS)

Decker, Arthur J.

2004-01-01

A completely optical calibration process has been developed at Glenn for calibrating a neural-network-based nondestructive evaluation (NDE) method. The NDE method itself detects very small changes in the characteristic patterns or vibration mode shapes of vibrating structures as discussed in many references. The mode shapes or characteristic patterns are recorded using television or electronic holography and change when a structure experiences, for example, cracking, debonds, or variations in fastener properties. An artificial neural network can be trained to be very sensitive to changes in the mode shapes, but quantifying or calibrating that sensitivity in a consistent, meaningful, and deliverable manner has been challenging. The standard calibration approach has been difficult to implement, where the response to damage of the trained neural network is compared with the responses of vibration-measurement sensors. In particular, the vibration-measurement sensors are intrusive, insufficiently sensitive, and not numerous enough. In response to these difficulties, a completely optical alternative to the standard calibration approach was proposed and tested successfully. Specifically, the vibration mode to be monitored for structural damage was intentionally contaminated with known amounts of another mode, and the response of the trained neural network was measured as a function of the peak-to-peak amplitude of the contaminating mode. The neural network calibration technique essentially uses the vibration mode shapes of the undamaged structure as standards against which the changed mode shapes are compared. The published response of the network can be made nearly independent of the contaminating mode, if enough vibration modes are used to train the net. The sensitivity of the neural network can be adjusted for the environment in which the test is to be conducted. The response of a neural network trained with measured vibration patterns for use on a vibration isolation table in the presence of various sources of laboratory noise is shown. The output of the neural network is called the degradable classification index. The curve was generated by a simultaneous comparison of means, and it shows a peak-to-peak sensitivity of about 100 nm. The following graph uses model generated data from a compressor blade to show that much higher sensitivities are possible when the environment can be controlled better. The peak-to-peak sensitivity here is about 20 nm. The training procedure was modified for the second graph, and the data were subjected to an intensity-dependent transformation called folding. All the measurements for this approach to calibration were optical. The peak-to-peak amplitudes of the vibration modes were measured using heterodyne interferometry, and the modes themselves were recorded using television (electronic) holography.

Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis

PubMed Central

Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-hua; Xue, Dongbo

2017-01-01

Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma. PMID:28355233

ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.

PubMed

Berger, N Daniel; Stanley, Fintan K T; Moore, Shaun; Goodarzi, Aaron A

2017-10-05

Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

Real-Time Continuous Response Spectra Exceedance Calculation

NASA Astrophysics Data System (ADS)

Vernon, Frank; Harvey, Danny; Lindquist, Kent; Franke, Mathias

2017-04-01

A novel approach is presented for near real-time earthquake alarms for critical structures at distributed locations using real-time estimation of response spectra obtained from near free-field motions. Influential studies dating back to the 1980s identified spectral response acceleration as a key ground motion characteristic that correlates well with observed damage in structures. Thus, monitoring and reporting on exceedance of spectra-based thresholds are useful tools for assessing the potential for damage to facilities or multi-structure campuses based on input ground motions only. With as little as one strong-motion station per site, this scalable approach can provide rapid alarms on the damage status of remote towns, critical infrastructure (e.g., hospitals, schools) and points of interests (e.g., bridges) for a very large number of locations enabling better rapid decision making during critical and difficult immediate post-earthquake response actions. Real-time calculation of PSA exceedance and alarm dissemination are enabled with Bighorn, a module included in the Antelope software package that combines real-time spectral monitoring and alarm capabilities with a robust built-in web display server. Examples of response spectra from several M 5 events recorded by the ANZA seismic network in southern California will be presented.

Cellular responses and gene expression profile changes due to bleomycin-induced DNA damage in human fibroblasts in space

PubMed Central

Kidane, Yared; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Ramesh, Govindarajan; Rohde, Larry; Wu, Honglu

2017-01-01

Living organisms in space are constantly exposed to radiation, toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage is essential for assessing the radiation risk for astronauts and the mutation rate in microorganisms. In a study conducted on the International Space Station, confluent human fibroblasts in culture were treated with bleomycin for three hours in the true microgravity environment. The degree of DNA damage was quantified by immunofluorescence staining for γ-H2AX, which is manifested in three types of staining patterns. Although similar percentages of these types of patterns were found between flight and ground cells, there was a slight shift in the distribution of foci counts in the flown cells with countable numbers of γ-H2AX foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. We also performed a microarray analysis of gene expressions in response to bleomycin treatment. A qualitative comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. The microarray data was confirmed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly upregulated in both flight and ground cells after bleomycin treatment. Our results suggest that whether microgravity affects DNA damage response in space can be dependent on the cell type and cell growth condition. PMID:28248986

Differential proteomic analysis reveals sequential heat stress-responsive regulatory network in radish (Raphanus sativus L.) taproot.

PubMed

Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-05-01

Differential abundance protein species (DAPS) involved in reducing damage and enhancing thermotolerance in radish were firstly identified. Proteomic analysis and omics association analysis revealed a HS-responsive regulatory network in radish. Heat stress (HS) is a major destructive factor influencing radish production and supply in summer, for radish is a cool season vegetable crop being susceptible to high temperature. In this study, the proteome changes of radish taproots under 40 °C treatment at 0 h (Control), 12 h (Heat12) and 24 h (Heat24) were analyzed using iTRAQ (Isobaric Tag for Relative and Absolute Quantification) approach. In total, 2258 DAPS representing 1542 differentially accumulated uniprotein species which respond to HS were identified. A total of 604, 910 and 744 DAPS was detected in comparison of Control vs. Heat12, Control vs. Heat24, and Heat12 vs. Heat24, respectively. Gene ontology and pathway analysis showed that annexin, ubiquitin-conjugating enzyme, ATP synthase, heat shock protein (HSP) and other stress-related proteins were predominately enriched in signal transduction, stress and defense pathways, photosynthesis and energy metabolic pathways, working cooperatively to reduce stress-induced damage in radish. Based on iTRAQ combined with the transcriptomics analysis, a schematic model of a sequential HS-responsive regulatory network was proposed. The initial sensing of HS occurred at the plasma membrane, and then key components of stress signal transduction triggered heat-responsive genes in the plant protective metabolism to re-establish homeostasis and enhance thermotolerance. These results provide new insights into characteristics of HS-responsive DAPS and facilitate dissecting the molecular mechanisms underlying heat tolerance in radish and other root crops.

A ChIP-chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response.

PubMed

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-03-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP-chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response.

A ChIP–chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response

PubMed Central

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-01-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP–chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response. PMID:19129219

An Adaptive Critic Approach to Reference Model Adaptation

NASA Technical Reports Server (NTRS)

Krishnakumar, K.; Limes, G.; Gundy-Burlet, K.; Bryant, D.

2003-01-01

Neural networks have been successfully used for implementing control architectures for different applications. In this work, we examine a neural network augmented adaptive critic as a Level 2 intelligent controller for a C- 17 aircraft. This intelligent control architecture utilizes an adaptive critic to tune the parameters of a reference model, which is then used to define the angular rate command for a Level 1 intelligent controller. The present architecture is implemented on a high-fidelity non-linear model of a C-17 aircraft. The goal of this research is to improve the performance of the C-17 under degraded conditions such as control failures and battle damage. Pilot ratings using a motion based simulation facility are included in this paper. The benefits of using an adaptive critic are documented using time response comparisons for severe damage situations.

A study of two unsupervised data driven statistical methodologies for detecting and classifying damages in structural health monitoring

NASA Astrophysics Data System (ADS)

Tibaduiza, D.-A.; Torres-Arredondo, M.-A.; Mujica, L. E.; Rodellar, J.; Fritzen, C.-P.

2013-12-01

This article is concerned with the practical use of Multiway Principal Component Analysis (MPCA), Discrete Wavelet Transform (DWT), Squared Prediction Error (SPE) measures and Self-Organizing Maps (SOM) to detect and classify damages in mechanical structures. The formalism is based on a distributed piezoelectric active sensor network for the excitation and detection of structural dynamic responses. Statistical models are built using PCA when the structure is known to be healthy either directly from the dynamic responses or from wavelet coefficients at different scales representing Time-frequency information. Different damages on the tested structures are simulated by adding masses at different positions. The data from the structure in different states (damaged or not) are then projected into the different principal component models by each actuator in order to obtain the input feature vectors for a SOM from the scores and the SPE measures. An aircraft fuselage from an Airbus A320 and a multi-layered carbon fiber reinforced plastic (CFRP) plate are used as examples to test the approaches. Results are presented, compared and discussed in order to determine their potential in structural health monitoring. These results showed that all the simulated damages were detectable and the selected features proved capable of separating all damage conditions from the undamaged state for both approaches.

Lamb wave based damage detection using Matching Pursuit and Support Vector Machine classifier

NASA Astrophysics Data System (ADS)

Agarwal, Sushant; Mitra, Mira

2014-03-01

In this paper, the suitability of using Matching Pursuit (MP) and Support Vector Machine (SVM) for damage detection using Lamb wave response of thin aluminium plate is explored. Lamb wave response of thin aluminium plate with or without damage is simulated using finite element. Simulations are carried out at different frequencies for various kinds of damage. The procedure is divided into two parts - signal processing and machine learning. Firstly, MP is used for denoising and to maintain the sparsity of the dataset. In this study, MP is extended by using a combination of time-frequency functions as the dictionary and is deployed in two stages. Selection of a particular type of atoms lead to extraction of important features while maintaining the sparsity of the waveform. The resultant waveform is then passed as input data for SVM classifier. SVM is used to detect the location of the potential damage from the reduced data. The study demonstrates that SVM is a robust classifier in presence of noise and more efficient as compared to Artificial Neural Network (ANN). Out-of-sample data is used for the validation of the trained and tested classifier. Trained classifiers are found successful in detection of the damage with more than 95% detection rate.

Combination of DTI and fMRI reveals the white matter changes correlating with the decline of default-mode network activity in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Wu, Xianjun; Di, Qian; Li, Yao; Zhao, Xiaojie

2009-02-01

Recently, evidences from fMRI studies have shown that there was decreased activity among the default-mode network in Alzheimer's disease (AD), and DTI researches also demonstrated that demyelinations exist in white matter of AD patients. Therefore, combining these two MRI methods may help to reveal the relationship between white matter damages and alterations of the resting state functional connectivity network. In the present study, we tried to address this issue by means of correlation analysis between DTI and resting state fMRI images. The default-mode networks of AD and normal control groups were compared to find the areas with significantly declined activity firstly. Then, the white matter regions whose fractional anisotropy (FA) value correlated with this decline were located through multiple regressions between the FA values and the BOLD response of the default networks. Among these correlating white matter regions, those whose FA values also declined were found by a group comparison between AD patients and healthy elderly control subjects. Our results showed that the areas with decreased activity among default-mode network included left posterior cingulated cortex (PCC), left medial temporal gyrus et al. And the damaged white matter areas correlated with the default-mode network alterations were located around left sub-gyral temporal lobe. These changes may relate to the decreased connectivity between PCC and medial temporal lobe (MTL), and thus correlate with the deficiency of default-mode network activity.

Gene regulatory network of unfolded protein response genes in endoplasmic reticulum stress.

PubMed

Takayanagi, Sayuri; Fukuda, Riga; Takeuchi, Yuuki; Tsukada, Sakiko; Yoshida, Kenichi

2013-01-01

In the endoplasmic reticulum (ER), secretory and membrane proteins are properly folded and modified, and the failure of these processes leads to ER stress. At the same time, unfolded protein response (UPR) genes are activated to maintain homeostasis. Despite the thorough characterization of the individual gene regulation of UPR genes to date, further investigation of the mutual regulation among UPR genes is required to understand the complex mechanism underlying the ER stress response. In this study, we aimed to reveal a gene regulatory network formed by UPR genes, including immunoglobulin heavy chain-binding protein (BiP), X-box binding protein 1 (XBP1), C/EBP [CCAAT/enhancer-binding protein]-homologous protein (CHOP), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring 1 (IRE1), activating transcription factor 6 (ATF6), and ATF4. For this purpose, we focused on promoter-luciferase reporters for BiP, XBP1, and CHOP genes, which bear an ER stress response element (ERSE), and p5 × ATF6-GL3, which bears an unfolded protein response element (UPRE). We demonstrated that the luciferase activities of the BiP and CHOP promoters were upregulated by all the UPR genes, whereas those of the XBP1 promoter and p5 × ATF6-GL3 were upregulated by all the UPR genes except for BiP, CHOP, and ATF4 in HeLa cells. Therefore, an ERSE- and UPRE-centered gene regulatory network of UPR genes could be responsible for the robustness of the ER stress response. Finally, we revealed that BiP protein was degraded when cells were treated with DNA-damaging reagents, such as etoposide and doxorubicin; this finding suggests that the expression level of BiP is tightly regulated at the post-translational level, rather than at the transcriptional level, in the presence of DNA damage.

Intelligent-based Structural Damage Detection Model

NASA Astrophysics Data System (ADS)

Lee, Eric Wai Ming; Yu, Kin Fung

2010-05-01

This paper presents the application of a novel Artificial Neural Network (ANN) model for the diagnosis of structural damage. The ANN model, denoted as the GRNNFA, is a hybrid model combining the General Regression Neural Network Model (GRNN) and the Fuzzy ART (FA) model. It not only retains the important features of the GRNN and FA models (i.e. fast and stable network training and incremental growth of network structure) but also facilitates the removal of the noise embedded in the training samples. Structural damage alters the stiffness distribution of the structure and so as to change the natural frequencies and mode shapes of the system. The measured modal parameter changes due to a particular damage are treated as patterns for that damage. The proposed GRNNFA model was trained to learn those patterns in order to detect the possible damage location of the structure. Simulated data is employed to verify and illustrate the procedures of the proposed ANN-based damage diagnosis methodology. The results of this study have demonstrated the feasibility of applying the GRNNFA model to structural damage diagnosis even when the training samples were noise contaminated.

Enhancement of the Feature Extraction Capability in Global Damage Detection Using Wavelet Theory

NASA Technical Reports Server (NTRS)

Saleeb, Atef F.; Ponnaluru, Gopi Krishna

2006-01-01

The main objective of this study is to assess the specific capabilities of the defect energy parameter technique for global damage detection developed by Saleeb and coworkers. The feature extraction is the most important capability in any damage-detection technique. Features are any parameters extracted from the processed measurement data in order to enhance damage detection. The damage feature extraction capability was studied extensively by analyzing various simulation results. The practical significance in structural health monitoring is that the detection at early stages of small-size defects is always desirable. The amount of changes in the structure's response due to these small defects was determined to show the needed level of accuracy in the experimental methods. The arrangement of fine/extensive sensor network to measure required data for the detection is an "unlimited" ability, but there is a difficulty to place extensive number of sensors on a structure. Therefore, an investigation was conducted using the measurements of coarse sensor network. The white and the pink noises, which cover most of the frequency ranges that are typically encountered in the many measuring devices used (e.g., accelerometers, strain gauges, etc.) are added to the displacements to investigate the effect of noisy measurements in the detection technique. The noisy displacements and the noisy damage parameter values are used to study the signal feature reconstruction using wavelets. The enhancement of the feature extraction capability was successfully achieved by the wavelet theory.

Alkylation Damage by Lipid Electrophiles Targets Functional Protein Systems*

PubMed Central

Codreanu, Simona G.; Ullery, Jody C.; Zhu, Jing; Tallman, Keri A.; Beavers, William N.; Porter, Ned A.; Marnett, Lawrence J.; Zhang, Bing; Liebler, Daniel C.

2014-01-01

Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions. PMID:24429493

Reflexive composites: self-healing composite structures

NASA Astrophysics Data System (ADS)

Margraf, Thomas W., Jr.; Barnell, Thomas J.; Havens, Ernie; Hemmelgarn, Christopher D.

2008-03-01

Cornerstone Research Group Inc. has developed reflexive composites achieving increased vehicle survivability through integrated structural awareness and responsiveness to damage. Reflexive composites can sense damage through integrated piezoelectric sensing networks and respond to damage by heating discrete locations to activate the healable polymer matrix in areas of damage. The polymer matrix is a modified thermoset shape memory polymer that heals based on phenomena known as reptation. In theory, the reptation healing phenomena should occur in microseconds; however, during experimentation, it has been observed that to maximize healing and restore up to 85 % of mechanical properties a healing cycle of at least three minutes is required. This paper will focus on work conducted to determine the healing mechanisms at work in CRG's reflexive composites, the optimal healing cycles, and an explanation of the difference between the reptation model and actual healing times.

Towards Integrated Marmara Strong Motion Network

NASA Astrophysics Data System (ADS)

Durukal, E.; Erdik, M.; Safak, E.; Ansal, A.; Ozel, O.; Alcik, H.; Mert, A.; Kafadar, N.; Korkmaz, A.; Kurtulus, A.

2009-04-01

Istanbul has a 65% chance of having a magnitude 7 or above earthquake within the next 30 years. As part of the preparations for the future earthquake, strong motion networks have been installed in and around Istanbul. The Marmara Strong Motion Network, operated by the Department of Earthquake Engineering of Kandilli Observatory and Earthquake Research Institute, encompasses permanent systems outlined below. It is envisaged that the networks will be run by a single entity responsible for technical management and maintanence, as well as for data management, archiving and dissemination through dedicated web-based interfaces. • Istanbul Earthquake Rapid Response and Early Warning System - IERREWS (one hundred 18-bit accelerometers for rapid response; ten 24-bit accelerometers for early warning) • IGDAŞ Gas Shutoff Network (100 accelerometers to be installed in 2010 and integrated with IERREWS) • Structural Monitoring Arrays - Fatih Sultan Mehmet Suspension Bridge (1200m-long suspension bridge across the Bosphorus, five 3-component accelerometers + GPS sensors) - Hagia Sophia Array (1500-year-old historical edifice, 9 accelerometers) - Süleymaniye Mosque Array (450-year-old historical edifice,9 accelerometers) - Fatih Mosque Array (237-year-old historical edifice, 9 accelerometers) - Kanyon Building Array (high-rise office building, 5 accelerometers) - Isbank Tower Array (high-rise office building, 5 accelerometers) - ENRON Array (power generation facility, 4 acelerometers) - Mihrimah Sultan Mosque Array (450-year-old historical edifice,9 accelerometers + tiltmeters, to be installed in 2009) - Sultanahmet Mosque Array, (390-year-old historical edifice, 9 accelerometers + tiltmeters, to be installed in 2009) • Special Arrays - Atakoy Vertical Array (four 3-component accelerometers at 25, 50, 75, and 150 m depths) - Marmara Tube Tunnel (1400 m long submerged tunnel, 128 ch. accelerometric data, 24 ch. strain data, to be installed in 2010) - Air-Force Academy Array (72 ch. dense accelerometric array to be installed in 2010) - Gemlik Array (a dense basin array of 8 stations, to be installed in 2010) The objectives of these systems and networks are: (1) to produce rapid earthquake intensity, damage and loss assessment information after an earthquake (in the case of IERREWS), (2) to monitor conditions of structural systems, (3) to develop real-time data processing, analysis, and damage detection and location tools (in the case of structural networks) after an extreme event, (4) to assess spatial properties of strong ground motion and ground strain, and to characterise basin response (in the case of special arrays), (5) to investigate site response and wave propagation (in the case of vertical array). Ground motion data obtained from these strong motion networks have and are being used for investigations of attenuation, spatial variation (coherence), simulation benchmarking, source modeling, site response, seismic microzonation, system identification and structural model verification and structural health control. In addition to the systems and networks outlined above there are two temporary networks: KIMNET - a dense urban noise and microtremor network consisting of 50 broadband stations expected to be operational in mid 2009, and SOSEWIN - a 20-station, self-organizing structural integrated array at Ataköy in Istanbul.

A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies.

PubMed

Geminiani, Alice; Casellato, Claudia; Antonietti, Alberto; D'Angelo, Egidio; Pedrocchi, Alessandra

2018-06-01

The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies.

Impact Factors and Risk Analysis of Tropical Cyclones on a Highway Network.

PubMed

Yang, Saini; Hu, Fuyu; Jaeger, Carlo

2016-02-01

Coastal areas typically have high social and economic development and are likely to suffer huge losses due to tropical cyclones. These cyclones have a great impact on the transportation network, but there have been a limited number of studies about tropical-cyclone-induced transportation network functional damages, especially in Asia. This study develops an innovative measurement and analytical tool for highway network functional damage and risk in the context of a tropical cyclone, with which we explored the critical spatial characteristics of tropical cyclones with regard to functional damage to a highway network by developing linear regression models to quantify their relationship. Furthermore, we assessed the network's functional risk and calculated the return periods under different damage levels. In our analyses, we consider the real-world highway network of Hainan province, China. Our results illustrate that the most important spatial characteristics were location (in particular, the midlands), travel distance, landfalling status, and origin coordinates. However, the trajectory direction did not obviously affect the results. Our analyses indicate that the highway network of Hainan province may suffer from a 90% functional damage scenario every 4.28 years. These results have critical policy implications for the transport sector in reference to emergency planning and disaster reduction. © 2015 Society for Risk Analysis.

DiffNet: automatic differential functional summarization of dE-MAP networks.

PubMed

Seah, Boon-Siew; Bhowmick, Sourav S; Dewey, C Forbes

2014-10-01

The study of genetic interaction networks that respond to changing conditions is an emerging research problem. Recently, Bandyopadhyay et al. (2010) proposed a technique to construct a differential network (dE-MAPnetwork) from two static gene interaction networks in order to map the interaction differences between them under environment or condition change (e.g., DNA-damaging agent). This differential network is then manually analyzed to conclude that DNA repair is differentially effected by the condition change. Unfortunately, manual construction of differential functional summary from a dE-MAP network that summarizes all pertinent functional responses is time-consuming, laborious and error-prone, impeding large-scale analysis on it. To this end, we propose DiffNet, a novel data-driven algorithm that leverages Gene Ontology (go) annotations to automatically summarize a dE-MAP network to obtain a high-level map of functional responses due to condition change. We tested DiffNet on the dynamic interaction networks following MMS treatment and demonstrated the superiority of our approach in generating differential functional summaries compared to state-of-the-art graph clustering methods. We studied the effects of parameters in DiffNet in controlling the quality of the summary. We also performed a case study that illustrates its utility. Copyright © 2014 Elsevier Inc. All rights reserved.

The regulatory network analysis of long noncoding RNAs in human colorectal cancer.

PubMed

Zhang, Yuwei; Tao, Yang; Li, Yang; Zhao, Jinshun; Zhang, Lina; Zhang, Xiaohong; Dong, Changzheng; Xie, Yangyang; Dai, Xiaoyu; Zhang, Xinjun; Liao, Qi

2018-05-01

Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.

75 FR 49870 - Effects on Broadband Communications Networks of Damage to or Failure of Network Equipment or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-16

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Chapter I [PS Docket No. 10-92; DA 10-1357] Effects on Broadband Communications Networks of Damage to or Failure of Network Equipment or Severe Overload AGENCY: Federal Communications Commission ACTION: Proposed rule; extension of reply comment date. SUMMARY: This...

Novel self-sensing carbon nanotube-based composites for rehabilitation of structural steel members

NASA Astrophysics Data System (ADS)

Ahmed, Shafique; Doshi, Sagar; Schumacher, Thomas; Thostenson, Erik T.; McConnell, Jennifer

2016-02-01

Fatigue and fracture are among the most critical forms of damage in metal structures. Fatigue damage can initiate from microscopic defects (e.g., surface scratches, voids in welds, and internal defects) and initiate a crack. Under cyclic loading, these cracks can grow and reach a critical level to trigger fracture of the member which leads to compromised structural integrity and, in some cases, catastrophic failure of the entire structure. In our research, we are investigating a solution using carbon nanotube-based sensing composites, which have the potential to simultaneously rehabilitate and monitor fatigue-cracked structural members. These composites consist of a fiber-reinforced polymer (FRP) layer and a carbon nanotube-based sensing layer, which are integrated to form a novel structural self-sensing material. The sensing layer is composed of a non-woven aramid fabric that is coated with carbon nanotubes (CNT) to form an electrically conductive network that is extremely sensitive to detecting deformation as well as damage accumulation via changes in the resistance of the CNT network. In this paper, we introduce the sensing concept, describe the manufacturing of a model sensing prototype, and discuss a set of small-scale laboratory experiments to examine the load-carrying capacity and damage sensing response.

Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry Enables Multiplex, Quantitative Pharmacodynamic Studies of Phospho-Signaling*

PubMed Central

Whiteaker, Jeffrey R.; Zhao, Lei; Yan, Ping; Ivey, Richard G.; Voytovich, Uliana J.; Moore, Heather D.; Lin, Chenwei; Paulovich, Amanda G.

2015-01-01

In most cell signaling experiments, analytes are measured one Western blot lane at a time in a semiquantitative and often poorly specific manner, limiting our understanding of network biology and hindering the translation of novel therapeutics and diagnostics. We show the feasibility of using multiplex immuno-MRM for phospho-pharmacodynamic measurements, establishing the potential for rapid and precise quantification of cell signaling networks. A 69-plex immuno-MRM assay targeting the DNA damage response network was developed and characterized by response curves and determinations of intra- and inter-assay repeatability. The linear range was ≥3 orders of magnitude, the median limit of quantification was 2.0 fmol/mg, the median intra-assay variability was 10% CV, and the median interassay variability was 16% CV. The assay was applied in proof-of-concept studies to immortalized and primary human cells and surgically excised cancer tissues to quantify exposure–response relationships and the effects of a genomic variant (ATM kinase mutation) or pharmacologic (kinase) inhibitor. The study shows the utility of multiplex immuno-MRM for simultaneous quantification of phosphorylated and nonmodified peptides, showing feasibility for development of targeted assay panels to cell signaling networks. PMID:25987412

Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes.

PubMed

Sanchez-Alberola, Neus; Campoy, Susana; Barbé, Jordi; Erill, Ivan

2012-02-03

The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an essential role in these organisms and sheds light into the mechanisms of evolution of global transcriptional networks involved in adaptability and rapid response to environmental changes, suggesting that small chromosomes may act as evolutionary test beds for the rewiring of transcriptional networks.

RICHTER: A Smartphone Application for Rapid Collection of Geo-Tagged Pictures of Earthquake Damage

NASA Astrophysics Data System (ADS)

Skinnemoen, H.; Bossu, R.; Furuheim, K.; Bjorgo, E.

2010-12-01

RICHTER (Rapid geo-Images for Collaborative Help Targeting Earthquake Response) is a smartphone version of a professional application developed to provide high quality geo-tagged image communication over challenging network links, such as satellites and poor mobile links. Developed for Android mobile phones, it allows eyewitnesses to share their pictures of earthquake damage easily and without cost with the Euro-Mediterranean Seismological Centre (EMSC). The goal is to engage citizens in the collection of the most up-to-date visual information on local damage for improved rapid impact assessment. RICHTER integrates the innovative and award winning ASIGN protocol initially developed for satellite communication between cameras / computers / satcom terminals and servers at HQ. ASIGN is a robust and optimal image and video communication management solution for bandwidth-limited communication networks which was developed for use particularly in emergency and disaster situations. Contrary to a simple Multimedia Messaging System (MMS), RICHTER allows access to high definition images with embedded location information. Location is automatically assigned from either the internal GPS, derived from the mobile network (triangulation) or the current Wi-Fi domain, in that order, as this corresponds to the expected positioning accuracy. Pictures are compressed to 20-30KB of data typically for fast transfer and to avoid network overload. Full size images can be requested by the EMSC either fully automatically, or on a case-by-case basis, depending on the user preferences. ASIGN was initially developed in coordination with INMARSAT and the European Space Agency. It was used by the Rapid Mapping Unit of the United Nations notably for the damage assessment of the January 12, 2010 Haiti earthquake where more than 700 photos were collected. RICHTER will be freely distributed on the EMSC website to eyewitnesses in the event of significantly damaging earthquakes. The EMSC is the second most popular rapid earthquake information website after the USGS. Eyewitnesses of widely felt or damaging earthquakes usually arrive at the EMSC website within a couple of minutes of the event’s occurrence, making it an ideal site for rapid and targeted dissemination. RICHTER is the latest development in a series of internet applications designed to harness the collective power of citizens to provide rapid earthquake damage analysis reports. This strategy is called “Citizen Seismology,” and includes online macroseismic questionnaires available in 32 languages, real time analysis of EMSC website traffic to map felt and damaged areas from localized increases - or significant absence - of visitors after an earthquake occurrence, collection of pictures, mobile-phone targeted macroseismic questionnaires in which damage-representative thumbnail images replace textual questionnaires, as well as a citizen-operated network of embedded laptop motion sensors. Future developments for RICHTER under consideration include the collection of video and harnessing the embedded motion sensors to capture seismic activity.

Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970

PubMed Central

Boucher, Diane M.; Eustace, Brenda; Gu, Yong; Hare, Brian; Johnson, Mac A.; Milton, Sean; Murphy, Cheryl E.; Takemoto, Darin; Tolman, Crystal; Wood, Mark; Charlton, Peter; Charrier, Jean-Damien; Furey, Brinley; Golec, Julian; Reaper, Philip M.; Pollard, John R.

2014-01-01

Platinum-based DNA-damaging chemotherapy is standard-of-care for most patients with lung cancer but outcomes remain poor. This has been attributed, in part, to the highly effective repair network known as the DNA-damage response (DDR). ATR kinase is a critical regulator of this pathway, and its inhibition has been shown to sensitize some cancer, but not normal, cells in vitro to DNA damaging agents. However, there are limited in vivo proof-of-concept data for ATR inhibition. To address this we profiled VX-970, the first clinical ATR inhibitor, in a series of in vitro and in vivo lung cancer models and compared it with an inhibitor of the downstream kinase Chk1. VX-970 markedly sensitized a large proportion of a lung cancer cell line and primary tumor panel in vitro to multiple DNA damaging drugs with clear differences to Chk1 inhibition observed. In vivo VX-970 blocked ATR activity in tumors and dramatically enhanced the efficacy of cisplatin across a panel of patient derived primary lung xenografts. The combination led to complete tumor growth inhibition in three cisplatin-insensitive models and durable tumor regression in a cisplatin-sensitive model. These data provide a strong rationale for the clinical evaluation of VX-970 in lung cancer patients. PMID:25010037

Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970.

PubMed

Hall, Amy B; Newsome, Dave; Wang, Yuxin; Boucher, Diane M; Eustace, Brenda; Gu, Yong; Hare, Brian; Johnson, Mac A; Milton, Sean; Murphy, Cheryl E; Takemoto, Darin; Tolman, Crystal; Wood, Mark; Charlton, Peter; Charrier, Jean-Damien; Furey, Brinley; Golec, Julian; Reaper, Philip M; Pollard, John R

2014-07-30

Platinum-based DNA-damaging chemotherapy is standard-of-care for most patients with lung cancer but outcomes remain poor. This has been attributed, in part, to the highly effective repair network known as the DNA-damage response (DDR). ATR kinase is a critical regulator of this pathway, and its inhibition has been shown to sensitize some cancer, but not normal, cells in vitro to DNA damaging agents. However, there are limited in vivo proof-of-concept data for ATR inhibition. To address this we profiled VX-970, the first clinical ATR inhibitor, in a series of in vitro and in vivo lung cancer models and compared it with an inhibitor of the downstream kinase Chk1. VX-970 markedly sensitized a large proportion of a lung cancer cell line and primary tumor panel in vitro to multiple DNA damaging drugs with clear differences to Chk1 inhibition observed. In vivo VX-970 blocked ATR activity in tumors and dramatically enhanced the efficacy of cisplatin across a panel of patient derived primary lung xenografts. The combination led to complete tumor growth inhibition in three cisplatin-insensitive models and durable tumor regression in a cisplatin-sensitive model. These data provide a strong rationale for the clinical evaluation of VX-970 in lung cancer patients.

Damage and Loss Estimation for Natural Gas Networks: The Case of Istanbul

NASA Astrophysics Data System (ADS)

Çaktı, Eser; Hancılar, Ufuk; Şeşetyan, Karin; Bıyıkoǧlu, Hikmet; Şafak, Erdal

2017-04-01

Natural gas networks are one of the major lifeline systems to support human, urban and industrial activities. The continuity of gas supply is critical for almost all functions of modern life. Under natural phenomena such as earthquakes and landslides the damages to the system elements may lead to explosions and fires compromising human life and damaging physical environment. Furthermore, the disruption in the gas supply puts human activities at risk and also results in economical losses. This study is concerned with the performance of one of the largest natural gas distribution systems in the world. Physical damages to Istanbul's natural gas network are estimated under the most recent probabilistic earthquake hazard models available, as well as under simulated ground motions from physics based models. Several vulnerability functions are used in modelling damages to system elements. A first-order assessment of monetary losses to Istanbul's natural gas distribution network is also attempted.

Stromal regulation of vessel stability by MMP14 and TGFβ

PubMed Central

Sounni, Nor E.; Dehne, Kerstin; van Kempen, Leon; Egeblad, Mikala; Affara, Nesrine I.; Cuevas, Ileana; Wiesen, Jane; Junankar, Simon; Korets, Lidiya; Lee, Jake; Shen, Jennifer; Morrison, Charlotte J.; Overall, Christopher M.; Krane, Stephen M.; Werb, Zena; Boudreau, Nancy; Coussens, Lisa M.

2010-01-01

Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) and transforming growth factor beta 1 (TGFβ1). Whereas plasma proteins rapidly extravasate out of vasculature in wild-type mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGFβ1, or an activin-like kinase 5 (ALK5) inhibitor significantly enhanced vessel leakage. By contrast, in a mouse model of age-related dermal fibrosis, where MMP14 activity and TGFβ bioavailability are chronically elevated, or in mice that ectopically express TGFβ in the epidermis, cutaneous vessels are resistant to acute leakage. Characteristic responses to tissue damage are reinstated if the fibrotic mice are pretreated with metalloproteinase inhibitors or TGFβ signaling antagonists. Neoplastic tissues, however, are in a constant state of tissue damage and exhibit altered hemodynamics owing to hyperleaky angiogenic vasculature. In two distinct transgenic mouse tumor models, inhibition of ALK5 further enhanced vascular leakage into the interstitium and facilitated increased delivery of high molecular weight compounds into premalignant tissue and tumors. Taken together, these data define a central pathway involving MMP14 and TGFβ that mediates vessel stability and vascular response to tissue injury. Antagonists of this pathway could be therapeutically exploited to improve the delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery. PMID:20223936

A topology visualization early warning distribution algorithm for large-scale network security incidents.

PubMed

He, Hui; Fan, Guotao; Ye, Jianwei; Zhang, Weizhe

2013-01-01

It is of great significance to research the early warning system for large-scale network security incidents. It can improve the network system's emergency response capabilities, alleviate the cyber attacks' damage, and strengthen the system's counterattack ability. A comprehensive early warning system is presented in this paper, which combines active measurement and anomaly detection. The key visualization algorithm and technology of the system are mainly discussed. The large-scale network system's plane visualization is realized based on the divide and conquer thought. First, the topology of the large-scale network is divided into some small-scale networks by the MLkP/CR algorithm. Second, the sub graph plane visualization algorithm is applied to each small-scale network. Finally, the small-scale networks' topologies are combined into a topology based on the automatic distribution algorithm of force analysis. As the algorithm transforms the large-scale network topology plane visualization problem into a series of small-scale network topology plane visualization and distribution problems, it has higher parallelism and is able to handle the display of ultra-large-scale network topology.

Introducing ShakeMap to potential users in Puerto Rico using scenarios of damaging historical and probable earthquakes

NASA Astrophysics Data System (ADS)

Huerfano, V. A.; Cua, G.; von Hillebrandt, C.; Saffar, A.

2007-12-01

The island of Puerto Rico has a long history of damaging earthquakes. Major earthquakes from off-shore sources have affected Puerto Rico in 1520, 1615, 1670, 1751, 1787, 1867, and 1918 (Mueller et al, 2003; PRSN Catalogue). Recent trenching has also yielded evidence of possible M7.0 events inland (Prentice, 2000). The high seismic hazard, large population, high tsunami potential and relatively poor construction practice can result in a potentially devastating combination. Efficient emergency response in event of a large earthquake will be crucial to minimizing the loss of life and disruption of lifeline systems in Puerto Rico. The ShakeMap system (Wald et al, 2004) developed by the USGS to rapidly display and disseminate information about the geographical distribution of ground shaking (and hence potential damage) following a large earthquake has proven to be a vital tool for post earthquake emergency response efforts, and is being adopted/emulated in various seismically active regions worldwide. Implementing a robust ShakeMap system is among the top priorities of the Puerto Rico Seismic Network. However, the ultimate effectiveness of ShakeMap in post- earthquake response depends not only on its rapid availability, but also on the effective use of the information it provides. We developed ShakeMap scenarios of a suite of damaging historical and probable earthquakes that severely impact San Juan, Ponce, and Mayagüez, the 3 largest cities in Puerto Rico. Earthquake source parameters were obtained from McCann and Mercado (1998); and Huérfano (2004). For historical earthquakes that generated tsunamis, tsunami inundation maps were generated using the TIME method (Shuto, 1991). The ShakeMap ground shaking maps were presented to local and regional governmental and emergency response agencies at the 2007 Annual conference of the Puerto Rico Emergency Management and Disaster Administration in San Juan, PR, and at numerous other emergency management talks and training sessions. Economic losses are estimated using the ShakeMap scenario ground motions (Saffar, 2007). The calibration tasks necessary in generating these scenarios (developing Vs30 maps, attenuation relationships) complement the on-going efforts of the Puerto Rico Seismic Network to generate ShakeMaps in real-time.

Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans.

PubMed

Jung, Kwang-Woo; Yang, Dong-Hoon; Kim, Min-Kyu; Seo, Ho Seong; Lim, Sangyong; Bahn, Yong-Sun

2016-11-29

The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans IMPORTANCE: Although there are no natural environments under intense radiation, some living organisms have been found to show high radiation resistance. Organisms harboring the ability of radiation resistance have unique regulatory networks to overcome this stress. Cryptococcus neoformans is one of the radiation-resistant fungi and is found in highly radioactive environments. However, it remains elusive how radiation-resistant eukaryotic microorganisms work differentially from radiation-sensitive ones. Here, we performed transcriptome analysis of C. neoformans to explore gene expression profiles after gamma radiation exposure and functionally characterized some of identified radiation resistance genes. Notably, we identified a novel regulator of radiation resistance, named Bdr1 (a bZIP TF for DNA damage response 1), which is a transcription factor (TF) that is not closely homologous to any known TF and is transcriptionally controlled by the Rad53 kinase. Therefore, our work could shed light on understanding not only the radiation response but also the radiation resistance mechanism of C. neoformans. Copyright © 2016 Jung et al.

Rapid assessment of disaster damage using social media activity

PubMed Central

Kryvasheyeu, Yury; Chen, Haohui; Obradovich, Nick; Moro, Esteban; Van Hentenryck, Pascal; Fowler, James; Cebrian, Manuel

2016-01-01

Could social media data aid in disaster response and damage assessment? Countries face both an increasing frequency and an increasing intensity of natural disasters resulting from climate change. During such events, citizens turn to social media platforms for disaster-related communication and information. Social media improves situational awareness, facilitates dissemination of emergency information, enables early warning systems, and helps coordinate relief efforts. In addition, the spatiotemporal distribution of disaster-related messages helps with the real-time monitoring and assessment of the disaster itself. We present a multiscale analysis of Twitter activity before, during, and after Hurricane Sandy. We examine the online response of 50 metropolitan areas of the United States and find a strong relationship between proximity to Sandy’s path and hurricane-related social media activity. We show that real and perceived threats, together with physical disaster effects, are directly observable through the intensity and composition of Twitter’s message stream. We demonstrate that per-capita Twitter activity strongly correlates with the per-capita economic damage inflicted by the hurricane. We verify our findings for a wide range of disasters and suggest that massive online social networks can be used for rapid assessment of damage caused by a large-scale disaster. PMID:27034978

Combined loss of three DNA damage response pathways renders C. elegans intolerant to light.

PubMed

van Bostelen, Ivo; Tijsterman, Marcel

2017-06-01

Infliction of DNA damage initiates a complex cellular reaction - the DNA damage response - that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not. Yet, we observe an unprecedented synergistic relationship when these pathways are inactivated in combination. C. elegans mutants that lack nucleotide excision repair (NER), translesion synthesis (TLS) and alternative end joining (altEJ) grow undisturbed in the dark, but become sterile when grown in light. Even exposure to very low levels of normal daylight impedes animal growth. We show that NER and TLS operate to suppress the formation of lethal DNA breaks that require polymerase theta-mediated end joining (TMEJ) for their repair. Our data testifies to the enormous genotoxicity of light and to the demand of multiple layers of protection against an environmental threat that is so common. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid assessment of disaster damage using social media activity.

PubMed

Kryvasheyeu, Yury; Chen, Haohui; Obradovich, Nick; Moro, Esteban; Van Hentenryck, Pascal; Fowler, James; Cebrian, Manuel

2016-03-01

Could social media data aid in disaster response and damage assessment? Countries face both an increasing frequency and an increasing intensity of natural disasters resulting from climate change. During such events, citizens turn to social media platforms for disaster-related communication and information. Social media improves situational awareness, facilitates dissemination of emergency information, enables early warning systems, and helps coordinate relief efforts. In addition, the spatiotemporal distribution of disaster-related messages helps with the real-time monitoring and assessment of the disaster itself. We present a multiscale analysis of Twitter activity before, during, and after Hurricane Sandy. We examine the online response of 50 metropolitan areas of the United States and find a strong relationship between proximity to Sandy's path and hurricane-related social media activity. We show that real and perceived threats, together with physical disaster effects, are directly observable through the intensity and composition of Twitter's message stream. We demonstrate that per-capita Twitter activity strongly correlates with the per-capita economic damage inflicted by the hurricane. We verify our findings for a wide range of disasters and suggest that massive online social networks can be used for rapid assessment of damage caused by a large-scale disaster.

Physical and in silico approaches identify DNA-PK in a Tax DNA-damage response interactome

PubMed Central

Ramadan, Emad; Ward, Michael; Guo, Xin; Durkin, Sarah S; Sawyer, Adam; Vilela, Marcelo; Osgood, Christopher; Pothen, Alex; Semmes, Oliver J

2008-01-01

Background We have initiated an effort to exhaustively map interactions between HTLV-1 Tax and host cellular proteins. The resulting Tax interactome will have significant utility toward defining new and understanding known activities of this important viral protein. In addition, the completion of a full Tax interactome will also help shed light upon the functional consequences of these myriad Tax activities. The physical mapping process involved the affinity isolation of Tax complexes followed by sequence identification using tandem mass spectrometry. To date we have mapped 250 cellular components within this interactome. Here we present our approach to prioritizing these interactions via an in silico culling process. Results We first constructed an in silico Tax interactome comprised of 46 literature-confirmed protein-protein interactions. This number was then reduced to four Tax-interactions suspected to play a role in DNA damage response (Rad51, TOP1, Chk2, 53BP1). The first-neighbor and second-neighbor interactions of these four proteins were assembled from available human protein interaction databases. Through an analysis of betweenness and closeness centrality measures, and numbers of interactions, we ranked proteins in the first neighborhood. When this rank list was compared to the list of physical Tax-binding proteins, DNA-PK was the highest ranked protein common to both lists. An overlapping clustering of the Tax-specific second-neighborhood protein network showed DNA-PK to be one of three bridge proteins that link multiple clusters in the DNA damage response network. Conclusion The interaction of Tax with DNA-PK represents an important biological paradigm as suggested via consensus findings in vivo and in silico. We present this methodology as an approach to discovery and as a means of validating components of a consensus Tax interactome. PMID:18922151

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

PubMed Central

Rubio, Noemi; Coupienne, Isabelle; Di Valentin, Emmanuel; Heirman, Ingeborg; Grooten, Johan; Piette, Jacques; Agostinis, Patrizia

2012-01-01

Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H2O2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis. PMID:22889744

Experimental study of thin film sensor networks for wind turbine blade damage detection

NASA Astrophysics Data System (ADS)

Downey, A.; Laflamme, S.; Ubertini, F.; Sauder, H.; Sarkar, P.

2017-02-01

Damage detection of wind turbine blades is difficult due to their complex geometry and large size, for which large deployment of sensing systems is typically not economical. A solution is to develop and deploy dedicated sensor networks fabricated from inexpensive materials and electronics. The authors have recently developed a novel skin-type strain gauge for measuring strain over very large surfaces. The skin, a type of large-area electronics, is constituted from a network of soft elastomeric capacitors. The sensing system is analogous to a biological skin, where local strain can be monitored over a global area. In this paper, we propose the utilization of a dense network of soft elastomeric capacitors to detect, localize, and quantify damage on wind turbine blades. We also leverage mature off-the-shelf technologies, in particular resistive strain gauges, to augment such dense sensor network with high accuracy data at key locations, therefore constituting a hybrid dense sensor network. The proposed hybrid dense sensor network is installed inside a wind turbine blade model, and tested in a wind tunnel to simulate an operational environment. Results demonstrate the ability of the hybrid dense sensor network to detect, localize, and quantify damage.

Complex networks under dynamic repair model

NASA Astrophysics Data System (ADS)

Chaoqi, Fu; Ying, Wang; Kun, Zhao; Yangjun, Gao

2018-01-01

Invulnerability is not the only factor of importance when considering complex networks' security. It is also critical to have an effective and reasonable repair strategy. Existing research on network repair is confined to the static model. The dynamic model makes better use of the redundant capacity of repaired nodes and repairs the damaged network more efficiently than the static model; however, the dynamic repair model is complex and polytropic. In this paper, we construct a dynamic repair model and systematically describe the energy-transfer relationships between nodes in the repair process of the failure network. Nodes are divided into three types, corresponding to three structures. We find that the strong coupling structure is responsible for secondary failure of the repaired nodes and propose an algorithm that can select the most suitable targets (nodes or links) to repair the failure network with minimal cost. Two types of repair strategies are identified, with different effects under the two energy-transfer rules. The research results enable a more flexible approach to network repair.

Defoliation of interior Douglas-fir elicits carbon transfer and stress signalling to ponderosa pine neighbors through ectomycorrhizal networks.

PubMed

Song, Yuan Yuan; Simard, Suzanne W; Carroll, Allan; Mohn, William W; Zeng, Ren Sen

2015-02-16

Extensive regions of interior Douglas-fir (Pseudotsuga menziesii var. glauca, IDF) forests in North America are being damaged by drought and western spruce budworm (Choristoneura occidentalis). This damage is resulting from warmer and drier summers associated with climate change. To test whether defoliated IDF can directly transfer resources to ponderosa pine (Pinus ponderosae) regenerating nearby, thus aiding in forest recovery, we examined photosynthetic carbon transfer and defense enzyme response. We grew pairs of ectomycorrhizal IDF 'donor' and ponderosa pine 'receiver' seedlings in pots and isolated transfer pathways by comparing 35 μm, 0.5 μm and no mesh treatments; we then stressed IDF donors either through manual defoliation or infestation by the budworm. We found that manual defoliation of IDF donors led to transfer of photosynthetic carbon to neighboring receivers through mycorrhizal networks, but not through soil or root pathways. Both manual and insect defoliation of donors led to increased activity of peroxidase, polyphenol oxidase and superoxide dismutase in the ponderosa pine receivers, via a mechanism primarily dependent on the mycorrhizal network. These findings indicate that IDF can transfer resources and stress signals to interspecific neighbors, suggesting ectomycorrhizal networks can serve as agents of interspecific communication facilitating recovery and succession of forests after disturbance.

Defoliation of interior Douglas-fir elicits carbon transfer and stress signalling to ponderosa pine neighbors through ectomycorrhizal networks

PubMed Central

Song, Yuan Yuan; Simard, Suzanne W.; Carroll, Allan; Mohn, William W.; Zeng, Ren Sen

2015-01-01

Extensive regions of interior Douglas-fir (Pseudotsuga menziesii var. glauca, IDF) forests in North America are being damaged by drought and western spruce budworm (Choristoneura occidentalis). This damage is resulting from warmer and drier summers associated with climate change. To test whether defoliated IDF can directly transfer resources to ponderosa pine (Pinus ponderosae) regenerating nearby, thus aiding in forest recovery, we examined photosynthetic carbon transfer and defense enzyme response. We grew pairs of ectomycorrhizal IDF ‘donor’ and ponderosa pine ‘receiver’ seedlings in pots and isolated transfer pathways by comparing 35 μm, 0.5 μm and no mesh treatments; we then stressed IDF donors either through manual defoliation or infestation by the budworm. We found that manual defoliation of IDF donors led to transfer of photosynthetic carbon to neighboring receivers through mycorrhizal networks, but not through soil or root pathways. Both manual and insect defoliation of donors led to increased activity of peroxidase, polyphenol oxidase and superoxide dismutase in the ponderosa pine receivers, via a mechanism primarily dependent on the mycorrhizal network. These findings indicate that IDF can transfer resources and stress signals to interspecific neighbors, suggesting ectomycorrhizal networks can serve as agents of interspecific communication facilitating recovery and succession of forests after disturbance. PMID:25683155

Modulation of DNA damage response and induction of apoptosis mediates synergism between doxorubicin and a new imidazopyridine derivative in breast and lung cancer cells.

PubMed

El-Awady, Raafat A; Semreen, Mohammad H; Saber-Ayad, Maha M; Cyprian, Farhan; Menon, Varsha; Al-Tel, Taleb H

2016-01-01

DNA damage response machinery (DDR) is an attractive target of cancer therapy. Modulation of DDR network may alter the response of cancer cells to DNA damaging anticancer drugs such as doxorubicin. The aim of the present study is to investigate the effects of a newly developed imidazopyridine (IAZP) derivative on the DDR after induction of DNA damage in cancer cells by doxorubicin. Cytotoxicity sulphrhodamine-B assay showed a weak anti-proliferative effect of IAZP alone on six cancer cell lines (MCF7, A549, A549DOX11, HepG2, HeLa and M8) and a normal fibroblast strain. Combination of IAZP with doxorubicin resulted in synergism in lung (A549) and breast (MCF7) cancer cells but neither in the other cancer cell lines nor in normal fibroblasts. Molecular studies revealed that synergism is mediated by modulation of DNA damage response and induction of apoptosis. Using constant-field gel electrophoresis and immunofluorescence detection of γ-H2AX foci, IAZP was shown to inhibit the repair of doxorubicin-induced DNA damage in A549 and MCF7 cells. Immunoblot analysis showed that IAZP suppresses the phosphorylation of the ataxia lelangiectasia and Rad3 related (ATR) protein, which is an important player in the response of cancer cells to chemotherapy-induced DNA damage. Moreover, IAZP augmented the doxorubicin-induced degradation of p21, activation of p53, CDK2, caspase 3/7 and phosphorylation of Rb protein. These effects enhanced doxorubicin-induced apoptosis in both cell lines. Our results indicate that IAZP is a promising agent that may enhance the cytotoxic effects of doxorubicin on some cancer cells through targeting the DDR. It is a preliminary step toward the clinical application of IAZP in combination with anticancer drugs and opens the avenue for the development of compounds targeting the DDR pathway that might improve the therapeutic index of anticancer drugs and enhance their cure rate. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrating plant and animal biology for the search of novel DNA damage biomarkers.

PubMed

Nikitaki, Zacharenia; Holá, Marcela; Donà, Mattia; Pavlopoulou, Athanasia; Michalopoulos, Ioannis; Angelis, Karel J; Georgakilas, Alexandros G; Macovei, Anca; Balestrazzi, Alma

Eukaryotic genome surveillance is dependent on the multiple, highly coordinated network functions of the DNA damage response (DDR). Highlighted conserved features of DDR in plants and animals represent a challenging opportunity to develop novel interdisciplinary investigations aimed at expanding the sets of DNA damage biomarkers currently available for radiation exposure monitoring (REM) in environmental and biomedical applications. In this review, common and divergent features of the most relevant DDR players in animals and plants are described, including the intriguing example of the plant and animal kingdom-specific master regulators SOG1 (suppressor of gamma response) and p53. The potential of chromatin remodelers as novel predictive biomarkers of DNA damage is considered since these highly evolutionarily conserved proteins provide a docking platform for the DNA repair machinery. The constraints of conventional REM biomarkers can be overcome using biomarkers identified with the help of the pool provided by high-throughput techniques. The complexity of radiation-responsive animal and plant transcriptomes and their usefulness as sources of novel REM biomarkers are discussed, focusing on ionizing (IR) and UV-radiation. The possible advantages resulting from the exploitation of plants as sources of novel DNA damage biomarkers for monitoring the response to radiation-mediated genotoxic stress are listed. Plants could represent an ideal system for the functional characterization of knockout mutations in DDR genes which compromise cell survival in animals. However, the pronounced differences between plant and animal cells need to be carefully considered in order to avoid any misleading interpretations. Radioresistant plant-based systems might be useful to explore the molecular bases of LD (low dose)/LDR (low dose rate) responses since nowadays it is extremely difficult to perform an accurate assessment of LD/LDR risk to human health. To overcome these constraints, researchers have started exploring radiotolerant non-human species as potential sources of information on the mechanisms involved in LD/LDR and general radiation responses. Copyright © 2018 Elsevier B.V. All rights reserved.

Cytokines in Sepsis: Potent Immunoregulators and Potential Therapeutic Targets—An Updated View

PubMed Central

Bernhagen, Jürgen; Bucala, Richard

2013-01-01

Sepsis and septic shock are among the leading causes of death in intensive care units worldwide. Numerous studies on their pathophysiology have revealed an imbalance in the inflammatory network leading to tissue damage, organ failure, and ultimately, death. Cytokines are important pleiotropic regulators of the immune response, which have a crucial role in the complex pathophysiology underlying sepsis. They have both pro- and anti-inflammatory functions and are capable of coordinating effective defense mechanisms against invading pathogens. On the other hand, cytokines may dysregulate the immune response and promote tissue-damaging inflammation. In this review, we address the current knowledge of the actions of pro- and anti-inflammatory cytokines in sepsis pathophysiology as well as how these cytokines and other important immunomodulating agents may be therapeutically targeted to improve the clinical outcome of sepsis. PMID:23853427

Sample EP Flow Analysis of Severely Damaged Networks

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

Werley, Kenneth Alan; McCown, Andrew William

These are slides for a presentation at the working group meeting of the WESC SREMP Software Product Integration Team on sample EP flow analysis of severely damaged networks. The following topics are covered: ERCOT EP Transmission Model; Zoomed in to Houston and Overlaying StreetAtlas; EMPACT Solve/Dispatch/Shedding Options; QACS BaseCase Power Flow Solution; 3 Substation Contingency; Gen. & Load/100 Optimal Dispatch; Dispatch Results; Shed Load for Low V; Network Damage Summary; Estimated Service Areas (Potential); Estimated Outage Areas (potential).

Fanconi anemia: a disorder defective in the DNA damage response.

PubMed

Kitao, Hiroyuki; Takata, Minoru

2011-04-01

Fanconi anemia (FA) is a cancer predisposition disorder characterized by progressive bone marrow failure, congenital developmental defects, chromosomal abnormalities, and cellular hypersensitivity to DNA interstrand crosslink (ICL) agents. So far mutations in 14 FANC genes were identified in FA or FA-like patients. These gene products constitute a common ubiquitin-phosphorylation network called the "FA pathway" and cooperate with other proteins involved in DNA repair and cell cycle control to repair ICL lesions and to maintain genome stability. In this review, we summarize recent exciting discoveries that have expanded our view of the molecular mechanisms operating in DNA repair and DNA damage signaling.

Criticality in finite dynamical networks

NASA Astrophysics Data System (ADS)

Rohlf, Thimo; Gulbahce, Natali; Teuscher, Christof

2007-03-01

It has been shown analytically and experimentally that both random boolean and random threshold networks show a transition from ordered to chaotic dynamics at a critical average connectivity Kc in the thermodynamical limit [1]. By looking at the statistical distributions of damage spreading (damage sizes), we go beyond this extensively studied mean-field approximation. We study the scaling properties of damage size distributions as a function of system size N and initial perturbation size d(t=0). We present numerical evidence that another characteristic point, Kd exists for finite system sizes, where the expectation value of damage spreading in the network is independent of the system size N. Further, the probability to obtain critical networks is investigated for a given system size and average connectivity k. Our results suggest that, for finite size dynamical networks, phase space structure is very complex and may not exhibit a sharp order-disorder transition. Finally, we discuss the implications of our findings for evolutionary processes and learning applied to networks which solve specific computational tasks. [1] Derrida, B. and Pomeau, Y. (1986), Europhys. Lett., 1, 45-49

Site Effects in the City of Port au Prince (Haiti) Inferred From 2010 Earthquake Aftershocks Recordings.

NASA Astrophysics Data System (ADS)

ST Fleur, S.; Courboulex, F.; Bertrand, E.; Deschamps, A.; Mercier De Lepinay, B. F.; Boisson, D.; Prepetit, C.; Hough, S. E.

2014-12-01

The Haitian earthquake of 12 January 2010 (Mw=7) caused an unprecedented disaster in Port-au-Prince as well as in smaller cities close to the epicenter. The extent of damage appears to be initially attributed to the proximity of the earthquake in Port-au-Prince, the extreme vulnerability of many structures, and a high population density. However, the damage distribution for this earthquake suggests a general correlation of damage with small-scale topographical features and local geological structure. The main objective of this work is to investigate site effects in the city of Port-au-Prince. It is also to better define the response of different sites to earthquakes and establish transfer functions between each site and a particular site defined as a reference site. Specific soil columns is determined in the vicinity of each station in order to carry out 1D simulations of soil response at these sites. About 90 earthquakes (2

Flat Surface Damage Detection System (FSDDS)

NASA Technical Reports Server (NTRS)

Williams, Martha; Lewis, Mark; Gibson, Tracy; Lane, John; Medelius, Pedro; Snyder, Sarah; Ciarlariello, Dan; Parks, Steve; Carrejo, Danny; Rojdev, Kristina

2013-01-01

The Flat Surface Damage Detection system (FSDDS} is a sensory system that is capable of detecting impact damages to surfaces utilizing a novel sensor system. This system will provide the ability to monitor the integrity of an inflatable habitat during in situ system health monitoring. The system consists of three main custom designed subsystems: the multi-layer sensing panel, the embedded monitoring system, and the graphical user interface (GUI). The GUI LABVIEW software uses a custom developed damage detection algorithm to determine the damage location based on the sequence of broken sensing lines. It estimates the damage size, the maximum depth, and plots the damage location on a graph. Successfully demonstrated as a stand alone technology during 2011 D-RATS. Software modification also allowed for communication with HDU avionics crew display which was demonstrated remotely (KSC to JSC} during 2012 integration testing. Integrated FSDDS system and stand alone multi-panel systems were demonstrated remotely and at JSC, Mission Operations Test using Space Network Research Federation (SNRF} network in 2012. FY13, FSDDS multi-panel integration with JSC and SNRF network Technology can allow for integration with other complementary damage detection systems.

Istanbul Earthquake Early Warning and Rapid Response System

NASA Astrophysics Data System (ADS)

Erdik, M. O.; Fahjan, Y.; Ozel, O.; Alcik, H.; Aydin, M.; Gul, M.

2003-12-01

As part of the preparations for the future earthquake in Istanbul a Rapid Response and Early Warning system in the metropolitan area is in operation. For the Early Warning system ten strong motion stations were installed as close as possible to the fault zone. Continuous on-line data from these stations via digital radio modem provide early warning for potentially disastrous earthquakes. Considering the complexity of fault rupture and the short fault distances involved, a simple and robust Early Warning algorithm, based on the exceedance of specified threshold time domain amplitude levels is implemented. The band-pass filtered accelerations and the cumulative absolute velocity (CAV) are compared with specified threshold levels. When any acceleration or CAV (on any channel) in a given station exceeds specific threshold values it is considered a vote. Whenever we have 2 station votes within selectable time interval, after the first vote, the first alarm is declared. In order to specify the appropriate threshold levels a data set of near field strong ground motions records form Turkey and the world has been analyzed. Correlations among these thresholds in terms of the epicenter distance the magnitude of the earthquake have been studied. The encrypted early warning signals will be communicated to the respective end users by UHF systems through a "service provider" company. The users of the early warning signal will be power and gas companies, nuclear research facilities, critical chemical factories, subway system and several high-rise buildings. Depending on the location of the earthquake (initiation of fault rupture) and the recipient facility the alarm time can be as high as about 8s. For the rapid response system one hundred 18 bit-resolution strong motion accelerometers were placed in quasi-free field locations (basement of small buildings) in the populated areas of the city, within an area of approximately 50x30km, to constitute a network that will enable early damage assessment and rapid response information after a damaging earthquake. Early response information is achieved through fast acquisition and analysis of processed data obtained from the network. The stations are routinely interrogated on regular basis by the main data center. After triggered by an earthquake, each station processes the streaming strong motion data to yield the spectral accelerations at specific periods, 12Hz filtered PGA and PGV and will send these parameters in the form of SMS messages at every 20s directly to the main data center through a designated GSM network and through a microwave system. A shake map and damage distribution map (using aggregate building inventories and fragility curves) will be automatically generated using the algorithm developed for this purpose. Loss assessment studies are complemented by a large citywide digital database on the topography, geology, soil conditions, building, infrastructure and lifeline inventory. The shake and damage maps will be conveyed to the governor's and mayor's offices, fire, police and army headquarters within 3 minutes using radio modem and GPRS communication. An additional forty strong motion recorders were placed on important structures in several interconnected clusters to monitor the health of these structures after a damaging earthquake.

Nedd4 Family Interacting Protein 1 (Ndfip1) Is Required for Ubiquitination and Nuclear Trafficking of BRCA1-associated ATM Activator 1 (BRAT1) during the DNA Damage Response*

PubMed Central

Low, Ley-Hian; Chow, Yuh-Lit; Li, Yijia; Goh, Choo-Peng; Putz, Ulrich; Silke, John; Ouchi, Toru; Howitt, Jason; Tan, Seong-Seng

2015-01-01

During injury, cells are vulnerable to apoptosis from a variety of stress conditions including DNA damage causing double-stranded breaks. Without repair, these breaks lead to aberrations in DNA replication and transcription, leading to apoptosis. A major response to DNA damage is provided by the protein kinase ATM (ataxia telangiectasia mutated) that is capable of commanding a plethora of signaling networks for DNA repair, cell cycle arrest, and even apoptosis. A key element in the DNA damage response is the mobilization of activating proteins into the cell nucleus to repair damaged DNA. BRAT1 is one of these proteins, and it functions as an activator of ATM by maintaining its phosphorylated status while also keeping other phosphatases at bay. However, it is unknown how BRAT1 is trafficked into the cell nucleus to maintain ATM phosphorylation. Here we demonstrate that Ndfip1-mediated ubiquitination of BRAT1 leads to BRAT1 trafficking into the cell nucleus. Without Ndfip1, BRAT1 failed to translocate to the nucleus. Under genotoxic stress, cells showed increased expression of both Ndfip1 and phosphorylated ATM. Following brain injury, neurons show increased expression of Ndfip1 and nuclear translocation of BRAT1. These results point to Ndfip1 as a sensor protein during cell injury and Ndfip1 up-regulation as a cue for BRAT1 ubiquitination by Nedd4 E3 ligases, followed by nuclear translocation of BRAT1. PMID:25631046

Autonomous smart sensor network for full-scale structural health monitoring

NASA Astrophysics Data System (ADS)

Rice, Jennifer A.; Mechitov, Kirill A.; Spencer, B. F., Jr.; Agha, Gul A.

2010-04-01

The demands of aging infrastructure require effective methods for structural monitoring and maintenance. Wireless smart sensor networks offer the ability to enhance structural health monitoring (SHM) practices through the utilization of onboard computation to achieve distributed data management. Such an approach is scalable to the large number of sensor nodes required for high-fidelity modal analysis and damage detection. While smart sensor technology is not new, the number of full-scale SHM applications has been limited. This slow progress is due, in part, to the complex network management issues that arise when moving from a laboratory setting to a full-scale monitoring implementation. This paper presents flexible network management software that enables continuous and autonomous operation of wireless smart sensor networks for full-scale SHM applications. The software components combine sleep/wake cycling for enhanced power management with threshold detection for triggering network wide tasks, such as synchronized sensing or decentralized modal analysis, during periods of critical structural response.

Mapping the Structure of Directed Networks: Beyond the Bow-Tie Diagram

NASA Astrophysics Data System (ADS)

Timár, G.; Goltsev, A. V.; Dorogovtsev, S. N.; Mendes, J. F. F.

2017-02-01

We reveal a hierarchical, multilayer organization of finite components—i.e., tendrils and tubes—around the giant connected components in directed networks and propose efficient algorithms allowing one to uncover the entire organization of key real-world directed networks, such as the World Wide Web, the neural network of Caenorhabditis elegans, and others. With increasing damage, the giant components decrease in size while the number and size of tendril layers increase, enhancing the susceptibility of the networks to damage.

On damage diagnosis for a wind turbine blade using pattern recognition

NASA Astrophysics Data System (ADS)

Dervilis, N.; Choi, M.; Taylor, S. G.; Barthorpe, R. J.; Park, G.; Farrar, C. R.; Worden, K.

2014-03-01

With the increased interest in implementation of wind turbine power plants in remote areas, structural health monitoring (SHM) will be one of the key cards in the efficient establishment of wind turbines in the energy arena. Detection of blade damage at an early stage is a critical problem, as blade failure can lead to a catastrophic outcome for the entire wind turbine system. Experimental measurements from vibration analysis were extracted from a 9 m CX-100 blade by researchers at Los Alamos National Laboratory (LANL) throughout a full-scale fatigue test conducted at the National Renewable Energy Laboratory (NREL) and National Wind Technology Center (NWTC). The blade was harmonically excited at its first natural frequency using a Universal Resonant EXcitation (UREX) system. In the current study, machine learning algorithms based on Artificial Neural Networks (ANNs), including an Auto-Associative Neural Network (AANN) based on a standard ANN form and a novel approach to auto-association with Radial Basis Functions (RBFs) networks are used, which are optimised for fast and efficient runs. This paper introduces such pattern recognition methods into the wind energy field and attempts to address the effectiveness of such methods by combining vibration response data with novelty detection techniques.

p18(Hamlet) mediates different p53-dependent responses to DNA-damage inducing agents.

PubMed

Lafarga, Vanesa; Cuadrado, Ana; Nebreda, Angel R

2007-10-01

Cells organize appropriate responses to environmental cues by activating specific signaling networks. Two proteins that play key roles in coordinating stress responses are the kinase p38alpha (MAPK14) and the transcription factor p53 (TP53). Depending on the nature and the extent of the stress-induced damage, cells may respond by arresting the cell cycle or by undergoing cell death, and these responses are usually associated with the phosphorylation of particular substrates by p38alpha as well as the activation of specific target genes by p53. We recently characterized a new p38alpha substrate, named p18(Hamlet) (ZNHIT1), which mediates p53-dependent responses to different genotoxic stresses. Thus, cisplatin or UV light induce stabilization of the p18(Hamlet) protein, which then enhances the ability of p53 to bind to and activate the promoters of pro-apoptotic genes such as NOXA and PUMA leading to apoptosis induction. In a similar way, we report here that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A).

RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response

PubMed Central

Maréchal, Alexandre; Zou, Lee

2015-01-01

The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications. PMID:25403473

RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response.

PubMed

Maréchal, Alexandre; Zou, Lee

2015-01-01

The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications.

Flight Test of an Adaptive Controller and Simulated Failure/Damage on the NASA NF-15B

NASA Technical Reports Server (NTRS)

Buschbacher, Mark; Maliska, Heather

2006-01-01

The method of flight-testing the Intelligent Flight Control System (IFCS) Second Generation (Gen-2) project on the NASA NF-15B is herein described. The Gen-2 project objective includes flight-testing a dynamic inversion controller augmented by a direct adaptive neural network to demonstrate performance improvements in the presence of simulated failure/damage. The Gen-2 objectives as implemented on the NASA NF-15B created challenges for software design, structural loading limitations, and flight test operations. Simulated failure/damage is introduced by modifying control surface commands, therefore requiring structural loads measurements. Flight-testing began with the validation of a structural loads model. Flight-testing of the Gen-2 controller continued, using test maneuvers designed in a sequenced approach. Success would clear the new controller with respect to dynamic response, simulated failure/damage, and with adaptation on and off. A handling qualities evaluation was conducted on the capability of the Gen-2 controller to restore aircraft response in the presence of a simulated failure/damage. Control room monitoring of loads sensors, flight dynamics, and controller adaptation, in addition to postflight data comparison to the simulation, ensured a safe methodology of buildup testing. Flight-testing continued without major incident to accomplish the project objectives, successfully uncovering strengths and weaknesses of the Gen-2 control approach in flight.

Leptospira interrogans serovar copenhageni harbors two lexA genes involved in SOS response.

PubMed

Fonseca, Luciane S; da Silva, Josefa B; Milanez, Juliana S; Monteiro-Vitorello, Claudia B; Momo, Leonardo; de Morais, Zenaide M; Vasconcellos, Silvio A; Marques, Marilis V; Ho, Paulo L; da Costa, Renata M A

2013-01-01

Bacteria activate a regulatory network in response to the challenges imposed by DNA damage to genetic material, known as the SOS response. This system is regulated by the RecA recombinase and by the transcriptional repressor lexA. Leptospira interrogans is a pathogen capable of surviving in the environment for weeks, being exposed to a great variety of stress agents and yet retaining its ability to infect the host. This study aims to investigate the behavior of L. interrogans serovar Copenhageni after the stress induced by DNA damage. We show that L. interrogans serovar Copenhageni genome contains two genes encoding putative LexA proteins (lexA1 and lexA2) one of them being potentially acquired by lateral gene transfer. Both genes are induced after DNA damage, but the steady state levels of both LexA proteins drop, probably due to auto-proteolytic activity triggered in this condition. In addition, seven other genes were up-regulated following UV-C irradiation, recA, recN, dinP, and four genes encoding hypothetical proteins. This set of genes is potentially regulated by LexA1, as it showed binding to their promoter regions. All these regions contain degenerated sequences in relation to the previously described SOS box, TTTGN 5CAAA. On the other hand, LexA2 was able to bind to the palindrome TTGTAN10TACAA, found in its own promoter region, but not in the others. Therefore, the L. interrogans serovar Copenhageni SOS regulon may be even more complex, as a result of LexA1 and LexA2 binding to divergent motifs. New possibilities for DNA damage response in Leptospira are expected, with potential influence in other biological responses such as virulence.

Leptospira interrogans serovar Copenhageni Harbors Two lexA Genes Involved in SOS Response

PubMed Central

Fonseca, Luciane S.; da Silva, Josefa B.; Milanez, Juliana S.; Monteiro-Vitorello, Claudia B.; Momo, Leonardo; de Morais, Zenaide M.; Vasconcellos, Silvio A.; Marques, Marilis V.; Ho, Paulo L.; da Costa, Renata M. A.

2013-01-01

Bacteria activate a regulatory network in response to the challenges imposed by DNA damage to genetic material, known as the SOS response. This system is regulated by the RecA recombinase and by the transcriptional repressor lexA. Leptospira interrogans is a pathogen capable of surviving in the environment for weeks, being exposed to a great variety of stress agents and yet retaining its ability to infect the host. This study aims to investigate the behavior of L. interrogans serovar Copenhageni after the stress induced by DNA damage. We show that L. interrogans serovar Copenhageni genome contains two genes encoding putative LexA proteins (lexA1 and lexA2) one of them being potentially acquired by lateral gene transfer. Both genes are induced after DNA damage, but the steady state levels of both LexA proteins drop, probably due to auto-proteolytic activity triggered in this condition. In addition, seven other genes were up-regulated following UV-C irradiation, recA, recN, dinP, and four genes encoding hypothetical proteins. This set of genes is potentially regulated by LexA1, as it showed binding to their promoter regions. All these regions contain degenerated sequences in relation to the previously described SOS box, TTTGN 5CAAA. On the other hand, LexA2 was able to bind to the palindrome TTGTAN 10TACAA, found in its own promoter region, but not in the others. Therefore, the L. interrogans serovar Copenhageni SOS regulon may be even more complex, as a result of LexA1 and LexA2 binding to divergent motifs. New possibilities for DNA damage response in Leptospira are expected, with potential influence in other biological responses such as virulence. PMID:24098496

Chromatin relaxation-mediated induction of p19INK4d increases the ability of cells to repair damaged DNA.

PubMed

Ogara, María F; Sirkin, Pablo F; Carcagno, Abel L; Marazita, Mariela C; Sonzogni, Silvina V; Ceruti, Julieta M; Cánepa, Eduardo T

2013-01-01

The maintenance of genomic integrity is of main importance to the survival and health of organisms which are continuously exposed to genotoxic stress. Cells respond to DNA damage by activating survival pathways consisting of cell cycle checkpoints and repair mechanisms. However, the signal that triggers the DNA damage response is not necessarily a direct detection of the primary DNA lesion. In fact, chromatin defects may serve as initiating signals to activate those mechanisms. If the modulation of chromatin structure could initiate a checkpoint response in a direct manner, this supposes the existence of specific chromatin sensors. p19INK4d, a member of the INK4 cell cycle inhibitors, plays a crucial role in regulating genomic stability and cell viability by enhancing DNA repair. Its expression is induced in cells injured by one of several genotoxic treatments like cis-platin, UV light or neocarzinostatin. Nevertheless, when exogenous DNA damaged molecules are introduced into the cell, this induction is not observed. Here, we show that p19INK4d is enhanced after chromatin relaxation even in the absence of DNA damage. This induction was shown to depend upon ATM/ATR, Chk1/Chk2 and E2F activity, as is the case of p19INK4d induction by endogenous DNA damage. Interestingly, p19INK4d improves DNA repair when the genotoxic damage is caused in a relaxed-chromatin context. These results suggest that changes in chromatin structure, and not DNA damage itself, is the actual trigger of p19INK4d induction. We propose that, in addition to its role as a cell cycle inhibitor, p19INK4d could participate in a signaling network directed to detecting and eventually responding to chromatin anomalies.

Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes

PubMed Central

2012-01-01

Background The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Results Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Conclusions Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an essential role in these organisms and sheds light into the mechanisms of evolution of global transcriptional networks involved in adaptability and rapid response to environmental changes, suggesting that small chromosomes may act as evolutionary test beds for the rewiring of transcriptional networks. PMID:22305460

Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs

PubMed Central

Furst, Audrey; Koch, Marc; Fischer, Benoit; Soutoglou, Evi

2016-01-01

DNA lesions are sensed by a network of proteins that trigger the DNA damage response (DDR), a signaling cascade that acts to delay cell cycle progression and initiate DNA repair. The Mediator of DNA damage Checkpoint protein 1 (MDC1) is essential for spreading of the DDR signaling on chromatin surrounding Double Strand Breaks (DSBs) by acting as a scaffold for PI3K kinases and for ubiquitin ligases. MDC1 also plays a role both in Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR) repair pathways. Here we identify two novel binding partners of MDC1, the poly (ADP-ribose) Polymerases (PARPs) TNKS1 and 2. We find that TNKSs are recruited to DNA lesions by MDC1 and regulate DNA end resection and BRCA1A complex stabilization at lesions leading to efficient DSB repair by HR and proper checkpoint activation. PMID:26845027

Recovery from DNA damage-induced G2 arrest requires actin-binding protein filamin-A/actin-binding protein 280.

PubMed

Meng, Xiangbing; Yuan, Yuan; Maestas, Adrian; Shen, Zhiyuan

2004-02-13

Filamin-A (filamin-1) is an actin-binding protein involved in the organization of actin networks. Our previous study shows that filamin-A interacts with BRCA2, and lack of filamin-A expression results in increased cellular sensitivity to several DNA damaging agents in melanoma cells (Yuan, Y., and Shen, Z. (2001) J. Biol. Chem. 276, 48318-48324), suggesting a role of filamin-A in DNA damage response. In this report, we demonstrated that deficiency of filamin-A results in an 8-h delay in the recovery from G2 arrest in response to ionizing radiation. However, filamin-A deficiency does not affect the initial activation of the G2/M checkpoint. We also found that filamin-A deficiency results in sustained activation of Chk1 and Chk2 after irradiation. This in turn causes a delay in the dephosphorylation of phospho-Cdc2, which is inhibitory to the G2/M transition. In addition, filamin-A-deficient M2 cells undergo mitotic catastrophe-related nuclear fragmentation after they are released from the G2 arrest. Together, these data suggest a functional role of filamin-A in the recovery from G2 arrest and subsequent mitotic cell death after DNA damage.

Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break

PubMed Central

Lindgren, Emma; Hägg, Sara; Giordano, Fosco; Björkegren, Johan; Ström, Lena

2014-01-01

Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding. PMID:25483075

In situ sensing of non-linear deformation and damage in epoxy particulate composites

NASA Astrophysics Data System (ADS)

Vadlamani, Venkat K.; Chalivendra, Vijaya; Shukla, Arun; Yang, Sze

2012-07-01

Damage sensing of epoxy particulate composites was investigated using multi-wall carbon nanotubes (MWCNTs) under quasi-static uniaxial tensile loading. Two types of particulates, namely (a) aluminum silicate hollow microspheres (cenospheres), and (b) liquid carboxyl-terminated butadiene acrylonitrile (CTBN) rubber were considered in this study. The influence of three different volume fractions of cenospheres (10%, 20% and 30%) and three different weight fractions of CTBN resin (10, 20 and 30 phr) on the electromechanical response was studied. A four-circumferential ring probe (FCRP) technique was employed to measure the electrical resistance of the test specimen as a function of the axial strain. The resistance-strain curve is compared with a simultaneously measured mechanical stress-strain curve. The electromechanical measurement show additional stages of material deformation not readily revealed from the mechanical stress-strain curve. The resistance change associated with the unfolding of entangled polymer chains and further straightening of the polymer chains decreased the distance between CNTs, causing improved electron hopping in all composites except 30% cenospheres composite. The U-shaped electrical response demonstrated by both 20 and 30 phr rubber composites exploited the CNT sensory network successfully by providing early warning of composite failure due to micro-crack propagation which resulted in breaking of the CNT network.

The autophagy interaction network of the aging model Podospora anserina.

PubMed

Philipp, Oliver; Hamann, Andrea; Osiewacz, Heinz D; Koch, Ina

2017-03-27

Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. It is active either as response to starvation or molecular damage. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. In earlier studies, it was found that autophagy in the aging model Podospora anserina acts as a longevity assurance mechanism. However, only little is known about the individual components controlling autophagy in this aging model. Here, we report a biochemical and bioinformatics study to detect the protein-protein interaction (PPI) network of P. anserina combining experimental and theoretical methods. We constructed the PPI network of autophagy in P. anserina based on the corresponding networks of yeast and human. We integrated PaATG8 interaction partners identified in an own yeast two-hybrid analysis using ATG8 of P. anserina as bait. Additionally, we included age-dependent transcriptome data. The resulting network consists of 89 proteins involved in 186 interactions. We applied bioinformatics approaches to analyze the network topology and to prove that the network is not random, but exhibits biologically meaningful properties. We identified hub proteins which play an essential role in the network as well as seven putative sub-pathways, and interactions which are likely to be evolutionary conserved amongst species. We confirmed that autophagy-associated genes are significantly often up-regulated and co-expressed during aging of P. anserina. With the present study, we provide a comprehensive biological network of the autophagy pathway in P. anserina comprising PPI and gene expression data. It is based on computational prediction as well as experimental data. We identified sub-pathways, important hub proteins, and evolutionary conserved interactions. The network clearly illustrates the relation of autophagy to aging processes and enables further specific studies to understand autophagy and aging in P. anserina as well as in other systems.

Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition.

PubMed

Kirkpatrick, Donald S; Bustos, Daisy J; Dogan, Taner; Chan, Jocelyn; Phu, Lilian; Young, Amy; Friedman, Lori S; Belvin, Marcia; Song, Qinghua; Bakalarski, Corey E; Hoeflich, Klaus P

2013-11-26

Targeted therapeutics that block signal transduction through the RAS-RAF-MEK and PI3K-AKT-mTOR pathways offer significant promise for the treatment of human malignancies. Dual inhibition of MAP/ERK kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) with the potent and selective small-molecule inhibitors GDC-0973 and GDC-0941 has been shown to trigger tumor cell death in preclinical models. Here we have used phosphomotif antibodies and mass spectrometry (MS) to investigate the effects of MEK/PI3K dual inhibition during the period immediately preceding cell death. Upon treatment, melanoma cell lines responded by dramatically increasing phosphorylation on proteins containing a canonical DNA damage-response (DDR) motif, as defined by a phosphorylated serine or threonine residue adjacent to glutamine, [s/t]Q. In total, >2,000 [s/t]Q phosphorylation sites on >850 proteins were identified by LC-MS/MS, including an extensive network of DDR proteins. Linear mixed-effects modeling revealed 101 proteins in which [s/t]Q phosphorylation was altered significantly in response to GDC-0973/GDC-0941. Among the most dramatic changes, we observed rapid and sustained phosphorylation of sites within the ABCDE cluster of DNA-dependent protein kinase. Preincubation of cells with the inhibitors of the DDR kinases DNA-dependent protein kinase or ataxia-telangiectasia mutated enhanced GDC-0973/GDC-0941-mediated cell death. Network analysis revealed specific enrichment of proteins involved in RNA metabolism along with canonical DDR proteins and suggested a prominent role for this pathway in the response to MEK/PI3K dual inhibition.

Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition

PubMed Central

Kirkpatrick, Donald S.; Bustos, Daisy J.; Dogan, Taner; Chan, Jocelyn; Phu, Lilian; Young, Amy; Friedman, Lori S.; Belvin, Marcia; Song, Qinghua; Bakalarski, Corey E.; Hoeflich, Klaus P.

2013-01-01

Targeted therapeutics that block signal transduction through the RAS–RAF–MEK and PI3K–AKT–mTOR pathways offer significant promise for the treatment of human malignancies. Dual inhibition of MAP/ERK kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) with the potent and selective small-molecule inhibitors GDC-0973 and GDC-0941 has been shown to trigger tumor cell death in preclinical models. Here we have used phosphomotif antibodies and mass spectrometry (MS) to investigate the effects of MEK/PI3K dual inhibition during the period immediately preceding cell death. Upon treatment, melanoma cell lines responded by dramatically increasing phosphorylation on proteins containing a canonical DNA damage-response (DDR) motif, as defined by a phosphorylated serine or threonine residue adjacent to glutamine, [s/t]Q. In total, >2,000 [s/t]Q phosphorylation sites on >850 proteins were identified by LC-MS/MS, including an extensive network of DDR proteins. Linear mixed-effects modeling revealed 101 proteins in which [s/t]Q phosphorylation was altered significantly in response to GDC-0973/GDC-0941. Among the most dramatic changes, we observed rapid and sustained phosphorylation of sites within the ABCDE cluster of DNA-dependent protein kinase. Preincubation of cells with the inhibitors of the DDR kinases DNA-dependent protein kinase or ataxia-telangiectasia mutated enhanced GDC-0973/GDC-0941–mediated cell death. Network analysis revealed specific enrichment of proteins involved in RNA metabolism along with canonical DDR proteins and suggested a prominent role for this pathway in the response to MEK/PI3K dual inhibition. PMID:24218548

Monitoring Network and Interfacial Healing Processes by Broadband Dielectric Spectroscopy: A Case Study on Natural Rubber.

PubMed

Hernández, M; Grande, A M; van der Zwaag, S; García, S J

2016-04-27

Broadband dielectric spectroscopy (BDS) is introduced as a new and powerful technique to monitor network and macroscale damage healing in an elastomer. For the proof of concept, a partially cured sulfur-cured natural rubber (NR) containing reversible disulfides as the healing moiety was employed. The forms of damage healed and monitored were an invisible damage in the rubber network due to multiple straining and an imposed macroscopic crack. The relaxation times of pristine, damaged, and healed samples were determined and fitted to the Havriliak-Negami equation to obtain the characteristic polymer parameters. It is shown that seemingly full mechanical healing occurred regardless the type of damage, while BDS demonstrates that the polymer architecture in the healed material differs from that in the original one. These results represent a step forward in the understanding of damage and healing processes in intrinsic self-healing polymer systems with prospective applications such as coatings, tires, seals, and gaskets.

The role of topology in microstructure-property relations: a 2D DEM based study

NASA Astrophysics Data System (ADS)

Saleme Ruiz, Katerine; Emelianenko, Maria

2018-01-01

We compare Rényi entropy-based mesoscale approaches for characterizing 2D polycrystalline network topology and geometry, based on the grain number of sides and grain areas, respectively. We study the effect of microstructure disorder on mechanical properties such as elastic and damage response by performing simulations of quasi-static uniaxial compression loading tests on an idealized material using grain-level micro-mechanical discrete element model. While not comprehensive enough to make general conclusions, this study allows us to make observations about the sensitivity of mechanical parameters such as Young's modulus, proportional limit, first yield stress, toughness and amount of microstructure damage to different entropy measures.

Site response in the eastern United States: A comparison of Vs30 measurements with estimates from horizontal:vertical spectral ratios

USGS Publications Warehouse

McNamara, Daniel E.; Stephenson, William J.; Odum, Jackson K.; Williams, Robert; Gee, Lind

2014-01-01

Earthquake damage is often increased due to local ground-motion amplification caused by soft soils, thick basin sediments, topographic effects, and liquefaction. A critical factor contributing to the assessment of seismic hazard is detailed information on local site response. In order to address and quantify the site response at seismograph stations in the eastern United States, we investigate the regional spatial variation of horizontal:vertical spectral ratios (HVSR) using ambient noise recorded at permanent regional and national network stations as well as temporary seismic stations deployed in order to record aftershocks of the 2011 Mineral, Virginia, earthquake. We compare the HVSR peak frequency to surface measurements of the shear-wave seismic velocity to 30 m depth (Vs30) at 21 seismograph stations in the eastern United States and find that HVSR peak frequency increases with increasing Vs30. We use this relationship to estimate the National Earthquake Hazards Reduction Program soil class at 218 ANSS (Advanced National Seismic System), GSN (Global Seismographic Network), and RSN (Regional Seismograph Networks) locations in the eastern United States, and suggest that this seismic station–based HVSR proxy could potentially be used to calibrate other site response characterization methods commonly used to estimate shaking hazard.

Mitigation of the consequence of seismically induced damage on a utility water network by means of next generation SCADA

NASA Astrophysics Data System (ADS)

Robertson, Jamie; Shinozuka, Masanobu; Wu, Felix

2011-04-01

When a lifeline system such as a water delivery network is damaged due to a severe earthquake, it is critical to identify its location and extent of the damage in real time in order to minimize the potentially disastrous consequence such damage could otherwise entail. This paper demonstrates how the degree of such minimization can be estimated qualitatively by using the water delivery system of Irvine Water Ranch District (IRWD) as testbed, when it is subjected to magnitude 6.6 San Joaquin Hills Earthquake. In this demonstration, we consider two cases when the IRWD system is equipped or not equipped with a next generation SCADA which consists of a network of MEMS acceleration sensors densely populated and optimally located. These sensors are capable of identifying the location and extent of the damage as well as transmitting the data to the SCADA center for monitoring and control.

Experimental damage detection of wind turbine blade using thin film sensor array

NASA Astrophysics Data System (ADS)

Downey, Austin; Laflamme, Simon; Ubertini, Filippo; Sarkar, Partha

2017-04-01

Damage detection of wind turbine blades is difficult due to their large sizes and complex geometries. Additionally, economic restraints limit the viability of high-cost monitoring methods. While it is possible to monitor certain global signatures through modal analysis, obtaining useful measurements over a blade's surface using off-the-shelf sensing technologies is difficult and typically not economical. A solution is to deploy dedicated sensor networks fabricated from inexpensive materials and electronics. The authors have recently developed a novel large-area electronic sensor measuring strain over very large surfaces. The sensing system is analogous to a biological skin, where local strain can be monitored over a global area. In this paper, we propose the utilization of a hybrid dense sensor network of soft elastomeric capacitors to detect, localize, and quantify damage, and resistive strain gauges to augment such dense sensor network with high accuracy data at key locations. The proposed hybrid dense sensor network is installed inside a wind turbine blade model and tested in a wind tunnel to simulate an operational environment. Damage in the form of changing boundary conditions is introduced into the monitored section of the blade. Results demonstrate the ability of the hybrid dense sensor network, and associated algorithms, to detect, localize, and quantify damage.

Executive attention and personality variables in patients with frontal lobe damage.

PubMed

Rodríguez-Bailón, María; Triviño, Mónica; Lupiáñez, Juan

2012-11-01

Executive Control is required to deal with novel situations or when an action plan is needed. This study aimed to highlight the executive attention deficits of patients with frontal lobe damage. To do so, the ANT-I task (Attention Network Test-Interactions) was administered for the first time to a group of 9 patients with frontal damage caused by traumatic brain injury (TBI) and a matched control group. This task made it possible to measure the three attentional networks proposed by Posner and Dehaene (1994) and their interactions. Results on the alerting and orienting networks did not show any significant differences between the groups. However, a significant effect of group on the executive control network was observed. In addition, participants' personality was assessed with a clinical inventory (the Millon Personality Inventory) that showed a significant positive correlation between borderline personality disorder and the conflict index. These results suggest that frontal lobe damage causes an exclusive impairment in the conflict resolution network that is related to personality traits characterized by a lack of behavioral control. More research will be necessary to study this causal relationship.

Failure and recovery in dynamical networks.

PubMed

Böttcher, L; Luković, M; Nagler, J; Havlin, S; Herrmann, H J

2017-02-03

Failure, damage spread and recovery crucially underlie many spatially embedded networked systems ranging from transportation structures to the human body. Here we study the interplay between spontaneous damage, induced failure and recovery in both embedded and non-embedded networks. In our model the network's components follow three realistic processes that capture these features: (i) spontaneous failure of a component independent of the neighborhood (internal failure), (ii) failure induced by failed neighboring nodes (external failure) and (iii) spontaneous recovery of a component. We identify a metastable domain in the global network phase diagram spanned by the model's control parameters where dramatic hysteresis effects and random switching between two coexisting states are observed. This dynamics depends on the characteristic link length of the embedded system. For the Euclidean lattice in particular, hysteresis and switching only occur in an extremely narrow region of the parameter space compared to random networks. We develop a unifying theory which links the dynamics of our model to contact processes. Our unifying framework may help to better understand controllability in spatially embedded and random networks where spontaneous recovery of components can mitigate spontaneous failure and damage spread in dynamical networks.

Development and Flight Testing of a Neural Network Based Flight Control System on the NF-15B Aircraft

NASA Technical Reports Server (NTRS)

Bomben, Craig R.; Smolka, James W.; Bosworth, John T.; Silliams-Hayes, Peggy S.; Burken, John J.; Larson, Richard R.; Buschbacher, Mark J.; Maliska, Heather A.

2006-01-01

The Intelligent Flight Control System (IFCS) project at the NASA Dryden Flight Research Center, Edwards AFB, CA, has been investigating the use of neural network based adaptive control on a unique NF-15B test aircraft. The IFCS neural network is a software processor that stores measured aircraft response information to dynamically alter flight control gains. In 2006, the neural network was engaged and allowed to learn in real time to dynamically alter the aircraft handling qualities characteristics in the presence of actual aerodynamic failure conditions injected into the aircraft through the flight control system. The use of neural network and similar adaptive technologies in the design of highly fault and damage tolerant flight control systems shows promise in making future aircraft far more survivable than current technology allows. This paper will present the results of the IFCS flight test program conducted at the NASA Dryden Flight Research Center in 2006, with emphasis on challenges encountered and lessons learned.

Sensitivity of directed networks to the addition and pruning of edges and vertices

NASA Astrophysics Data System (ADS)

Goltsev, A. V.; Timár, G.; Mendes, J. F. F.

2017-08-01

Directed networks have various topologically different extensive components, in contrast to a single giant component in undirected networks. We study the sensitivity (response) of the sizes of these extensive components in directed complex networks to the addition and pruning of edges and vertices. We introduce the susceptibility, which quantifies this sensitivity. We show that topologically different parts of a directed network have different sensitivity to the addition and pruning of edges and vertices and, therefore, they are characterized by different susceptibilities. These susceptibilities diverge at the critical point of the directed percolation transition, signaling the appearance (or disappearance) of the giant strongly connected component in the infinite size limit. We demonstrate this behavior in randomly damaged real and synthetic directed complex networks, such as the World Wide Web, Twitter, the Caenorhabditis elegans neural network, directed Erdős-Rényi graphs, and others. We reveal a nonmonotonic dependence of the sensitivity to random pruning of edges or vertices in the case of C. elegans and Twitter that manifests specific structural peculiarities of these networks. We propose the measurements of the susceptibilities during the addition or pruning of edges and vertices as a new method for studying structural peculiarities of directed networks.

Optimal Phase Oscillatory Network

NASA Astrophysics Data System (ADS)

Follmann, Rosangela

2013-03-01

Important topics as preventive detection of epidemics, collective self-organization, information flow and systemic robustness in clusters are typical examples of processes that can be studied in the context of the theory of complex networks. It is an emerging theory in a field, which has recently attracted much interest, involving the synchronization of dynamical systems associated to nodes, or vertices, of the network. Studies have shown that synchronization in oscillatory networks depends not only on the individual dynamics of each element, but also on the combination of the topology of the connections as well as on the properties of the interactions of these elements. Moreover, the response of the network to small damages, caused at strategic points, can enhance the global performance of the whole network. In this presentation we explore an optimal phase oscillatory network altered by an additional term in the coupling function. The application to associative-memory network shows improvement on the correct information retrieval as well as increase of the storage capacity. The inclusion of some small deviations on the nodes, when solutions are attracted to a false state, results in additional enhancement of the performance of the associative-memory network. Supported by FAPESP - Sao Paulo Research Foundation, grant number 2012/12555-4

Network traffic anomaly prediction using Artificial Neural Network

NASA Astrophysics Data System (ADS)

Ciptaningtyas, Hening Titi; Fatichah, Chastine; Sabila, Altea

2017-03-01

As the excessive increase of internet usage, the malicious software (malware) has also increase significantly. Malware is software developed by hacker for illegal purpose(s), such as stealing data and identity, causing computer damage, or denying service to other user[1]. Malware which attack computer or server often triggers network traffic anomaly phenomena. Based on Sophos's report[2], Indonesia is the riskiest country of malware attack and it also has high network traffic anomaly. This research uses Artificial Neural Network (ANN) to predict network traffic anomaly based on malware attack in Indonesia which is recorded by Id-SIRTII/CC (Indonesia Security Incident Response Team on Internet Infrastructure/Coordination Center). The case study is the highest malware attack (SQL injection) which has happened in three consecutive years: 2012, 2013, and 2014[4]. The data series is preprocessed first, then the network traffic anomaly is predicted using Artificial Neural Network and using two weight update algorithms: Gradient Descent and Momentum. Error of prediction is calculated using Mean Squared Error (MSE) [7]. The experimental result shows that MSE for SQL Injection is 0.03856. So, this approach can be used to predict network traffic anomaly.

Current concepts for the combined treatment modality of ionizing radiation with anticancer agents.

PubMed

Oehler, Christoph; Dickinson, Daniel J; Broggini-Tenzer, Angela; Hofstetter, Barbara; Hollenstein, Andreas; Riesterer, Oliver; Vuong, Van; Pruschy, Martin

2007-01-01

In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's.

Coordination of frontline defense mechanisms under severe oxidative stress.

PubMed

Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

2010-07-01

Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays.

Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans

PubMed Central

Jung, Kwang-Woo; Yang, Dong-Hoon; Kim, Min-Kyu; Seo, Ho Seong

2016-01-01

ABSTRACT The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans. PMID:27899501

Apigenin induces DNA damage through the PKCδ-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair

PubMed Central

Arango, Daniel; Parihar, Arti; Villamena, Frederick A.; Wang, Liwen; Freitas, Michael A.; Grotewold, Erich; Doseff, Andrea I.

2014-01-01

Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti-carcinogenic activities through mechanisms yet not fully defined. In the present study, we show that the treatment of leukemia cells with apigenin resulted in the induction of DNA damage preceding the activation of the apoptotic program. Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta (PKCδ), yet was independent of reactive oxygen species or caspase activity. Treatment of monocytic leukemia cells with apigenin induced the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key regulators of the DNA damage response, without affecting the ataxia-telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and pharmacological inhibition of PKCδ abrogated ATM and H2AX phosphorylation, whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We established that apigenin delayed cell cycle progression at G1/S and increased the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that apigenin-induced DNA damage led to down-regulation of genes involved in cell-cycle control and DNA repair. Taken together, the present results show that the PKCδ-dependent activation of ATM and H2AX define the signaling networks responsible for the regulation of DNA damage promoting genome-wide mRNA alterations that result in cell cycle arrest, hence contributing to the anti-carcinogenic activities of this flavonoid. PMID:22985621

Utilizing Maximal Independent Sets as Dominating Sets in Scale-Free Networks

NASA Astrophysics Data System (ADS)

Derzsy, N.; Molnar, F., Jr.; Szymanski, B. K.; Korniss, G.

Dominating sets provide key solution to various critical problems in networked systems, such as detecting, monitoring, or controlling the behavior of nodes. Motivated by graph theory literature [Erdos, Israel J. Math. 4, 233 (1966)], we studied maximal independent sets (MIS) as dominating sets in scale-free networks. We investigated the scaling behavior of the size of MIS in artificial scale-free networks with respect to multiple topological properties (size, average degree, power-law exponent, assortativity), evaluated its resilience to network damage resulting from random failure or targeted attack [Molnar et al., Sci. Rep. 5, 8321 (2015)], and compared its efficiency to previously proposed dominating set selection strategies. We showed that, despite its small set size, MIS provides very high resilience against network damage. Using extensive numerical analysis on both synthetic and real-world (social, biological, technological) network samples, we demonstrate that our method effectively satisfies four essential requirements of dominating sets for their practical applicability on large-scale real-world systems: 1.) small set size, 2.) minimal network information required for their construction scheme, 3.) fast and easy computational implementation, and 4.) resiliency to network damage. Supported by DARPA, DTRA, and NSF.

Resumption of dynamism in damaged networks of coupled oscillators

NASA Astrophysics Data System (ADS)

Kundu, Srilena; Majhi, Soumen; Ghosh, Dibakar

2018-05-01

Deterioration in dynamical activities may come up naturally or due to environmental influences in a massive portion of biological and physical systems. Such dynamical degradation may have outright effect on the substantive network performance. This requires us to provide some proper prescriptions to overcome undesired circumstances. In this paper, we present a scheme based on external feedback that can efficiently revive dynamism in damaged networks of active and inactive oscillators and thus enhance the network survivability. Both numerical and analytical investigations are performed in order to verify our claim. We also provide a comparative study on the effectiveness of this mechanism for feedbacks to the inactive group or to the active group only. Most importantly, resurrection of dynamical activity is realized even in time-delayed damaged networks, which are considered to be less persistent against deterioration in the form of inactivity in the oscillators. Furthermore, prominence in our approach is substantiated by providing evidence of enhanced network persistence in complex network topologies taking small-world and scale-free architectures, which makes the proposed remedy quite general. Besides the study in the network of Stuart-Landau oscillators, affirmative influence of external feedback has been justified in the network of chaotic Rössler systems as well.

Seismic design and engineering research at the U.S. Geological Survey

USGS Publications Warehouse

1988-01-01

The Engineering Seismology Element of the USGS Earthquake Hazards Reduction Program is responsible for the coordination and operation of the National Strong Motion Network to collect, process, and disseminate earthquake strong-motion data; and, the development of improved methodologies to estimate and predict earthquake ground motion.  Instrumental observations of strong ground shaking induced by damaging earthquakes and the corresponding response of man-made structures provide the basis for estimating the severity of shaking from future earthquakes, for earthquake-resistant design, and for understanding the physics of seismologic failure in the Earth's crust.

System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability*

PubMed Central

Xiao, Zhenyu; Chang, Jer-Gung; Hendriks, Ivo A.; Sigurðsson, Jón Otti; Olsen, Jesper V.; Vertegaal, Alfred C.O.

2015-01-01

Genotoxic agents can cause replication fork stalling in dividing cells because of DNA lesions, eventually leading to replication fork collapse when the damage is not repaired. Small Ubiquitin-like Modifiers (SUMOs) are known to counteract replication stress, nevertheless, only a small number of relevant SUMO target proteins are known. To address this, we have purified and identified SUMO-2 target proteins regulated by replication stress in human cells. The developed methodology enabled single step purification of His10-SUMO-2 conjugates under denaturing conditions with high yield and high purity. Following statistical analysis on five biological replicates, a total of 566 SUMO-2 targets were identified. After 2 h of hydroxyurea treatment, 10 proteins were up-regulated for SUMOylation and two proteins were down-regulated for SUMOylation, whereas after 24 h, 35 proteins were up-regulated for SUMOylation, and 13 proteins were down-regulated for SUMOylation. A site-specific approach was used to map over 1000 SUMO-2 acceptor lysines in target proteins. The methodology is generic and is widely applicable in the ubiquitin field. A large subset of these identified proteins function in one network that consists of interacting replication factors, transcriptional regulators, DNA damage response factors including MDC1, ATR-interacting protein ATRIP, the Bloom syndrome protein and the BLM-binding partner RMI1, the crossover junction endonuclease EME1, BRCA1, and CHAF1A. Furthermore, centromeric proteins and signal transducers were dynamically regulated by SUMOylation upon replication stress. Our results uncover a comprehensive network of SUMO target proteins dealing with replication damage and provide a framework for detailed understanding of the role of SUMOylation to counteract replication stress. Ultimately, our study reveals how a post-translational modification is able to orchestrate a large variety of different proteins to integrate different nuclear processes with the aim of dealing with the induced DNA damage. PMID:25755297

Vibrational Analysis of Engine Components Using Neural-Net Processing and Electronic Holography

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Fite, E. Brian; Mehmed, Oral; Thorp, Scott A.

1997-01-01

The use of computational-model trained artificial neural networks to acquire damage specific information from electronic holograms is discussed. A neural network is trained to transform two time-average holograms into a pattern related to the bending-induced-strain distribution of the vibrating component. The bending distribution is very sensitive to component damage unlike the characteristic fringe pattern or the displacement amplitude distribution. The neural network processor is fast for real-time visualization of damage. The two-hologram limit makes the processor more robust to speckle pattern decorrelation. Undamaged and cracked cantilever plates serve as effective objects for testing the combination of electronic holography and neural-net processing. The requirements are discussed for using finite-element-model trained neural networks for field inspections of engine components. The paper specifically discusses neural-network fringe pattern analysis in the presence of the laser speckle effect and the performances of two limiting cases of the neural-net architecture.

Vibrational Analysis of Engine Components Using Neural-Net Processing and Electronic Holography

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Fite, E. Brian; Mehmed, Oral; Thorp, Scott A.

1998-01-01

The use of computational-model trained artificial neural networks to acquire damage specific information from electronic holograms is discussed. A neural network is trained to transform two time-average holograms into a pattern related to the bending-induced-strain distribution of the vibrating component. The bending distribution is very sensitive to component damage unlike the characteristic fringe pattern or the displacement amplitude distribution. The neural network processor is fast for real-time visualization of damage. The two-hologram limit makes the processor more robust to speckle pattern decorrelation. Undamaged and cracked cantilever plates serve as effective objects for testing the combination of electronic holography and neural-net processing. The requirements are discussed for using finite-element-model trained neural networks for field inspections of engine components. The paper specifically discusses neural-network fringe pattern analysis in the presence of the laser speckle effect and the performances of two limiting cases of the neural-net architecture.

Fukunaga-Koontz feature transformation for statistical structural damage detection and hierarchical neuro-fuzzy damage localisation

NASA Astrophysics Data System (ADS)

Hoell, Simon; Omenzetter, Piotr

2017-07-01

Considering jointly damage sensitive features (DSFs) of signals recorded by multiple sensors, applying advanced transformations to these DSFs and assessing systematically their contribution to damage detectability and localisation can significantly enhance the performance of structural health monitoring systems. This philosophy is explored here for partial autocorrelation coefficients (PACCs) of acceleration responses. They are interrogated with the help of the linear discriminant analysis based on the Fukunaga-Koontz transformation using datasets of the healthy and selected reference damage states. Then, a simple but efficient fast forward selection procedure is applied to rank the DSF components with respect to statistical distance measures specialised for either damage detection or localisation. For the damage detection task, the optimal feature subsets are identified based on the statistical hypothesis testing. For damage localisation, a hierarchical neuro-fuzzy tool is developed that uses the DSF ranking to establish its own optimal architecture. The proposed approaches are evaluated experimentally on data from non-destructively simulated damage in a laboratory scale wind turbine blade. The results support our claim of being able to enhance damage detectability and localisation performance by transforming and optimally selecting DSFs. It is demonstrated that the optimally selected PACCs from multiple sensors or their Fukunaga-Koontz transformed versions can not only improve the detectability of damage via statistical hypothesis testing but also increase the accuracy of damage localisation when used as inputs into a hierarchical neuro-fuzzy network. Furthermore, the computational effort of employing these advanced soft computing models for damage localisation can be significantly reduced by using transformed DSFs.

Simple and efficient self-healing strategy for damaged complex networks

NASA Astrophysics Data System (ADS)

Gallos, Lazaros K.; Fefferman, Nina H.

2015-11-01

The process of destroying a complex network through node removal has been the subject of extensive interest and research. Node loss typically leaves the network disintegrated into many small and isolated clusters. Here we show that these clusters typically remain close to each other and we suggest a simple algorithm that is able to reverse the inflicted damage by restoring the network's functionality. After damage, each node decides independently whether to create a new link depending on the fraction of neighbors it has lost. In addition to relying only on local information, where nodes do not need knowledge of the global network status, we impose the additional constraint that new links should be as short as possible (i.e., that the new edge completes a shortest possible new cycle). We demonstrate that this self-healing method operates very efficiently, both in model and real networks. For example, after removing the most connected airports in the USA, the self-healing algorithm rejoined almost 90% of the surviving airports.

Competitive Cyber-Insurance and Internet Security

NASA Astrophysics Data System (ADS)

Shetty, Nikhil; Schwartz, Galina; Felegyhazi, Mark; Walrand, Jean

This paper investigates how competitive cyber-insurers affect network security and welfare of the networked society. In our model, a user's probability to incur damage (from being attacked) depends on both his security and the network security, with the latter taken by individual users as given. First, we consider cyberinsurers who cannot observe (and thus, affect) individual user security. This asymmetric information causes moral hazard. Then, for most parameters, no equilibrium exists: the insurance market is missing. Even if an equilibrium exists, the insurance contract covers only a minor fraction of the damage; network security worsens relative to the no-insurance equilibrium. Second, we consider insurers with perfect information about their users' security. Here, user security is perfectly enforceable (zero cost); each insurance contract stipulates the required user security. The unique equilibrium contract covers the entire user damage. Still, for most parameters, network security worsens relative to the no-insurance equilibrium. Although cyber-insurance improves user welfare, in general, competitive cyber-insurers fail to improve network security.

Mount St. Helens Quick Response Damage Assessment Using High-Altitude Infrared Photography

NASA Astrophysics Data System (ADS)

Hinkle, Richard E.; Prill, James C.; Pruitt, John R.

1981-11-01

After the destructive volcanic eruption of Mount St. Helens on May 18, 1980, there was a need for a quick response damage assessment. Timeliness of the information was emphasized because of the need to immediately devise land man-agement plans for timber sale operations, rehabilitation efforts, fire protection activities, and areas to be preserved. High-altitude color-infrared photography was collected during May and June by the National Aeronautics and Space Administra-tion (NASA) Ames Research Center (ARC). Interpretation of the photography plus a helicopter trip into the area provided the basis for the construction of 58 map-registered overlays within a 3-week period. These overlays depicted in detail the damage to timber resources, the transportation network, and the watershed. Using the 14 timber loss overlays, U.S. Department of Agriculture (USDA) Forest Service personnel were able to digitize cells depicting ownership, degree of damage, and the preeruption cover classes. These digitized data provided such informa-tion as the total area affected within and outside the national forest, total timber acreage destroyed and damaged, the sizes of timber destroyed, and the acreage of barren land both before and after the eruption. The hydrology and transportation overlays provided information for an alert system to locate areas needing in-depth studies. These problem areas were then studied in detail on low-altitude color photography so that potential erosion sites could receive preventive treatments and essential access roads needed for fire control and timber salvage could be repaired.

A flame burning within.

PubMed

Ferrucci, Luigi; Ble, Alessandro; Bandinelli, Stefania; Lauretani, Fulvio; Suthers, Kristen; Guralnik, Jack M

2004-06-01

Inflammation is a human being's primary defense against threats to homeostasis that are encountered every day. Especially in old age, when regulatory mechanisms responsible for inflammatory responses may be ineffective or damaged, the result can be adverse pathological conditions, and an increased risk of morbidity and mortality. The inflammation response is a plastic network composed of redundant signaling among several different mediators. These mediators have a reciprocal relationship with other biological sub-systems, including hormone regulation, the autonomic nervous system, and oxidative/anti-oxidant balance. Studying this complex architecture requires parallel and multiple research strategies from epidemiological to biochemical level, from observational studies to innovative intervention approaches. Given that the inflammatory response is a critical age-related process, understanding its regulatory action is essential in avoiding hazardous consequences in old age.

Innate Immune Regulations and Liver Ischemia Reperfusion Injury

PubMed Central

Lu, Ling; Zhou, Haoming; Ni, Ming; Wang, Xuehao; Busuttil, Ronald; Kupiec-Weglinski, Jerzy; Zhai, Yuan

2016-01-01

Liver ischemia reperfusion activates innate immune system to drive the full development of inflammatory hepatocellular injury. Damage-associated molecular patterns (DAMPs) stimulate myeloid and dendritic cells via pattern recognition receptors (PRRs) to initiate the immune response. Complex intracellular signaling network transduces inflammatory signaling to regulate both innate immune cell activation and parenchymal cell death. Recent studies have revealed that DAMPs may trigger not only proinflammatory, but also immune regulatory responses by activating different PRRs or distinctive intracellular signaling pathways or in special cell populations. Additionally, tissue injury milieu activates PRR-independent receptors which also regulate inflammatory disease processes. Thus, the innate immune mechanism of liver IRI involves diverse molecular and cellular interactions, subjected to both endogenous and exogenous regulation in different cells. A better understanding of these complicated regulatory pathways/network is imperative for us in designing safe and effective therapeutic strategy to ameliorate liver IRI in patients. PMID:27861288

Pattern Learning, Damage and Repair within Biological Neural Networks

NASA Astrophysics Data System (ADS)

Siu, Theodore; Fitzgerald O'Neill, Kate; Shinbrot, Troy

2015-03-01

Traumatic brain injury (TBI) causes damage to neural networks, potentially leading to disability or even death. Nearly one in ten of these patients die, and most of the remainder suffer from symptoms ranging from headaches and nausea to convulsions and paralysis. In vitro studies to develop treatments for TBI have limited in vivo applicability, and in vitro therapies have even proven to worsen the outcome of TBI patients. We propose that this disconnect between in vitro and in vivo outcomes may be associated with the fact that in vitro tests assess indirect measures of neuronal health, but do not investigate the actual function of neuronal networks. Therefore in this talk, we examine both in vitro and in silico neuronal networks that actually perform a function: pattern identification. We allow the networks to execute genetic, Hebbian, learning, and additionally, we examine the effects of damage and subsequent repair within our networks. We show that the length of repaired connections affects the overall pattern learning performance of the network and we propose therapies that may improve function following TBI in clinical settings.

Characterization of the Burkholderia thailandensis SOS Response by Using Whole-Transcriptome Shotgun Sequencing

PubMed Central

Ulrich, Ricky L.; DeShazer, David; Kenny, Tara A.; Ulrich, Melanie P.; Moravusova, Anna; Opperman, Timothy; Bavari, Sina; Bowlin, Terry L.; Moir, Donald T.

2013-01-01

The bacterial SOS response is a well-characterized regulatory network encoded by most prokaryotic bacterial species and is involved in DNA repair. In addition to nucleic acid repair, the SOS response is involved in pathogenicity, stress-induced mutagenesis, and the emergence and dissemination of antibiotic resistance. Using high-throughput sequencing technology (SOLiD RNA-Seq), we analyzed the Burkholderia thailandensis global SOS response to the fluoroquinolone antibiotic, ciprofloxacin (CIP), and the DNA-damaging chemical, mitomycin C (MMC). We demonstrate that a B. thailandensis recA mutant (RU0643) is ∼4-fold more sensitive to CIP in contrast to the parental strain B. thailandensis DW503. Our RNA-Seq results show that CIP and MMC treatment (P < 0.01) resulted in the differential expression of 344 genes in B. thailandensis and 210 genes in RU0643. Several genes associated with the SOS response were induced and include lexA, uvrA, dnaE, dinB, recX, and recA. At the genome-wide level, we found an overall decrease in gene expression, especially for genes involved in amino acid and carbohydrate transport and metabolism, following both CIP and MMC exposure. Interestingly, we observed the upregulation of several genes involved in bacterial motility and enhanced transcription of a B. thailandensis genomic island encoding a Siphoviridae bacteriophage designated ϕE264. Using B. thailandensis plaque assays and PCR with B. mallei ATCC 23344 as the host, we demonstrate that CIP and MMC exposure in B. thailandensis DW503 induces the transcription and translation of viable bacteriophage in a RecA-dependent manner. This is the first report of the SOS response in Burkholderia spp. to DNA-damaging agents. We have identified both common and unique adaptive responses of B. thailandensis to chemical stress and DNA damage. PMID:23872555

Characterization of the Burkholderia thailandensis SOS response by using whole-transcriptome shotgun sequencing.

PubMed

Ulrich, Ricky L; Deshazer, David; Kenny, Tara A; Ulrich, Melanie P; Moravusova, Anna; Opperman, Timothy; Bavari, Sina; Bowlin, Terry L; Moir, Donald T; Panchal, Rekha G

2013-10-01

The bacterial SOS response is a well-characterized regulatory network encoded by most prokaryotic bacterial species and is involved in DNA repair. In addition to nucleic acid repair, the SOS response is involved in pathogenicity, stress-induced mutagenesis, and the emergence and dissemination of antibiotic resistance. Using high-throughput sequencing technology (SOLiD RNA-Seq), we analyzed the Burkholderia thailandensis global SOS response to the fluoroquinolone antibiotic, ciprofloxacin (CIP), and the DNA-damaging chemical, mitomycin C (MMC). We demonstrate that a B. thailandensis recA mutant (RU0643) is ∼4-fold more sensitive to CIP in contrast to the parental strain B. thailandensis DW503. Our RNA-Seq results show that CIP and MMC treatment (P < 0.01) resulted in the differential expression of 344 genes in B. thailandensis and 210 genes in RU0643. Several genes associated with the SOS response were induced and include lexA, uvrA, dnaE, dinB, recX, and recA. At the genome-wide level, we found an overall decrease in gene expression, especially for genes involved in amino acid and carbohydrate transport and metabolism, following both CIP and MMC exposure. Interestingly, we observed the upregulation of several genes involved in bacterial motility and enhanced transcription of a B. thailandensis genomic island encoding a Siphoviridae bacteriophage designated E264. Using B. thailandensis plaque assays and PCR with B. mallei ATCC 23344 as the host, we demonstrate that CIP and MMC exposure in B. thailandensis DW503 induces the transcription and translation of viable bacteriophage in a RecA-dependent manner. This is the first report of the SOS response in Burkholderia spp. to DNA-damaging agents. We have identified both common and unique adaptive responses of B. thailandensis to chemical stress and DNA damage.

Cascading failures in interconnected networks with dynamical redistribution of loads

NASA Astrophysics Data System (ADS)

Zhao, Zhuang; Zhang, Peng; Yang, Hujiang

2015-09-01

Cascading failures of loads in isolated networks and coupled networks have been studied in the past few years. In most of the corresponding results, the topologies of the networks are destroyed. Here, we present an interconnected network model considering cascading failures based on the dynamic redistribution of flow in the networks. Compared with the results of single scale-free networks, we find that interconnected scale-free networks have higher vulnerability. Additionally, the network heterogeneity plays an important role in the robustness of interconnected networks under intentional attacks. Considering the effects of various coupling preferences, the results show that there are almost no differences. Finally, the application of our model to the Beijing interconnected traffic network, which consists of a subway network and a bus network, shows that the subway network suffers more damage under the attack. Moreover, the interconnected traffic network may be more exposed to damage after initial attacks on the bus network. These discussions are important for the design and optimization of interconnected networks.

Equation of State and Damage in Polyethylene

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

Coe, Joshua Damon; Brown, Eric; Cady, Carl Mcelhinney

The dynamic response of polymers differs significantly from those of metals, upon which many of the National Laboratories' deformation, damage, and failure models are based. Their moduli, yield strength, and damage characteristics are highly strain rate-, temperature-, and phase-dependent, requiring models that encompass a wide range of phenomena including some not in equilibrium. Recently, Los Alamos developed the Glassy Amorphous Polymer (GAP) 1 model [1] to address limitations in existing models of polymer deformation. GAP captures both volumetric (equation of state) and deviatoric (shear) response, including a non-equilibrium component to the former (a feature determined to be crucial in capturingmore » the low-pressure, viscoelastic response to impact loading). GAP has already been applied to polymers such as PMMA, PTFE, epoxy, and Kel-F 800, but with an emphasis on impact response as opposed to damage or failure. The current effort was launched to address this gap in predictive capability. For reasons that will be made clear, semi-crystalline polyethylene (PE) was chosen to serve as a model system for parameterization and validation. PE (-C 2H 4-)n is one of the most widely used polymers in industrial and engineering contexts, chiey due to the versatility of its mechanical response. This response can be tuned through network and chain structure, degree of crystallinity, and molecular weight. PE is found in several forms including low density (LDPE), high density (HDPE), and ultra-high molecular weight (UHMWPE). The focus here was on HDPE and UHMWPE, of pedigree described in the following section. Materials were well-characterized prior to study and are representative of semi-crystalline polymers of interest to DOE and DoD. Semi-crystalline PE undergoes a glass transition at low temperature (-35°C) and melts across a range of moderate temperatures (~80-180°C), depending on its structure. It is typically inert chemically, has low strength and high ductility, and the high strength and anisotropy of UHMWPE ber, in particular, have driven its use in engineering, impact, and armor applications. Surprisingly little is known, however, about the influence of PE's crystalline structure and associated phase transitions (including melt) on its response to dynamic compression. A broad suite of experiments was used to calibrate the GAP model for HDPE and UHMWPE. Section IV examines the effects of tensile strain on the structure and integrity of PE crystalline domains. These data were used to inform the preliminary damage model described in Section XII, whose roots lie in statistical physics and network theory. The viscoelastic and plastic components of GAP rely heavily on the stress-strain data of Section VI, which also include dynamic extrusion and Taylor anvil experiments used to validate the damage model. The thermal data of Section X provide crucial inputs to the equilibrium EOS in GAP, as well as the much broader range SESAME EOS whose construction is outlined in Section XI. Section VII details plate impact experiments characterizing the low-pressure shock locus and failure (spall) using in situ electromagnetic gauges. A previously reported \\cusp" in the principal Hugoniot near 0.5 kbar was confirmed, and a multi-wave structure was observed over a limited input stress range above the cusp. This cusp is believed due to solid-solid phase transitions associated with the crystalline domains of the polymer.« less

Detection and Prediction of Hail Storms in Satellite Imagery using Deep Learning

NASA Astrophysics Data System (ADS)

Pullman, M.; Gurung, I.; Ramachandran, R.; Maskey, M.

2017-12-01

Natural hazards, such as damaging hail storms, dramatically disrupt both industry and agriculture, having significant socio-economic impacts in the United States. In 2016, hail was responsible for 3.5 billion and 23 million dollars in damage to property and crops, respectively, making it the second costliest 2016 weather phenomenon in the United States. The destructive nature and high cost of hail storms has driven research into the development of more accurate hail-prediction algorithms in an effort to mitigate societal impacts. Recently, weather forecasting efforts have turned to deep learning neural networks because neural networks can more effectively model complex, nonlinear, dynamical phenomenon that exist in large datasets through multiple stages of transformation and representation. In an effort to improve hail-prediction techniques, we propose a deep learning technique that leverages satellite imagery to detect and predict the occurrence of hail storms. The technique is applied to satellite imagery from 2006 to 2016 for the contiguous United States and incorporates hail reports obtained from the National Center for Environmental Information Storm Events Database for training and validation purposes. In this presentation, we describe a novel approach to predicting hail via a neural network model that creates a large labeled dataset of hail storms, the accuracy and results of the model, and its applications for improving hail forecasting.

Surface water floods in Switzerland: what insurance claim records tell us about the damage in space and time

NASA Astrophysics Data System (ADS)

Bernet, Daniel B.; Prasuhn, Volker; Weingartner, Rolf

2017-09-01

Surface water floods (SWFs) have received increasing attention in the recent years. Nevertheless, we still know relatively little about where, when and why such floods occur and cause damage, largely due to a lack of data but to some degree also because of terminological ambiguities. Therefore, in a preparatory step, we summarize related terms and identify the need for unequivocal terminology across disciplines and international boundaries in order to bring the science together. Thereafter, we introduce a large (n = 63 117), long (10-33 years) and representative (48 % of all Swiss buildings covered) data set of spatially explicit Swiss insurance flood claims. Based on registered flood damage to buildings, the main aims of this study are twofold: First, we introduce a method to differentiate damage caused by SWFs and fluvial floods based on the geographical location of each damaged object in relation to flood hazard maps and the hydrological network. Second, we analyze the data with respect to their spatial and temporal distributions aimed at quantitatively answering the fundamental questions of how relevant SWF damage really is, as well as where and when it occurs in space and time. This study reveals that SWFs are responsible for at least 45 % of the flood damage to buildings and 23 % of the associated direct tangible losses, whereas lower losses per claim are responsible for the lower loss share. The Swiss lowlands are affected more heavily by SWFs than the alpine regions. At the same time, the results show that the damage claims and associated losses are not evenly distributed within each region either. Damage caused by SWFs occurs by far most frequently in summer in almost all regions. The normalized SWF damage of all regions shows no significant upward trend between 1993 and 2013. We conclude that SWFs are in fact a highly relevant process in Switzerland that should receive similar attention like fluvial flood hazards. Moreover, as SWF damage almost always coincides with fluvial flood damage, we suggest considering SWFs, like fluvial floods, as integrated processes of our catchments.

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica

PubMed Central

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds. PMID:26784887

SOS System Induction Inhibits the Assembly of Chemoreceptor Signaling Clusters in Salmonella enterica.

PubMed

Irazoki, Oihane; Mayola, Albert; Campoy, Susana; Barbé, Jordi

2016-01-01

Swarming, a flagellar-driven multicellular form of motility, is associated with bacterial virulence and increased antibiotic resistance. In this work we demonstrate that activation of the SOS response reversibly inhibits swarming motility by preventing the assembly of chemoreceptor-signaling polar arrays. We also show that an increase in the concentration of the RecA protein, generated by SOS system activation, rather than another function of this genetic network impairs chemoreceptor polar cluster formation. Our data provide evidence that the molecular balance between RecA and CheW proteins is crucial to allow polar cluster formation in Salmonella enterica cells. Thus, activation of the SOS response by the presence of a DNA-injuring compound increases the RecA concentration, thereby disturbing the equilibrium between RecA and CheW and resulting in the cessation of swarming. Nevertheless, when the DNA-damage decreases and the SOS response is no longer activated, basal RecA levels and thus polar cluster assembly are reestablished. These results clearly show that bacterial populations moving over surfaces make use of specific mechanisms to avoid contact with DNA-damaging compounds.

Simulating Impacts of Disruptions to Liquid Fuels Infrastructure

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

Wilson, Michael; Corbet, Thomas F.; Baker, Arnold B.

This report presents a methodology for estimating the impacts of events that damage or disrupt liquid fuels infrastructure. The impact of a disruption depends on which components of the infrastructure are damaged, the time required for repairs, and the position of the disrupted components in the fuels supply network. Impacts are estimated for seven stressing events in regions of the United States, which were selected to represent a range of disruption types. For most of these events the analysis is carried out using the National Transportation Fuels Model (NTFM) to simulate the system-level liquid fuels sector response. Results are presentedmore » for each event, and a brief cross comparison of event simulation results is provided.« less

Inhibiting ethylene perception with 1-methylcyclopropene triggers molecular responses aimed to cope with cell toxicity and increased respiration in citrus fruits.

PubMed

Establés-Ortiz, Beatriz; Romero, Paco; Ballester, Ana-Rosa; González-Candelas, Luis; Lafuente, María T

2016-06-01

The ethylene perception inhibitor 1-methylcyclopropene (1-MCP) has been critical in understanding the hormone's mode of action. However, 1-MCP may trigger other processes that could vary the interpretation of results related until now to ethylene, which we aim to understand by using transcriptomic analysis. Transcriptomic changes in ethylene and 1-MCP-treated 'Navelate' (Citrus sinensis L. Osbeck) oranges were studied in parallel with changes in ethylene production, respiration and peel damage. The effects of compounds modifying the levels of the ethylene co-product cyanide and nitric oxide (NO) on fruit physiology were also studied. Results suggested that: 1) The ethylene treatment caused sub-lethal stress since it induced stress-related responses and reduced peel damage; 2) 1-MCP induced ethylene-dependent and ethylene-independent responsive networks; 3) 1-MCP triggered ethylene overproduction, stress-related responses and metabolic shifts aimed to cope with cell toxicity, which mostly affected to the inner part of the peel (albedo); 4) 1-MCP increased respiration and drove metabolism reconfiguration for favoring energy conservation but up-regulated genes related to lipid and protein degradation and triggered the over-expression of genes associated with the plasma membrane cellular component; 5) Xenobiotics and/or reactive oxygen species (ROS) might act as signals for defense responses in the ethylene-treated fruit, while their uncontrolled generation would induce processes mimicking cell death and damage in 1-MCP-treated fruit; 6) ROS, the ethylene co-product cyanide and NO may converge in the toxic effects of 1-MCP. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung

PubMed Central

Wirsdörfer, Florian; Jendrossek, Verena

2016-01-01

Radiation-induced pneumonitis and fibrosis are dose-limiting side effects of thoracic irradiation. Thoracic irradiation triggers acute and chronic environmental lung changes that are shaped by the damage response of resident cells, by the resulting reaction of the immune system, and by repair processes. Although considerable progress has been made during the last decade in defining involved effector cells and soluble mediators, the network of pathophysiological events and the cellular cross talk linking acute tissue damage to chronic inflammation and fibrosis still require further definition. Infiltration of cells from the innate and adaptive immune systems is a common response of normal tissues to ionizing radiation. Herein, lymphocytes represent a versatile and wide-ranged group of cells of the immune system that can react under specific conditions in various ways and participate in modulating the lung environment by adopting pro-inflammatory, anti-inflammatory, or even pro- or anti-fibrotic phenotypes. The present review provides an overview on published data about the role of lymphocytes in radiation-induced lung disease and related damage-associated pulmonary diseases with a focus on T lymphocytes and B lymphocytes. We also discuss the suspected dual role of specific lymphocyte subsets during the pneumonitic phase and fibrotic phase that is shaped by the environmental conditions as well as the interaction and the intercellular cross talk between cells from the innate and adaptive immune systems and (damaged) resident epithelial cells and stromal cells (e.g., endothelial cells, mesenchymal stem cells, and fibroblasts). Finally, we highlight potential therapeutic targets suited to counteract pathological lymphocyte responses to prevent or treat radiation-induced lung disease. PMID:28018357

Three-dimensional characterization of microporosity and permeability in fault zones hosted in heterolithic succession

NASA Astrophysics Data System (ADS)

Riegel, H. B.; Zambrano, M.; Jablonska, D.; Emanuele, T.; Agosta, F.; Mattioni, L.; Rustichelli, A.

2017-12-01

The hydraulic properties of fault zones depend upon the individual contributions of the damage zone and the fault core. In the case of the damage zone, it is generally characterized by means of fracture analysis and modelling implementing multiple approaches, for instance the discrete fracture network model, the continuum model, and the channel network model. Conversely, the fault core is more difficult to characterize because it is normally composed of fine grain material generated by friction and wear. If the dimensions of the fault core allows it, the porosity and permeability are normally studied by means of laboratory analysis or in the other case by two dimensional microporosity analysis and in situ measurements of permeability (e.g. micro-permeameter). In this study, a combined approach consisting of fracture modeling, three-dimensional microporosity analysis, and computational fluid dynamics was applied to characterize the hydraulic properties of fault zones. The studied fault zones crosscut a well-cemented heterolithic succession (sandstone and mudstones) and may vary in terms of fault core thickness and composition, fracture properties, kinematics (normal or strike-slip), and displacement. These characteristics produce various splay and fault core behavior. The alternation of sandstone and mudstone layers is responsible for the concurrent occurrence of brittle (fractures) and ductile (clay smearing) deformation. When these alternating layers are faulted, they produce corresponding fault cores which act as conduits or barriers for fluid migration. When analyzing damage zones, accurate field and data acquisition and stochastic modeling was used to determine the hydraulic properties of the rock volume, in relation to the surrounding, undamaged host rock. In the fault cores, the three-dimensional pore network quantitative analysis based on X-ray microtomography images includes porosity, pore connectivity, and specific surface area. In addition, images were used to perform computational fluid simulation (Lattice-Boltzmann multi relaxation time method) and estimate the permeability. These results will be useful for understanding the deformation process and hydraulic properties across meter-scale damage zones.

[Role of the orbitofrontal cortex in moral judgment].

PubMed

Mimura, Masaru

2010-11-01

The neural substrates of moral judgments have recently been advocated to consist of widely distributed brain networks including the orbitofrontal cortex (OFC), anterior temporal lobe and superior temporal gyrus. Moral judgments could be regarded as a conflict between the top-down rational/logical processes and the bottom-up irrational/emotional processes. Individuals with OFC damage are usually difficult to inhibit emotionally-driven outrages, thereby demonstrating severe impairment of moral judgments despite their well-preserved moral knowledge. Individuals with OFC damage frequently present with anti-social less moral behaviors. However, clinical observation indicates that some OFC patients may show "hypermoral" tendency in the sense that they are too strict to overlook other person's offense. Two representative cases with OFC damage were reported, both presented with extreme rage against others' offensive behaviors. To further elucidate the "hypermorality" of OFC patients, an experiment was performed in which patients with OFC damage and healthy control participants were asked to determine punishments for other's fictitious crimes that varied in perpetrator responsibility and crime severity. Individuals with OFC damage punished more strictly than healthy controls those persons for mitigating circumstances. The results are consistent with clinical observation of OFC patients' highly rigid and inflexible behaviors against third person's offense.

Telomerase reverse transcriptase (TERT) - enhancer of zeste homolog 2 (EZH2) network regulates lipid metabolism and DNA damage responses in glioblastoma.

PubMed

Ahmad, Fahim; Patrick, Shruti; Sheikh, Touseef; Sharma, Vikas; Pathak, Pankaj; Malgulwar, Prit Benny; Kumar, Anupam; Joshi, Shanker Datt; Sarkar, Chitra; Sen, Ellora

2017-12-01

Elevated expression of enhancer of zeste homolog 2 (EZH2), a histone H3K27 methyltransferase, was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the correlation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of human telomerase reverse transcriptase either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased ataxia-telangiectasia-mutated (ATM) phosphorylation levels. Conversely, diminished TERT and FASN levels upon siRNA-mediated EZH2 knockdown indicated a positive correlation between TERT and EZH2. Interestingly, ATM kinase inhibitor rescued TERT inhibition-mediated decrease in FASN and EZH2 levels. Importantly, TERT promoter mutant tumors exhibited greater microsatellite instability, heightened FASN levels and lipid accumulation. Coherent with in vitro findings, pharmacological inhibition of TERT by costunolide decreased lipid accumulation and elevated ATM expression in heterotypic xenograft glioma mouse model. By bringing TERT-EZH2 network at the forefront as driver of dysregulated metabolism, our findings highlight the non-canonical but distinct role of TERT in metabolic reprogramming and DNA damage responses in glioblastoma. © 2017 International Society for Neurochemistry.

Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma Mechanics

PubMed Central

Kraft, Reuben H.; Mckee, Phillip Justin; Dagro, Amy M.; Grafton, Scott T.

2012-01-01

This article presents the integration of brain injury biomechanics and graph theoretical analysis of neuronal connections, or connectomics, to form a neurocomputational model that captures spatiotemporal characteristics of trauma. We relate localized mechanical brain damage predicted from biofidelic finite element simulations of the human head subjected to impact with degradation in the structural connectome for a single individual. The finite element model incorporates various length scales into the full head simulations by including anisotropic constitutive laws informed by diffusion tensor imaging. Coupling between the finite element analysis and network-based tools is established through experimentally-based cellular injury thresholds for white matter regions. Once edges are degraded, graph theoretical measures are computed on the “damaged” network. For a frontal impact, the simulations predict that the temporal and occipital regions undergo the most axonal strain and strain rate at short times (less than 24 hrs), which leads to cellular death initiation, which results in damage that shows dependence on angle of impact and underlying microstructure of brain tissue. The monotonic cellular death relationships predict a spatiotemporal change of structural damage. Interestingly, at 96 hrs post-impact, computations predict no network nodes were completely disconnected from the network, despite significant damage to network edges. At early times () network measures of global and local efficiency were degraded little; however, as time increased to 96 hrs the network properties were significantly reduced. In the future, this computational framework could help inform functional networks from physics-based structural brain biomechanics to obtain not only a biomechanics-based understanding of injury, but also neurophysiological insight. PMID:22915997

Topological resilience in non-normal networked systems

NASA Astrophysics Data System (ADS)

Asllani, Malbor; Carletti, Timoteo

2018-04-01

The network of interactions in complex systems strongly influences their resilience and the system capability to resist external perturbations or structural damages and to promptly recover thereafter. The phenomenon manifests itself in different domains, e.g., parasitic species invasion in ecosystems or cascade failures in human-made networks. Understanding the topological features of the networks that affect the resilience phenomenon remains a challenging goal for the design of robust complex systems. We hereby introduce the concept of non-normal networks, namely networks whose adjacency matrices are non-normal, propose a generating model, and show that such a feature can drastically change the global dynamics through an amplification of the system response to exogenous disturbances and eventually impact the system resilience. This early stage transient period can induce the formation of inhomogeneous patterns, even in systems involving a single diffusing agent, providing thus a new kind of dynamical instability complementary to the Turing one. We provide, first, an illustrative application of this result to ecology by proposing a mechanism to mute the Allee effect and, second, we propose a model of virus spreading in a population of commuters moving using a non-normal transport network, the London Tube.

FIRESTORM: a collaborative network suite application for rapid sensor data processing and precise decisive responses

NASA Astrophysics Data System (ADS)

Kaniyantethu, Shaji

2011-06-01

This paper discusses the many features and composed technologies in Firestorm™ - a Distributed Collaborative Fires and Effects software. Modern response management systems capitalize on the capabilities of a plethora of sensors and its output for situational awareness. Firestorm utilizes a unique networked lethality approach by integrating unmanned air and ground vehicles to provide target handoff and sharing of data between humans and sensors. The system employs Bayesian networks for track management of sensor data, and distributed auction algorithms for allocating targets and delivering the right effect without information overload to the Warfighter. Firestorm Networked Effects Component provides joint weapon-target pairing, attack guidance, target selection standards, and other fires and effects components. Moreover, the open and modular architecture allows for easy integration with new data sources. Versatility and adaptability of the application enable it to devise and dispense a suitable response to a wide variety of scenarios. Recently, this application was used for detecting and countering a vehicle intruder with the help of radio frequency spotter sensor, command driven cameras, remote weapon system, portable vehicle arresting barrier, and an unmanned aerial vehicle - which confirmed the presence of the intruder, as well as provided lethal/non-lethal response and battle damage assessment. The completed demonstrations have proved Firestorm's™ validity and feasibility to predict, detect, neutralize, and protect key assets and/or area against a variety of possible threats. The sensors and responding assets can be deployed with numerous configurations to cover the various terrain and environmental conditions, and can be integrated to a number of platforms.

Alarmins and Their Receptors as Modulators and Indicators of Alloimmune Responses.

PubMed

Matta, B M; Reichenbach, D K; Blazar, B R; Turnquist, H R

2017-02-01

Cell damage and death releases alarmins, self-derived immunomodulatory molecules that recruit and activate the immune system. Unfortunately, numerous processes critical to the transplantation of allogeneic materials result in the destruction of donor and recipient cells and may trigger alarmin release. Alarmins, often described as damage-associated molecular patterns, together with exogenous pathogen-associated molecular patterns, are potent orchestrators of immune responses; however, the precise role that alarmins play in alloimmune responses remains relatively undefined. We examined evolving concepts regarding how alarmins affect solid organ and allogeneic hematopoietic cell transplantation outcomes and the mechanisms by which self molecules are released. We describe how, once released, alarmins may act alone or in conjunction with nonself materials to contribute to cytokine networks controlling alloimmune responses and their intensity. It is becoming recognized that this class of molecules has pleotropic functions, and certain alarmins can promote both inflammatory and regulatory responses in transplant models. Emerging evidence indicates that alarmins and their receptors may be promising transplantation biomarkers. Developing the therapeutic ability to support alarmin regulatory mechanisms and the predictive value of alarmin pathway biomarkers for early intervention may provide opportunities to benefit graft recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chromatin Relaxation-Mediated Induction of p19INK4d Increases the Ability of Cells to Repair Damaged DNA

PubMed Central

Carcagno, Abel L.; Marazita, Mariela C.; Sonzogni, Silvina V.; Ceruti, Julieta M.; Cánepa, Eduardo T.

2013-01-01

The maintenance of genomic integrity is of main importance to the survival and health of organisms which are continuously exposed to genotoxic stress. Cells respond to DNA damage by activating survival pathways consisting of cell cycle checkpoints and repair mechanisms. However, the signal that triggers the DNA damage response is not necessarily a direct detection of the primary DNA lesion. In fact, chromatin defects may serve as initiating signals to activate those mechanisms. If the modulation of chromatin structure could initiate a checkpoint response in a direct manner, this supposes the existence of specific chromatin sensors. p19INK4d, a member of the INK4 cell cycle inhibitors, plays a crucial role in regulating genomic stability and cell viability by enhancing DNA repair. Its expression is induced in cells injured by one of several genotoxic treatments like cis-platin, UV light or neocarzinostatin. Nevertheless, when exogenous DNA damaged molecules are introduced into the cell, this induction is not observed. Here, we show that p19INK4d is enhanced after chromatin relaxation even in the absence of DNA damage. This induction was shown to depend upon ATM/ATR, Chk1/Chk2 and E2F activity, as is the case of p19INK4d induction by endogenous DNA damage. Interestingly, p19INK4d improves DNA repair when the genotoxic damage is caused in a relaxed-chromatin context. These results suggest that changes in chromatin structure, and not DNA damage itself, is the actual trigger of p19INK4d induction. We propose that, in addition to its role as a cell cycle inhibitor, p19INK4d could participate in a signaling network directed to detecting and eventually responding to chromatin anomalies. PMID:23593412

Embedded Carbon Nanotube Networks for Damage Precursor Detection

DTIC Science & Technology

2014-01-01

3Thostenson, E. T.; Chou, T.-W. Carbon Nanotube Networks: Sensing of Distributed Strain and Damage for Life Prediction and Self - Healing . Advanced...3 Figure 2. Rubber dogbone mold...room temperature vulcanizing rubber to create the final mold. The rubber was mixed with Tin NW Catalyst at a 10:1 ratio. The viscous liquid rubber

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Adenovirus Core Protein VII Downregulates the DNA Damage Response on the Host Genome

PubMed Central

Avgousti, Daphne C.; Della Fera, Ashley N.; Otter, Clayton J.; Herrmann, Christin; Pancholi, Neha J.

2017-01-01

ABSTRACT Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein VII, a virally encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by the cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome. Here we show that protein VII at cellular chromatin results in a significant decrease in accumulation of phosphorylated H2AX (γH2AX) following irradiation, indicating that protein VII inhibits DDR signaling. The oncoprotein SET was recently suggested to modulate the DDR by affecting access of repair proteins to chromatin. Since protein VII binds SET, we investigated a role for SET in DDR inhibition by protein VII. We show that knockdown of SET partially rescues the protein VII-induced decrease in γH2AX accumulation on the host genome, suggesting that SET is required for inhibition. Finally, we show that knockdown of SET also allows ATM to localize to incoming viral genomes bound by protein VII during infection with a mutant lacking early region E4. Together, our data suggest that the protein VII-SET interaction contributes to DDR evasion by adenovirus. Our results provide an additional example of a strategy used by adenovirus to abrogate the host DDR and show how viruses can modify cellular processes through manipulation of host chromatin. IMPORTANCE The DNA damage response (DDR) is a cellular network that is crucial for maintaining genome integrity. DNA viruses replicating in the nucleus challenge the resident genome and must overcome cellular responses, including the DDR. Adenoviruses are prevalent human pathogens that can cause a multitude of diseases, such as respiratory infections and conjunctivitis. Here we describe how a small adenovirus core protein that localizes to host chromatin during infection can globally downregulate the DDR. Our study focuses on key players in the damage signaling pathway and highlights how viral manipulation of chromatin may influence access of DDR proteins to the host genome. PMID:28794020

Explaining the heterogeneity of functional connectivity findings in multiple sclerosis: An empirically informed modeling study.

PubMed

Tewarie, Prejaas; Steenwijk, Martijn D; Brookes, Matthew J; Uitdehaag, Bernard M J; Geurts, Jeroen J G; Stam, Cornelis J; Schoonheim, Menno M

2018-06-01

To understand the heterogeneity of functional connectivity results reported in the literature, we analyzed the separate effects of grey and white matter damage on functional connectivity and networks in multiple sclerosis. For this, we employed a biophysical thalamo-cortical model consisting of interconnected cortical and thalamic neuronal populations, informed and amended by empirical diffusion MRI tractography data, to simulate functional data that mimic neurophysiological signals. Grey matter degeneration was simulated by decreasing within population connections and white matter degeneration by lowering between population connections, based on lesion predilection sites in multiple sclerosis. For all simulations, functional connectivity and functional network organization are quantified by phase synchronization and network integration, respectively. Modeling results showed that both cortical and thalamic grey matter damage induced a global increase in functional connectivity, whereas white matter damage induced an initially increased connectivity followed by a global decrease. Both white and especially grey matter damage, however, induced a decrease in network integration. These empirically informed simulations show that specific topology and timing of structural damage are nontrivial aspects in explaining functional abnormalities in MS. Insufficient attention to these aspects likely explains contradictory findings in multiple sclerosis functional imaging studies so far. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Discussion on the Technology and Method of Computer Network Security Management

NASA Astrophysics Data System (ADS)

Zhou, Jianlei

2017-09-01

With the rapid development of information technology, the application of computer network technology has penetrated all aspects of society, changed people's way of life work to a certain extent, brought great convenience to people. But computer network technology is not a panacea, it can promote the function of social development, but also can cause damage to the community and the country. Due to computer network’ openness, easiness of sharing and other characteristics, it had a very negative impact on the computer network security, especially the loopholes in the technical aspects can cause damage on the network information. Based on this, this paper will do a brief analysis on the computer network security management problems and security measures.

A minimal titration model of the mammalian dynamical heat shock response

NASA Astrophysics Data System (ADS)

Sivéry, Aude; Courtade, Emmanuel; Thommen, Quentin

2016-12-01

Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities. This model, which is based on chemical kinetics laws, is kept with a low dimensionality without altering the biological interpretation of the model dynamics. This simplistic model highlights the titration of HSF1 by chaperones as the guiding line of the network. Moreover, by a steady states analysis of the network, three different temperature stress regimes appear: normal, acute, and chronic, where normal stress corresponds to pseudo thermal adaption. The protein triage that governs the fate of damaged proteins or the different stress regimes are consequences of the titration mechanism. The simplicity of the present model is of interest in order to study detailed modelling of cross regulation between the HSR and other major genetic networks like the cell cycle or the circadian clock.

Damage Detection Using Holography and Interferometry

NASA Technical Reports Server (NTRS)

Decker, Arthur J.

2003-01-01

This paper reviews classical approaches to damage detection using laser holography and interferometry. The paper then details the modern uses of electronic holography and neural-net-processed characteristic patterns to detect structural damage. The design of the neural networks and the preparation of the training sets are discussed. The use of a technique to optimize the training sets, called folding, is explained. Then a training procedure is detailed that uses the holography-measured vibration modes of the undamaged structures to impart damage-detection sensitivity to the neural networks. The inspections of an optical strain gauge mounting plate and an International Space Station cold plate are presented as examples.

Hierarchical structural health monitoring system combining a fiber optic spinal cord network and distributed nerve cell devices

NASA Astrophysics Data System (ADS)

Minakuchi, Shu; Tsukamoto, Haruka; Takeda, Nobuo

2009-03-01

This study proposes novel hierarchical sensing concept for detecting damages in composite structures. In the hierarchical system, numerous three-dimensionally structured sensor devices are distributed throughout the whole structural area and connected with the optical fiber network through transducing mechanisms. The distributed "sensory nerve cell" devices detect the damage, and the fiber optic "spinal cord" network gathers damage signals and transmits the information to a measuring instrument. This study began by discussing the basic concept of the hierarchical sensing system thorough comparison with existing fiber optic based systems and nerve systems in the animal kingdom. Then, in order to validate the proposed sensing concept, impact damage detection system for the composite structure was proposed. The sensor devices were developed based on Comparative Vacuum Monitoring (CVM) system and the Brillouin based distributed strain sensing was utilized to gather the damage signals from the distributed devices. Finally a verification test was conducted using prototype devices. Occurrence of barely visible impact damage was successfully detected and it was clearly indicated that the hierarchical system has better repairability, higher robustness, and wider monitorable area compared to existing systems utilizing embedded optical fiber sensors.

Controlling the self-organizing dynamics in a sandpile model on complex networks by failure tolerance

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

Qi, Junjian; Pfenninger, Stefan

In this paper, we propose a strategy to control the self-organizing dynamics of the Bak-Tang-Wiesenfeld (BTW) sandpile model on complex networks by allowing some degree of failure tolerance for the nodes and introducing additional active dissipation while taking the risk of possible node damage. We show that the probability for large cascades significantly increases or decreases respectively when the risk for node damage outweighs the active dissipation and when the active dissipation outweighs the risk for node damage. By considering the potential additional risk from node damage, a non-trivial optimal active dissipation control strategy which minimizes the total cost inmore » the system can be obtained. Under some conditions the introduced control strategy can decrease the total cost in the system compared to the uncontrolled model. Moreover, when the probability of damaging a node experiencing failure tolerance is greater than the critical value, then no matter how successful the active dissipation control is, the total cost of the system will have to increase. This critical damage probability can be used as an indicator of the robustness of a network or system. Copyright (C) EPLA, 2015« less

Coordination of frontline defense mechanisms under severe oxidative stress

PubMed Central

Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

2010-01-01

Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations—this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of γ rays. PMID:20664639

Capturing changes in flood risk with Bayesian approaches for flood damage assessment

NASA Astrophysics Data System (ADS)

Vogel, Kristin; Schröter, Kai; Kreibich, Heidi; Thieken, Annegret; Müller, Meike; Sieg, Tobias; Laudan, Jonas; Kienzler, Sarah; Weise, Laura; Merz, Bruno; Scherbaum, Frank

2016-04-01

Flood risk is a function of hazard as well as of exposure and vulnerability. All three components are under change over space and time and have to be considered for reliable damage estimations and risk analyses, since this is the basis for an efficient, adaptable risk management. Hitherto, models for estimating flood damage are comparatively simple and cannot sufficiently account for changing conditions. The Bayesian network approach allows for a multivariate modeling of complex systems without relying on expert knowledge about physical constraints. In a Bayesian network each model component is considered to be a random variable. The way of interactions between those variables can be learned from observations or be defined by expert knowledge. Even a combination of both is possible. Moreover, the probabilistic framework captures uncertainties related to the prediction and provides a probability distribution for the damage instead of a point estimate. The graphical representation of Bayesian networks helps to study the change of probabilities for changing circumstances and may thus simplify the communication between scientists and public authorities. In the framework of the DFG-Research Training Group "NatRiskChange" we aim to develop Bayesian networks for flood damage and vulnerability assessments of residential buildings and companies under changing conditions. A Bayesian network learned from data, collected over the last 15 years in flooded regions in the Elbe and Danube catchments (Germany), reveals the impact of many variables like building characteristics, precaution and warning situation on flood damage to residential buildings. While the handling of incomplete and hybrid (discrete mixed with continuous) data are the most challenging issues in the study on residential buildings, a similar study, that focuses on the vulnerability of small to medium sized companies, bears new challenges. Relying on a much smaller data set for the determination of the model parameters, overly complex models should be avoided. A so called Markov Blanket approach aims at the identification of the most relevant factors and constructs a Bayesian network based on those findings. With our approach we want to exploit a major advantage of Bayesian networks which is their ability to consider dependencies not only pairwise, but to capture the joint effects and interactions of driving forces. Hence, the flood damage network does not only show the impact of precaution on the building damage separately, but also reveals the mutual effects of precaution and the quality of warning for a variety of flood settings. Thus, it allows for a consideration of changing conditions and different courses of action and forms a novel and valuable tool for decision support. This study is funded by the Deutsche Forschungsgemeinschaft (DFG) within the research training program GRK 2043/1 "NatRiskChange - Natural hazards and risks in a changing world" at the University of Potsdam.

Real-Time Continuous Response Spectra Exceedance Calculation Displayed in a Web-Browser Enables Rapid and Robust Damage Evaluation by First Responders

NASA Astrophysics Data System (ADS)

Franke, M.; Skolnik, D. A.; Harvey, D.; Lindquist, K.

2014-12-01

A novel and robust approach is presented that provides near real-time earthquake alarms for critical structures at distributed locations and large facilities using real-time estimation of response spectra obtained from near free-field motions. Influential studies dating back to the 1980s identified spectral response acceleration as a key ground motion characteristic that correlates well with observed damage in structures. Thus, monitoring and reporting on exceedance of spectra-based thresholds are useful tools for assessing the potential for damage to facilities or multi-structure campuses based on input ground motions only. With as little as one strong-motion station per site, this scalable approach can provide rapid alarms on the damage status of remote towns, critical infrastructure (e.g., hospitals, schools) and points of interests (e.g., bridges) for a very large number of locations enabling better rapid decision making during critical and difficult immediate post-earthquake response actions. Details on the novel approach are presented along with an example implementation for a large energy company. Real-time calculation of PSA exceedance and alarm dissemination are enabled with Bighorn, an extension module based on the Antelope software package that combines real-time spectral monitoring and alarm capabilities with a robust built-in web display server. Antelope is an environmental data collection software package from Boulder Real Time Technologies (BRTT) typically used for very large seismic networks and real-time seismic data analyses. The primary processing engine produces continuous time-dependent response spectra for incoming acceleration streams. It utilizes expanded floating-point data representations within object ring-buffer packets and waveform files in a relational database. This leads to a very fast method for computing response spectra for a large number of channels. A Python script evaluates these response spectra for exceedance of one or more specified spectral limits, reporting any such exceedances via alarm packets that are put in the object ring-buffer for use by any alarm processes that need them. The web-display subsystem allows alert dissemination, interactive exploration, and alarm cancellation via the WWW.

On the strength of random fiber networks

NASA Astrophysics Data System (ADS)

Deogekar, S.; Picu, R. C.

2018-07-01

Damage accumulation and failure in random fiber networks is of importance in a variety of applications, from design of synthetic materials, such as paper and non-wovens, to accidental tearing of biological tissues. In this work we study these processes using three-dimensional models of athermal fiber networks, focusing attention on the modes of failure and on the relationship between network strength and network structural parameters. We consider network failure at small and large strains associated with the rupture of inter-fiber bonds. It is observed that the strength increases linearly with the network volume fraction and with the bond strength, while the stretch at peak stress is inversely related to these two parameters. A small fraction of the bonds rupture before peak stress and this fraction increases with increasing failure stretch. Rendering the bond strength stochastic causes a reduction of the network strength. However, heterogeneity retards damage localization and increases the stretch at peak stress, therefore promoting ductility.

Monitoring Damage Propagation in Glass Fiber Composites Using Carbon Nanofibers.

PubMed

Al-Sabagh, Ahmed; Taha, Eman; Kandil, Usama; Nasr, Gamal-Abdelnaser; Reda Taha, Mahmoud

2016-09-10

In this work, we report the potential use of novel carbon nanofibers (CNFs), dispersed during fabrication of glass fiber composites to monitor damage propagation under static loading. The use of CNFs enables a transformation of the typically non-conductive glass fiber composites into new fiber composites with appreciable electrical conductivity. The percolation limit of CNFs/epoxy nanocomposites was first quantified. The electromechanical responses of glass fiber composites fabricated using CNFs/epoxy nanocomposite were examined under static tension loads. The experimental observations showed a nonlinear change of electrical conductivity of glass fiber composites incorporating CNFs versus the stress level under static load. Microstructural investigations proved the ability of CNFs to alter the polymer matrix and to produce a new polymer nanocomposite with a connected nanofiber network with improved electrical properties and different mechanical properties compared with the neat epoxy. It is concluded that incorporating CNFs during fabrication of glass fiber composites can provide an innovative means of self-sensing that will allow damage propagation to be monitored in glass fiber composites.

Ultimate compression after impact load prediction in graphite/epoxy coupons using neural network and multivariate statistical analyses

NASA Astrophysics Data System (ADS)

Gregoire, Alexandre David

2011-07-01

The goal of this research was to accurately predict the ultimate compressive load of impact damaged graphite/epoxy coupons using a Kohonen self-organizing map (SOM) neural network and multivariate statistical regression analysis (MSRA). An optimized use of these data treatment tools allowed the generation of a simple, physically understandable equation that predicts the ultimate failure load of an impacted damaged coupon based uniquely on the acoustic emissions it emits at low proof loads. Acoustic emission (AE) data were collected using two 150 kHz resonant transducers which detected and recorded the AE activity given off during compression to failure of thirty-four impacted 24-ply bidirectional woven cloth laminate graphite/epoxy coupons. The AE quantification parameters duration, energy and amplitude for each AE hit were input to the Kohonen self-organizing map (SOM) neural network to accurately classify the material failure mechanisms present in the low proof load data. The number of failure mechanisms from the first 30% of the loading for twenty-four coupons were used to generate a linear prediction equation which yielded a worst case ultimate load prediction error of 16.17%, just outside of the +/-15% B-basis allowables, which was the goal for this research. Particular emphasis was placed upon the noise removal process which was largely responsible for the accuracy of the results.

Response of power systems to the San Fernando Valley earthquake of 9 February 1971. Final report

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

Schiff, A.J.; Yao, J.T.P.

1972-01-01

The impact of the San Fernando Valley earthquake on electric power systems is discussed. Particular attention focused on the following three areas; (1) the effects of an earthquake on the power network in the Western States, (2) the failure of subsystems and components of the power system, and (3) the loss of power to hospitals. The report includes sections on the description and functions of major components of a power network, existing procedures to protect the network, safety devices within the system which influence the network, a summary of the effects of the San Fernando Valley earthquake on the Westernmore » States Power Network, and present efforts to reduce the network vulnerability to faults. Also included in the report are a review of design procedures and practices prior to the San Fernando Valley earthquake and descriptions of types of damage to electrical equipment, dynamic analysis of equipment failures, equipment surviving the San Fernando Valley earthquake and new seismic design specifications. In addition, some observations and insights gained during the study, which are not directly related to power systems are discussed.« less

Patterns of recruitment and injury in a heterogeneous airway network model

PubMed Central

Stewart, Peter S.; Jensen, Oliver E.

2015-01-01

In respiratory distress, lung airways become flooded with liquid and may collapse due to surface-tension forces acting on air–liquid interfaces, inhibiting gas exchange. This paper proposes a mathematical multiscale model for the mechanical ventilation of a network of occluded airways, where air is forced into the network at a fixed tidal volume, allowing investigation of optimal recruitment strategies. The temporal response is derived from mechanistic models of individual airway reopening, incorporating feedback on the airway pressure due to recruitment. The model accounts for stochastic variability in airway diameter and stiffness across and between generations. For weak heterogeneity, the network is completely ventilated via one or more avalanches of recruitment (with airways recruited in quick succession), each characterized by a transient decrease in the airway pressure; avalanches become more erratic for airways that are initially more flooded. However, the time taken for complete ventilation of the network increases significantly as the network becomes more heterogeneous, leading to increased stresses on airway walls. The model predicts that the most peripheral airways are most at risk of ventilation-induced damage. A positive-end-expiratory pressure reduces the total recruitment time but at the cost of larger stresses exerted on airway walls. PMID:26423440

Acoustic emission based damage localization in composites structures using Bayesian identification

NASA Astrophysics Data System (ADS)

Kundu, A.; Eaton, M. J.; Al-Jumali, S.; Sikdar, S.; Pullin, R.

2017-05-01

Acoustic emission based damage detection in composite structures is based on detection of ultra high frequency packets of acoustic waves emitted from damage sources (such as fibre breakage, fatigue fracture, amongst others) with a network of distributed sensors. This non-destructive monitoring scheme requires solving an inverse problem where the measured signals are linked back to the location of the source. This in turn enables rapid deployment of mitigative measures. The presence of significant amount of uncertainty associated with the operating conditions and measurements makes the problem of damage identification quite challenging. The uncertainties stem from the fact that the measured signals are affected by the irregular geometries, manufacturing imprecision, imperfect boundary conditions, existing damages/structural degradation, amongst others. This work aims to tackle these uncertainties within a framework of automated probabilistic damage detection. The method trains a probabilistic model of the parametrized input and output model of the acoustic emission system with experimental data to give probabilistic descriptors of damage locations. A response surface modelling the acoustic emission as a function of parametrized damage signals collected from sensors would be calibrated with a training dataset using Bayesian inference. This is used to deduce damage locations in the online monitoring phase. During online monitoring, the spatially correlated time data is utilized in conjunction with the calibrated acoustic emissions model to infer the probabilistic description of the acoustic emission source within a hierarchical Bayesian inference framework. The methodology is tested on a composite structure consisting of carbon fibre panel with stiffeners and damage source behaviour has been experimentally simulated using standard H-N sources. The methodology presented in this study would be applicable in the current form to structural damage detection under varying operational loads and would be investigated in future studies.

Canceled connections: Lesion-derived network mapping helps explain differences in performance on a complex decision-making task

PubMed Central

Sutterer, Matthew J.; Bruss, Joel; Boes, Aaron D.; Voss, Michelle W.; Bechara, Antoine; Tranel, Daniel

2016-01-01

Studies of patients with brain damage have highlighted a broad neural network of limbic and prefrontal areas as important for adaptive decision-making. However, some patients with damage outside these regions have impaired decision-making behavior, and the behavioral impairments observed in these cases are often attributed to the general variability in behavior following brain damage, rather than a deficit in a specific brain-behavior relationship. A novel approach, lesion-derived network mapping, uses healthy subject resting-state functional connectivity (RSFC) data to infer the areas that would be connected with each patient’s lesion area in healthy adults. Here, we used this approach to investigate whether there was a systematic pattern of connectivity associated with decision-making performance in patients with focal damage in areas not classically associated with decision-making. These patients were categorized a priori into “impaired” or “unimpaired” groups based on their performance on the Iowa Gambling Task (IGT). Lesion-derived network maps based on the impaired patients showed overlap in somatosensory, motor and insula cortices, to a greater extent than patients who showed unimpaired IGT performance. Akin to the classic concept of “diaschisis” (von Monakow, 1914), this focus on the remote effects that focal damage can have on large-scale distributed brain networks has the potential to inform not only differences in decision-making behavior, but also other cognitive functions or neurological syndromes where a distinct phenotype has eluded neuroanatomical classification and brain-behavior relationships appear highly heterogeneous. PMID:26994344

Identification of evolutionarily conserved DNA damage response genes that alter sensitivity to cisplatin

PubMed Central

Gaponova, Anna V.; Deneka, Alexander Y.; Beck, Tim N.; Liu, Hanqing; Andrianov, Gregory; Nikonova, Anna S.; Nicolas, Emmanuelle; Einarson, Margret B.; Golemis, Erica A.; Serebriiskii, Ilya G.

2017-01-01

Ovarian, head and neck, and other cancers are commonly treated with cisplatin and other DNA damaging cytotoxic agents. Altered DNA damage response (DDR) contributes to resistance of these tumors to chemotherapies, some targeted therapies, and radiation. DDR involves multiple protein complexes and signaling pathways, some of which are evolutionarily ancient and involve protein orthologs conserved from yeast to humans. To identify new regulators of cisplatin-resistance in human tumors, we integrated high throughput and curated datasets describing yeast genes that regulate sensitivity to cisplatin and/or ionizing radiation. Next, we clustered highly validated genes based on chemogenomic profiling, and then mapped orthologs of these genes in expanded genomic networks for multiple metazoans, including humans. This approach identified an enriched candidate set of genes involved in the regulation of resistance to radiation and/or cisplatin in humans. Direct functional assessment of selected candidate genes using RNA interference confirmed their activity in influencing cisplatin resistance, degree of γH2AX focus formation and ATR phosphorylation, in ovarian and head and neck cancer cell lines, suggesting impaired DDR signaling as the driving mechanism. This work enlarges the set of genes that may contribute to chemotherapy resistance and provides a new contextual resource for interpreting next generation sequencing (NGS) genomic profiling of tumors. PMID:27863405

PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response

PubMed Central

Xie, Liang; Pi, Xinchun; Mishra, Ashutosh; Fong, Guohua; Peng, Junmin; Patterson, Cam

2012-01-01

The DNA damage response (DDR) is a complex regulatory network that is critical for maintaining genome integrity. Posttranslational modifications are widely used to ensure strict spatiotemporal control of signal flow, but how the DDR responds to environmental cues, such as changes in ambient oxygen tension, remains poorly understood. We found that an essential component of the ATR/CHK1 signaling pathway, the human homolog of the Caenorhabditis elegans biological clock protein CLK-2 (HCLK2), associated with and was hydroxylated by prolyl hydroxylase domain protein 3 (PHD3). HCLK2 hydroxylation was necessary for its interaction with ATR and the subsequent activation of ATR/CHK1/p53. Inhibiting PHD3, either with the pan-hydroxylase inhibitor dimethyloxaloylglycine (DMOG) or through hypoxia, prevented activation of the ATR/CHK1/p53 pathway and decreased apoptosis induced by DNA damage. Consistent with these observations, we found that mice lacking PHD3 were resistant to the effects of ionizing radiation and had decreased thymic apoptosis, a biomarker of genomic integrity. Our identification of HCLK2 as a substrate of PHD3 reveals the mechanism through which hypoxia inhibits the DDR, suggesting hydroxylation of HCLK2 is a potential therapeutic target for regulating the ATR/CHK1/p53 pathway. PMID:22797300

Thermal stability of electron-irradiated poly(tetrafluoroethylene) - X-ray photoelectron and mass spectroscopic study

NASA Technical Reports Server (NTRS)

Wheeler, Donald R.; Pepper, Stephen V.

1990-01-01

Polytetrafluoroethylene (PTFE) was subjected to 3 keV electron bombardment and then heated in vacuum to 300 C. The behavior of the material as a function of radiation dose and temperature was studied by X-ray photoelectron spectroscopy (XPS) of the surface and mass spectroscopy of the species evolved. Lightly damaged material heated to 300 C evolved saturated fluorocarbon species, whereas unsaturated fluorocarbon species were evolved from heavily damaged material. After heating the heavily damaged material, those features in the XPS spectrum that were associated with damage diminished, giving the appearance that the radiation damage had annealed. The observations were interpreted by incorporating mass transport of severed chain fragments and thermal decomposition of severely damaged material into the branched and cross-linked network model of irradiated PTFE. The apparent annealing of the radiation damage was due to covering of the network by saturated fragments that easily diffused through the decomposed material to the surface region upon heating.

Systematic analysis of nonlinear ground motion and temporal changes of material properties produced by small and medium earthquakes

NASA Astrophysics Data System (ADS)

Wu, C.; Peng, Z.; Ben-Zion, Y.

2009-12-01

Recent studies based on spectral ratio analysis have found clear temporal changes of material properties in the shallow crust and around active fault zones during large earthquakes with peak ground acceleration (PGA) larger than 100-200 gals (e.g., Sawazaki et al., GRL, 2006; Rubenstein et al., JGR, 2007; Wu et al., GJI, 2009). The temporal evolution of properties is generally characterized by a clear drop of resonant frequency and increased damping, followed by logarithmic recoveries with time. The shift in resonant frequency and damping are considered two hallmarks of nonlinear response associated with increasing material damage. However, an existing damage can produce similar changes in resonance curves with increasing wave amplitude, even in cases when the material damage does not increase (Lyakhovsky et al., GJI, 2009). In such cases the recovery of resonance properties with reduced source amplitude should be essentially instantaneous. It is important to distinguish with in situ seismic data nonlinear wave propagation effects that reflect fixed vs. evolving material damage. Here we systematically analyze temporal changes of material properties and nonlinear response associated with small and medium earthquakes, using seismic data recorded by the Japanese Strong Motion Network KIK-Net, a temporary 10-station PASSCAL seismic network along the North Anatolian Fault in Turkey, and the borehole and surface stations around the Parkfield section of the San Andreas fault. We compute the spectral ratios of windowed records from a pair of target and reference stations, and apply the sliding-window to the entire seismic records including the pre-event noise, P and S waves, and the early and late S-coda waves. We choose small and medium events to reduce the effects from additional material damage and use small sliding-window size to capture the subtle changes in the spectral ratios. The spectral ratio traces from windows within certain PGA ranges are then stacked to enhance the stability of the results. The preliminary results from the KIK-Net data suggest that the resonant frequency starts to decrease for PGA levels of several tens of gals, followed by near instantaneous recovery. Updated results from analysis of all the datasets will be presented in the meeting.

Plastic Surgery Response in Natural Disasters.

PubMed

Chung, Susan; Zimmerman, Amanda; Gaviria, Andres; Dayicioglu, Deniz

2015-06-01

Disasters cause untold damage and are often unpredictable; however, with proper preparation, these events can be better managed. The initial response has the greatest impact on the overall success of the relief effort. A well-trained multidisciplinary network of providers is necessary to ensure coordinated care for the victims of these mass casualty disasters. As members of this network of providers, plastic surgeons have the ability to efficiently address injuries sustained in mass casualty disasters and are a valuable member of the relief effort. The skill set of plastic surgeons includes techniques that can address injuries sustained in large-scale emergencies, such as the management of soft-tissue injury, tissue viability, facial fractures, and extremity salvage. An approach to disaster relief, the types of disasters encountered, the management of injuries related to mass casualty disasters, the role of plastic surgeons in the relief effort, and resource management are discussed. In order to improve preparedness in future mass casualty disasters, plastic surgeons should receive training during residency regarding the utilization of plastic surgery knowledge in the disaster setting.

Traumatic brain injury impairs small-world topology

PubMed Central

Pandit, Anand S.; Expert, Paul; Lambiotte, Renaud; Bonnelle, Valerie; Leech, Robert; Turkheimer, Federico E.

2013-01-01

Objective: We test the hypothesis that brain networks associated with cognitive function shift away from a “small-world” organization following traumatic brain injury (TBI). Methods: We investigated 20 TBI patients and 21 age-matched controls. Resting-state functional MRI was used to study functional connectivity. Graph theoretical analysis was then applied to partial correlation matrices derived from these data. The presence of white matter damage was quantified using diffusion tensor imaging. Results: Patients showed characteristic cognitive impairments as well as evidence of damage to white matter tracts. Compared to controls, the graph analysis showed reduced overall connectivity, longer average path lengths, and reduced network efficiency. A particular impact of TBI is seen on a major network hub, the posterior cingulate cortex. Taken together, these results confirm that a network critical to cognitive function shows a shift away from small-world characteristics. Conclusions: We provide evidence that key brain networks involved in supporting cognitive function become less small-world in their organization after TBI. This is likely to be the result of diffuse white matter damage, and may be an important factor in producing cognitive impairment after TBI. PMID:23596068

Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes.

PubMed

Calabrese, Vittorio; Cornelius, Carolin; Stella, Anna Maria Giuffrida; Calabrese, Edward J

2010-12-01

The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. A prediction of this theory is that, among species, differential rates of aging may be apparent on the basis of intrinsic differences in oxidative damage accrual. Although widely accepted, there is a growing number of exceptions to this theory, most contingently related to genetic model organism investigations. Proteins are one of the prime targets for oxidative damage and cysteine residues are particularly sensitive to reversible and irreversible oxidation. The adaptation and survival of cells and organisms requires the ability to sense proteotoxic insults and to coordinate protective cellular stress response pathways and chaperone networks related to protein quality control and stability. The toxic effects that stem from the misassembly or aggregation of proteins or peptides, in any cell type, are collectively termed proteotoxicity. Despite the abundance and apparent capacity of chaperones and other components of homeostasis to restore folding equilibrium, the cell appears poorly adapted for chronic proteotoxic stress which increases in cancer, metabolic and neurodegenerative diseases. Pharmacological modulation of cellular stress response pathways has emerging implications for the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. A critical key to successful medical intervention is getting the dose right. Achieving this goal can be extremely challenging due to human inter-individual variation as affected by age, gender, diet, exercise, genetic factors and health status. The nature of the dose response in and adjacent to the therapeutic zones, over the past decade has received considerable advances. The hormetic dose-response, challenging long-standing beliefs about the nature of the dose-response in a lowdose zone, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses, including carnitines. This paper describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including the possible signaling mechanisms by which the carnitine system, by interplaying metabolism, mitochondrial energetics and activation of critical vitagenes, modulates signal transduction cascades that confer cytoprotection against chronic degenerative damage associated to aging and neurodegenerative disorders.

Nested Neural Networks

NASA Technical Reports Server (NTRS)

Baram, Yoram

1992-01-01

Report presents analysis of nested neural networks, consisting of interconnected subnetworks. Analysis based on simplified mathematical models more appropriate for artificial electronic neural networks, partly applicable to biological neural networks. Nested structure allows for retrieval of individual subpatterns. Requires fewer wires and connection devices than fully connected networks, and allows for local reconstruction of damaged subnetworks without rewiring entire network.

The February 21, 1993 tornadoes of East Tennessee

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

Fricke, K.E.; Kornegay, F.C.

1993-08-11

A series of tornadoes struck the east Tennessee area on Sunday afternoon, February 21, 1993 around Knoxville, Lenoir City, and Oak Ridge causing millions of dollars worth of damage to both homes and businesses in the area, killing one, injuring a number of persons, and leaving a large area without power for many hours or even days due to damage to the local TVA transmission line network. One tornado touched down in the Department of Energy Oak Ridge Reservation near the Oak Ridge Y-12 Plant, continued through the Union Valley business district located just east of the plant, through themore » adjacent University of Tennessee Arboretum and then continued into the communities of Claxton and Powell. The path length of the tornado was approximately 13 miles. Damage to the Y-12 Plant was minimal, but the Union Valley business district was seriously damaged, including the Fusion Energy Design Center (FEDC) which houses a number of DOE related projects. The preliminary cost estimate of the damage to DOE facilities (both at Y-12 and at the FEDC) was around $520,000. This paper describes the local meteorological data, the tornado that struck near the Y-12 plant, the resulting damage both to the DOE facilities and to the surrounding communities, the plant emergency response and recovery activities, and the current hazard analyses being undertaken at the plant.« less

A Neural Network/Acoustic Emission Analysis of Impact Damaged Graphite/Epoxy Pressure Vessels

NASA Technical Reports Server (NTRS)

Walker, James L.; Hill, Erik v. K.; Workman, Gary L.; Russell, Samuel S.

1995-01-01

Acoustic emission (AE) signal analysis has been used to measure the effects of impact damage on burst pressure in 5.75 inch diameter, inert propellant filled, filament wound pressure vessels. The AE data were collected from fifteen graphite/epoxy pressure vessels featuring five damage states and three resin systems. A burst pressure prediction model was developed by correlating the AE amplitude (frequency) distribution, generated during the first pressure ramp to 800 psig (approximately 25% of the average expected burst pressure for an undamaged vessel) to known burst pressures using a four layered back propagation neural network. The neural network, trained on three vessels from each resin system, was able to predict burst pressures with a worst case error of 5.7% for the entire fifteen bottle set.

Self-Reporting Fiber-Reinforced Composites That Mimic the Ability of Biological Materials to Sense and Report Damage.

PubMed

Rifaie-Graham, Omar; Apebende, Edward A; Bast, Livia K; Bruns, Nico

2018-05-01

Sensing of damage, deformation, and mechanical forces is of vital importance in many applications of fiber-reinforced polymer composites, as it allows the structural health and integrity of composite components to be monitored and microdamage to be detected before it leads to catastrophic material failure. Bioinspired and biomimetic approaches to self-sensing and self-reporting materials are reviewed. Examples include bruising coatings and bleeding composites based on dye-filled microcapsules, hollow fibers, and vascular networks. Force-induced changes in color, fluorescence, or luminescence are achieved by mechanochromic epoxy resins, or by mechanophores and force-responsive proteins located at the interface of glass/carbon fibers and polymers. Composites can also feel strain, stress, and damage through embedded optical and electrical sensors, such as fiber Bragg grating sensors, or by resistance measurements of dispersed carbon fibers and carbon nanotubes. Bioinspired composites with the ability to show autonomously if and where they have been damaged lead to a multitude of opportunities for aerospace, automotive, civil engineering, and wind-turbine applications. They range from safety features for the detection of barely visible impact damage, to the real-time monitoring of deformation of load-bearing components. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative analysis of neural network and regression based condition monitoring approaches for wind turbine fault detection

NASA Astrophysics Data System (ADS)

Schlechtingen, Meik; Ferreira Santos, Ilmar

2011-07-01

This paper presents the research results of a comparison of three different model based approaches for wind turbine fault detection in online SCADA data, by applying developed models to five real measured faults and anomalies. The regression based model as the simplest approach to build a normal behavior model is compared to two artificial neural network based approaches, which are a full signal reconstruction and an autoregressive normal behavior model. Based on a real time series containing two generator bearing damages the capabilities of identifying the incipient fault prior to the actual failure are investigated. The period after the first bearing damage is used to develop the three normal behavior models. The developed or trained models are used to investigate how the second damage manifests in the prediction error. Furthermore the full signal reconstruction and the autoregressive approach are applied to further real time series containing gearbox bearing damages and stator temperature anomalies. The comparison revealed all three models being capable of detecting incipient faults. However, they differ in the effort required for model development and the remaining operational time after first indication of damage. The general nonlinear neural network approaches outperform the regression model. The remaining seasonality in the regression model prediction error makes it difficult to detect abnormality and leads to increased alarm levels and thus a shorter remaining operational period. For the bearing damages and the stator anomalies under investigation the full signal reconstruction neural network gave the best fault visibility and thus led to the highest confidence level.

Multisensory speech perception without the left superior temporal sulcus.

PubMed

Baum, Sarah H; Martin, Randi C; Hamilton, A Cris; Beauchamp, Michael S

2012-09-01

Converging evidence suggests that the left superior temporal sulcus (STS) is a critical site for multisensory integration of auditory and visual information during speech perception. We report a patient, SJ, who suffered a stroke that damaged the left tempo-parietal area, resulting in mild anomic aphasia. Structural MRI showed complete destruction of the left middle and posterior STS, as well as damage to adjacent areas in the temporal and parietal lobes. Surprisingly, SJ demonstrated preserved multisensory integration measured with two independent tests. First, she perceived the McGurk effect, an illusion that requires integration of auditory and visual speech. Second, her perception of morphed audiovisual speech with ambiguous auditory or visual information was significantly influenced by the opposing modality. To understand the neural basis for this preserved multisensory integration, blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine brain responses to audiovisual speech in SJ and 23 healthy age-matched controls. In controls, bilateral STS activity was observed. In SJ, no activity was observed in the damaged left STS but in the right STS, more cortex was active in SJ than in any of the normal controls. Further, the amplitude of the BOLD response in right STS response to McGurk stimuli was significantly greater in SJ than in controls. The simplest explanation of these results is a reorganization of SJ's cortical language networks such that the right STS now subserves multisensory integration of speech. Copyright © 2012 Elsevier Inc. All rights reserved.

Multisensory Speech Perception Without the Left Superior Temporal Sulcus

PubMed Central

Baum, Sarah H.; Martin, Randi C.; Hamilton, A. Cris; Beauchamp, Michael S.

2012-01-01

Converging evidence suggests that the left superior temporal sulcus (STS) is a critical site for multisensory integration of auditory and visual information during speech perception. We report a patient, SJ, who suffered a stroke that damaged the left tempo-parietal area, resulting in mild anomic aphasia. Structural MRI showed complete destruction of the left middle and posterior STS, as well as damage to adjacent areas in the temporal and parietal lobes. Surprisingly, SJ demonstrated preserved multisensory integration measured with two independent tests. First, she perceived the McGurk effect, an illusion that requires integration of auditory and visual speech. Second, her perception of morphed audiovisual speech with ambiguous auditory or visual information was significantly influenced by the opposing modality. To understand the neural basis for this preserved multisensory integration, blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine brain responses to audiovisual speech in SJ and 23 healthy age-matched controls. In controls, bilateral STS activity was observed. In SJ, no activity was observed in the damaged left STS but in the right STS, more cortex was active in SJ than in any of the normal controls. Further, the amplitude of the BOLD response in right STS response to McGurk stimuli was significantly greater in SJ than in controls. The simplest explanation of these results is a reorganization of SJ's cortical language networks such that the right STS now subserves multisensory integration of speech. PMID:22634292

C/EBPα expression is downregulated in human nonmelanoma skin cancers and inactivation of C/EBPα confers susceptibility to UVB-induced skin squamous cell carcinomas.

PubMed

Thompson, Elizabeth A; Zhu, Songyun; Hall, Jonathan R; House, John S; Ranjan, Rakesh; Burr, Jeanne A; He, Yu-Ying; Owens, David M; Smart, Robert C

2011-06-01

Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPα (CCAAT/enhancer-binding protein-α) in the DNA damage response network, where C/EBPα is induced following UVB DNA damage, regulates the G(1) checkpoint, and diminished or ablated expression of C/EBPα results in G(1) checkpoint failure. In the current study we observed that C/EBPα is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBPα expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPα similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPα. To determine the significance of C/EBPα in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPα (CKOα) were exposed to UVB. CKOα mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOα mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPα is silenced in human SCC and loss of C/EBPα confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB.

C/EBPα Expression Is Downregulated in Human Nonmelanoma Skin Cancers and Inactivation of C/EBPα Confers Susceptibility to UVB-Induced Skin Squamous Cell Carcinomas

PubMed Central

Thompson, Elizabeth A.; Zhu, Songyun; Hall, Jonathan R.; House, John S.; Ranjan, Rakesh; Burr, Jeanne A.; He, Yu-Ying; Owens, David M.; Smart, Robert C.

2012-01-01

Human epidermis is routinely subjected to DNA damage induced by UVB solar radiation. Cell culture studies have revealed an unexpected role for C/EBPα (CCAAT/enhancer-binding protein-α) in the DNA damage response network, where C/EBPα is induced following UVB DNA damage, regulates the G1 checkpoint, and diminished or ablated expression of C/EBPα results in G1 checkpoint failure. In the current study we observed that C/EBPα is induced in normal human epidermal keratinocytes and in the epidermis of human subjects exposed to UVB radiation. The analysis of human skin precancerous and cancerous lesions (47 cases) for C/EBPα expression was conducted. Actinic keratoses, a precancerous benign skin growth and precursor to squamous cell carcinoma (SCC), expressed levels of C/EBPα similar to normal epidermis. Strikingly, all invasive SCCs no longer expressed detectable levels of C/EBPα. To determine the significance of C/EBPα in UVB-induced skin cancer, SKH-1 mice lacking epidermal C/EBPα (CKOα) were exposed to UVB. CKOα mice were highly susceptible to UVB-induced SCCs and exhibited accelerated tumor progression. CKOα mice displayed keratinocyte cell cycle checkpoint failure in vivo in response to UVB that was characterized by abnormal entry of keratinocytes into S phase. Our results demonstrate that C/EBPα is silenced in human SCC and loss of C/EBPα confers susceptibility to UVB-induced skin SCCs involving defective cell cycle arrest in response to UVB. PMID:21346772

Rapid Response Products of The ARIA Project for the M6.0 August 24, 2014 South Napa Earthquake

NASA Astrophysics Data System (ADS)

Yun, S. H.; Owen, S. E.; Hua, H.; Milillo, P.; Fielding, E. J.; Hudnut, K. W.; Dawson, T. E.; Mccrink, T. P.; Jo, M. J.; Barnhart, W. D.; Manipon, G. J. M.; Agram, P. S.; Moore, A. W.; Jung, H. S.; Webb, F.; Milillo, G.; Rosinski, A.

2014-12-01

A magnitude 6.0 earthquake struck southern Napa county northeast of San Francisco, California, on Aug. 24, 2014, causing significant damage in the city of Napa and nearby areas. One day after the earthquake, the Advanced Rapid Imaging and Analysis (ARIA) team produced and released observations of coseismic ground displacement measured with continuous GPS stations of the Plate Boundary Observatory (operated by UNAVCO for the National Science Foundation) and the Bay Area Rapid Deformation network (operated by Berkeley Seismological Laboratory). Three days after the earthquake (Aug. 27), the Italian Space Agency's (ASI) COSMO-SkyMed (CSK) satellite acquired their first post-event data. On the same day, the ARIA team, in collaboration with ASI and University of Basilicata, produced and released a coseismic interferogram that revealed ground deformation and surface rupture. The depiction of the surface rupture - discontinuities of color fringes in the CSK interferogram - helped guide field geologists from the US Geological Survey and the California Geological Survey (CGS) to features that may have otherwise gone undetected. Small-scale cracks were found on a runway of the Napa County Airport, as well as bridge damage and damaged roads. ARIA's response to this event highlighted the importance of timeliness for mapping surface deformation features. ARIA's rapid response products were shared through Southern California Earthquake Center's response website and the California Earthquake Clearinghouse. A damage proxy map derived from InSAR coherence of CSK data was produced and distributed on Aug. 27. Field crews from the CGS identified true and false positives, including mobile home damage, newly planted grape vines, and a cripple wall failure of a house. Finite fault slip models constrained from CSK interferograms and continuous GPS observations reveal a north-propagating rupture with well-resolved slip from 0-10.5 km depth. We also measured along-track coseismic displacements of about -30 to 30 cm, along the main surface rupture, using multiple aperture interferometry and SAR pixel offset calculation. We also processed the European Space Agency's Sentinel-1A data on Sep. 3 and compared the result with the CSK interferogram, finding a general agreement between the two observations of surface deformation.

Acetaldehyde Stimulates FANCD2 Monoubiquitination, H2AX Phosphorylation, and BRCA1 Phosphorylation in Human Cells in Vitro: Implications for Alcohol-Related Carcinogenesis

PubMed Central

Marietta, Cheryl; Thompson, Larry H.; Lamerdin, Jane E.; Brooks, P.J.

2009-01-01

According to a recent IARC Working Group report, alcohol consumption is causally related to an increased risk of cancer of the upper aerodigestive tract, liver, colorectum, and female breast (Lancet Oncol. 2007 8:292–3). Several lines of evidence indicate that acetaldehyde (AA), the first product of alcohol metabolism, plays a very important role in alcohol-related carcinogenesis, particularly in the esophagus. We previously proposed a model for alcohol-related carcinogenesis in which AA, generated from alcohol metabolism, reacts in cells to generate DNA lesions that form interstrand crosslinks (ICLs) (Nucleic Acids Res. 2005 33:3513–20). Since the Fanconi anemia-breast cancer associated (FANC-BRCA) DNA damage response network plays a crucial role in protecting cells against ICLs, in the present work we tested this hypothesis by exposing cells to AA and monitoring activation of this network. We found that AA exposure results in a concentration-dependent increase in FANCD2 monoubiquitination, which is dependent upon the FANC core complex. AA also stimulated BRCA1 phosphorylation at Ser1524 and increased the level of γH2AX, with both modifications occurring in a dose-dependent manner. However, AA did not detectably increase the levels of hyperphosphorylated RPA34, a marker of single-stranded DNA exposure at replication forks. These results provide the initial description of the AA-DNA damage response, which is qualitatively similar to the cellular response to mitomycin C, a known DNA crosslinking agent. We discuss the mechanistic implications of these results, as well as their possible relationship to alcohol-related carcinogenesis in different human tissues. PMID:19428384

Non-destructive evaluation of laminated composite plates using dielectrometry sensors

NASA Astrophysics Data System (ADS)

Nassr, Amr A.; El-Dakhakhni, Wael W.

2009-05-01

The use of composite materials in marine, aerospace and automotive applications is increasing; however, several kinds of damages of composite materials may influence its durability and future applications. In this paper, a methodology was presented for damage detection of laminated composite plates using dielectrometry sensors. The presence of damage in the laminated composite plate leads to changes in its dielectric characteristics, causing variation in the measured capacitance by the sensors. An analytical model was used to analyse the influence of different sensor parameters on the output signals and to optimize sensor design. Two-dimensional finite element (FE) simulations were performed to assess the validity of the analytical results and to evaluate other sensor design-related parameters. To experimentally verify the model, the dielectric permittivity of the composite plate was measured. In addition, a glass fibre reinforced polymer (GFRP) laminated plate containing pre-fabricated slots through its thickness to simulate delamination and water intrusion defects was inspected in a laboratory setting. Excellent agreements were found between the experimental capacitance response signals and those predicated from the FE simulations. This cost-effective technique can be used for rapid damage screening, regular scheduled inspection, or as a permanent sensor network within the composite system.

Compensatory responses in plant-herbivore interactions: Impacts of insects on leaf water relations

NASA Astrophysics Data System (ADS)

Peschiutta, María L.; Bucci, Sandra J.; Scholz, Fabián G.; Goldstein, Guillermo

2016-05-01

Herbivore damage to leaves has been typically evaluated in terms of fractions of area removed; however morpho-physiological changes in the remaining tissues can occur in response to removal. We assessed the effects of partial removal of the leaf mesophyll by Caliroa cerasi (Hymenoptera) on leaf hydraulic conductance (Kleaf), vascular architecture, water relations and leaf size of three Prunus avium cultivars. The insect feeds on the leaf mesophyll leaving the vein network intact (skeletonization). Within each cultivar there were trees without infestations and trees chronically infested, at least over the last three years. Leaf size of intact leaves tended to be similar during leaf expansion before herbivore attack occurs across infested and non-infested trees. However, after herbivore attack and when the leaves were fully expanded, damaged leaves were smaller than leaves from non-infested trees. Damaged area varied between 21 and 31% depending on cultivar. The non-disruption of the vascular system together with either vein density or capacitance increased in damaged leaves resulted in similar Kleaf and stomatal conductance in infested and non-infested trees. Non-stomatal water loss from repeated leaf damage led to lower leaf water potentials in two of the infested cultivars. Lower leaf osmotic potentials and vulnerability to loss of Kleaf were observed in infested plants. Our results show that skeletonization resulted in compensatory changes in terms of water relations and hydraulics traits and in cultivar-specific physiological changes in phylogenetic related P. avium. Our findings indicate that detrimental effects of herbivory on the photosynthetic surface are counterbalanced by changes providing higher drought resistance, which has adaptive significance in ecosystems where water availability is low and furthermore where global climate changes would decrease soil water availability in the future even further.

Neural Network Prediction of Failure of Damaged Composite Pressure Vessels from Strain Field Data Acquired by a Computer Vision Method

NASA Technical Reports Server (NTRS)

Russell, Samuel S.; Lansing, Matthew D.

1997-01-01

This effort used a new and novel method of acquiring strains called Sub-pixel Digital Video Image Correlation (SDVIC) on impact damaged Kevlar/epoxy filament wound pressure vessels during a proof test. To predict the burst pressure, the hoop strain field distribution around the impact location from three vessels was used to train a neural network. The network was then tested on additional pressure vessels. Several variations on the network were tried. The best results were obtained using a single hidden layer. SDVIC is a fill-field non-contact computer vision technique which provides in-plane deformation and strain data over a load differential. This method was used to determine hoop and axial displacements, hoop and axial linear strains, the in-plane shear strains and rotations in the regions surrounding impact sites in filament wound pressure vessels (FWPV) during proof loading by internal pressurization. The relationship between these deformation measurement values and the remaining life of the pressure vessels, however, requires a complex theoretical model or numerical simulation. Both of these techniques are time consuming and complicated. Previous results using neural network methods had been successful in predicting the burst pressure for graphite/epoxy pressure vessels based upon acoustic emission (AE) measurements in similar tests. The neural network associates the character of the AE amplitude distribution, which depends upon the extent of impact damage, with the burst pressure. Similarly, higher amounts of impact damage are theorized to cause a higher amount of strain concentration in the damage effected zone at a given pressure and result in lower burst pressures. This relationship suggests that a neural network might be able to find an empirical relationship between the SDVIC strain field data and the burst pressure, analogous to the AE method, with greater speed and simplicity than theoretical or finite element modeling. The process of testing SDVIC neural network analysis and some encouraging preliminary results are presented in this paper. Details are given concerning the processing of SDVIC output data such that it may be used as back propagation neural network (BPNN) input data. The software written to perform this processing and the BPNN algorithm are also discussed. It will be shown that, with limited training, test results indicate an average error in burst pressure prediction of approximately six percent,

Salience network integrity predicts default mode network function after traumatic brain injury

PubMed Central

Bonnelle, Valerie; Ham, Timothy E.; Leech, Robert; Kinnunen, Kirsi M.; Mehta, Mitul A.; Greenwood, Richard J.; Sharp, David J.

2012-01-01

Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)—which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae—regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control. PMID:22393019

DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis.

PubMed

Enriquez-Rios, Vanessa; Dumitrache, Lavinia C; Downing, Susanna M; Li, Yang; Brown, Eric J; Russell, Helen R; McKinnon, Peter J

2017-01-25

The DNA damage response (DDR) orchestrates a network of cellular processes that integrates cell-cycle control and DNA repair or apoptosis, which serves to maintain genome stability. DNA-PKcs (the catalytic subunit of the DNA-dependent kinase, encoded by PRKDC), ATM (ataxia telangiectasia, mutated), and ATR (ATM and Rad3-related) are related PI3K-like protein kinases and central regulators of the DDR. Defects in these kinases have been linked to neurodegenerative or neurodevelopmental syndromes. In all cases, the key neuroprotective function of these kinases is uncertain. It also remains unclear how interactions between the three DNA damage-responsive kinases coordinate genome stability, particularly in a physiological context. Here, we used a genetic approach to identify the neural function of DNA-PKcs and the interplay between ATM and ATR during neurogenesis. We found that DNA-PKcs loss in the mouse sensitized neuronal progenitors to apoptosis after ionizing radiation because of excessive DNA damage. DNA-PKcs was also required to prevent endogenous DNA damage accumulation throughout the adult brain. In contrast, ATR coordinated the DDR during neurogenesis to direct apoptosis in cycling neural progenitors, whereas ATM regulated apoptosis in both proliferative and noncycling cells. We also found that ATR controls a DNA damage-induced G 2 /M checkpoint in cortical progenitors, independent of ATM and DNA-PKcs. These nonoverlapping roles were further confirmed via sustained murine embryonic or cortical development after all three kinases were simultaneously inactivated. Thus, our results illustrate how DNA-PKcs, ATM, and ATR have unique and essential roles during the DDR, collectively ensuring comprehensive genome maintenance in the nervous system. The DNA damage response (DDR) is essential for prevention of a broad spectrum of different human neurologic diseases. However, a detailed understanding of the DDR at a physiological level is lacking. In contrast to many in vitro cellular studies, here we demonstrate independent biological roles for the DDR kinases DNA-PKcs, ATM, and ATR during neurogenesis. We show that DNA-PKcs is central to DNA repair in nonproliferating cells, and restricts DNA damage accumulation, whereas ATR controls damage-induced G 2 checkpoint control and apoptosis in proliferating cells. Conversely, ATM is critical for controlling apoptosis in immature noncycling neural cells after DNA damage. These data demonstrate functionally distinct, but cooperative, roles for each kinase in preserving genome stability in the nervous system. Copyright © 2017 the authors 0270-6474/17/370893-13$15.00/0.

75 FR 26180 - Effects on Broadband Communications Networks of Damage To or Failure of Network Equipment or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

... seeks comment on the scope of its ancillary authority with regard to the matters described in this NOI... networks. For example, to what extent are core and edge network links protected with ``dark'' backup links...

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response.

PubMed

Luo, Man; Bao, Zhengqiang; Xu, Feng; Wang, Xiaohui; Li, Fei; Li, Wen; Chen, Zhihua; Ying, Songmin; Shen, Huahao

2018-04-14

The inflammatory cascade can be initiated with the recognition of damaged DNA. Macrophages play an essential role in particulate matter (PM)-induced airway inflammation. In this study, we aim to explore the PM induced DNA damage response of macrophages and its function in airway inflammation. The DNA damage response and inflammatory response were assessed using bone marrow-derived macrophages following PM treatment and mouse model instilled intratracheally with PM. We found that PM induced significant DNA damage both in vitro and in vivo and simultaneously triggered a rapid DNA damage response, represented by nuclear RPA, 53BP1 and γH2AX foci formation. Genetic ablation or chemical inhibition of the DNA damage response sensor amplified the production of cytokines including Cxcl1, Cxcl2 and Ifn-γ after PM stimulation in bone marrow-derived macrophages. Similar to that seen in vitro , mice with myeloid-specific deletion of RAD50 showed higher levels of airway inflammation in response to the PM challenge, suggesting a protective role of DNA damage sensor during inflammation. These data demonstrate that PM exposure induces DNA damage and activation of DNA damage response sensor MRN complex in macrophages. Disruption of MRN complex lead to persistent, unrepaired DNA damage that causes elevated inflammatory response.

SOS, the formidable strategy of bacteria against aggressions.

PubMed

Baharoglu, Zeynep; Mazel, Didier

2014-11-01

The presence of an abnormal amount of single-stranded DNA in the bacterial cell constitutes a genotoxic alarm signal that induces the SOS response, a broad regulatory network found in most bacterial species to address DNA damage. The aim of this review was to point out that beyond being a repair process, SOS induction leads to a very strong but transient response to genotoxic stress, during which bacteria can rearrange and mutate their genome, induce several phenotypic changes through differential regulation of genes, and sometimes acquire characteristics that potentiate bacterial survival and adaptation to changing environments. We review here the causes and consequences of SOS induction, but also how this response can be modulated under various circumstances and how it is connected to the network of other important stress responses. In the first section, we review articles describing the induction of the SOS response at the molecular level. The second section discusses consequences of this induction in terms of DNA repair, changes in the genome and gene expression, and sharing of genomic information, with their effects on the bacteria's life and evolution. The third section is about the fine tuning of this response to fit with the bacteria's 'needs'. Finally, we discuss recent findings linking the SOS response to other stress responses. Under these perspectives, SOS can be perceived as a powerful bacterial strategy against aggressions. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

17β-Estradiol Alters Oxidative Stress Response Protein Expression and Oxidative Damage in the Uterus

PubMed Central

Yuan, Lisi; Dietrich, Alicia K.; Nardulli, Ann M.

2014-01-01

The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels.Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis. PMID:24103313

Real-time vibration-based structural damage detection using one-dimensional convolutional neural networks

NASA Astrophysics Data System (ADS)

Abdeljaber, Osama; Avci, Onur; Kiranyaz, Serkan; Gabbouj, Moncef; Inman, Daniel J.

2017-02-01

Structural health monitoring (SHM) and vibration-based structural damage detection have been a continuous interest for civil, mechanical and aerospace engineers over the decades. Early and meticulous damage detection has always been one of the principal objectives of SHM applications. The performance of a classical damage detection system predominantly depends on the choice of the features and the classifier. While the fixed and hand-crafted features may either be a sub-optimal choice for a particular structure or fail to achieve the same level of performance on another structure, they usually require a large computation power which may hinder their usage for real-time structural damage detection. This paper presents a novel, fast and accurate structural damage detection system using 1D Convolutional Neural Networks (CNNs) that has an inherent adaptive design to fuse both feature extraction and classification blocks into a single and compact learning body. The proposed method performs vibration-based damage detection and localization of the damage in real-time. The advantage of this approach is its ability to extract optimal damage-sensitive features automatically from the raw acceleration signals. Large-scale experiments conducted on a grandstand simulator revealed an outstanding performance and verified the computational efficiency of the proposed real-time damage detection method.

Multiple tipping points and optimal repairing in interacting networks

PubMed Central

Majdandzic, Antonio; Braunstein, Lidia A.; Curme, Chester; Vodenska, Irena; Levy-Carciente, Sary; Eugene Stanley, H.; Havlin, Shlomo

2016-01-01

Systems composed of many interacting dynamical networks—such as the human body with its biological networks or the global economic network consisting of regional clusters—often exhibit complicated collective dynamics. Three fundamental processes that are typically present are failure, damage spread and recovery. Here we develop a model for such systems and find a very rich phase diagram that becomes increasingly more complex as the number of interacting networks increases. In the simplest example of two interacting networks we find two critical points, four triple points, ten allowed transitions and two ‘forbidden' transitions, as well as complex hysteresis loops. Remarkably, we find that triple points play the dominant role in constructing the optimal repairing strategy in damaged interacting systems. To test our model, we analyse an example of real interacting financial networks and find evidence of rapid dynamical transitions between well-defined states, in agreement with the predictions of our model. PMID:26926803

Mapping connectivity damage in the case of Phineas Gage.

PubMed

Van Horn, John Darrell; Irimia, Andrei; Torgerson, Carinna M; Chambers, Micah C; Kikinis, Ron; Toga, Arthur W

2012-01-01

White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a "tamping iron" was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25-36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized "average" brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient.

Geohazards on the Moon and the Importance of the International Lunar Network

NASA Technical Reports Server (NTRS)

Cohen, Barbara A.

2009-01-01

Seven of the 28 shallow seismic events recorded by the Apollo passive seismic experiment (PSE) network released energy equivalent to earthquakes with magnitudes of 5 or greater. On Earth, such quakes can cause extensive damage to structures near the epicenter. Unexpected structural damage to a lunar habitat could have devastating results and thus, lunar seismicity may present a significant geohazard to long-term human habitation.

The canonical semantic network supports residual language function in chronic post-stroke aphasia

PubMed Central

Griffis, Joseph C.; Nenert, Rodolphe; Allendorfer, Jane B.; Vannest, Jennifer; Holland, Scott; Dietz, Aimee; Szaflarski, Jerzy P.

2016-01-01

Current theories of language recovery after stroke are limited by a reliance on small studies. Here, we aimed to test predictions of current theory and resolve inconsistencies regarding right hemispheric contributions to long-term recovery. We first defined the canonical semantic network in 43 healthy controls. Then, in a group of 43 patients with chronic post-stroke aphasia, we tested whether activity in this network predicted performance on measures of semantic comprehension, naming, and fluency while controlling for lesion volume effects. Canonical network activation accounted for 22–33% of the variance in language test scores. Whole-brain analyses corroborated these findings, and revealed a core set of regions showing positive relationships to all language measures. We next evaluated the relationship between activation magnitudes in left and right hemispheric portions of the network, and characterized how right hemispheric activation related to the extent of left hemispheric damage. Activation magnitudes in each hemispheric network were strongly correlated, but four right frontal regions showed heightened activity in patients with large lesions. Activity in two of these regions (inferior frontal gyrus pars opercularis and supplementary motor area) was associated with better language abilities in patients with larger lesions, but poorer language abilities in patients with smaller lesions. Our results indicate that bilateral language networks support language processing after stroke, and that right hemispheric activations related to extensive left hemisphere damage occur outside of the canonical semantic network and differentially relate to behavior depending on the extent of left hemispheric damage. PMID:27981674

The Basal Ganglia and Adaptive Motor Control

NASA Astrophysics Data System (ADS)

Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

1994-09-01

The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

Impact papers on aging in 2009

PubMed Central

Blagosklonny, Mikhail V.; Campisi, Judy; Sinclair, David A.; Bartke, Andrzej; Blasco, Maria A.; Bonner, William M.; Bohr, Vilhelm A.; Jr, Robert M. Brosh; Brunet, Anne; DePinho, Ronald A.; Donehower, Lawrence A.; Finch, Caleb E.; Finkel, Toren; Gorospe, Myriam; Gudkov, Andrei V.; Hall, Michael N.; Hekimi, Siegfried; Helfand, Stephen L.; Karlseder, Jan; Kenyon, Cynthia; Kroemer, Guido; Longo, Valter; Nussenzweig, Andre; Osiewacz, Heinz D.; Peeper, Daniel S.; Rando, Thomas A.; Rudolph, K Lenhard; Sassone-Corsi, Paolo; Serrano, Manuel; Sharpless, Norman E.; Skulachev, Vladimir P.; Tilly, Jonathan L.; Tower, John; Verdin, Eric; Vijg, Jan

2010-01-01

The editorial board of Aging reviews research papers published in 2009, which they believe have or will have a significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacologic interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically. PMID:20351400

Novelty detection applied to vibration data from a CX-100 wind turbine blade under fatigue loading

NASA Astrophysics Data System (ADS)

Dervilis, N.; Choi, M.; Antoniadou, I.; Farinholt, K. M.; Taylor, S. G.; Barthorpe, R. J.; Park, G.; Worden, K.; Farrar, C. R.

2012-08-01

The remarkable evolution of new generation wind turbines has led to a dramatic increase of wind turbine blade size. In turn, a reliable structural health monitoring (SHM) system will be a key factor for the successful implementation of such systems. Detection of damage at an early stage is a crucial issue as blade failure would be a catastrophic result for the entire wind turbine. In this study the SHM analysis will be based on experimental measurements of Frequency Response Functions (FRFs) extracted by using an input/output acquisition technique under a fatigue loading of a 9m CX-100 blade at the National Renewable Energy Laboratory (NREL) and National Wind Technology Center (NWTC) performed in the Los Alamos National Laboratory. The blade was harmonically excited at its first natural frequency using a Universal Resonant Excitation (UREX) system. For analysis, the Auto-Associative Neural Network (AANN) is a non-parametric method where a set of damage sensitive features gathered from the measured structure are used to train a network that acts as a novelty detector. This traditionally has a highly complex "bottleneck" structure with five layers in the AANN. In the current paper, a new attempt is also exploited based on an AANN with one hidden layer in order to reduce the theoretical and computational difficulties. Damage detection of composite bodies of blades is a "grand challenge" due to varying aerodynamic and gravitational loads and environmental conditions. A study of the noise tolerant capability of the AANN which is associated to its generalisation capacity is addressed. It will be shown that vibration response data combined with AANNs is a robust and powerful tool, offering novelty detection even when operational and environmental variations are present. The AANN is a method which has not yet been widely used in the structural health monitoring of composite blades.

A Simplified Algorithm for Statistical Investigation of Damage Spreading

NASA Astrophysics Data System (ADS)

Gecow, Andrzej

2009-04-01

On the way to simulating adaptive evolution of complex system describing a living object or human developed project, a fitness should be defined on node states or network external outputs. Feedbacks lead to circular attractors of these states or outputs which make it difficult to define a fitness. The main statistical effects of adaptive condition are the result of small change tendency and to appear, they only need a statistically correct size of damage initiated by evolutionary change of system. This observation allows to cut loops of feedbacks and in effect to obtain a particular statistically correct state instead of a long circular attractor which in the quenched model is expected for chaotic network with feedback. Defining fitness on such states is simple. We calculate only damaged nodes and only once. Such an algorithm is optimal for investigation of damage spreading i.e. statistical connections of structural parameters of initial change with the size of effected damage. It is a reversed-annealed method—function and states (signals) may be randomly substituted but connections are important and are preserved. The small damages important for adaptive evolution are correctly depicted in comparison to Derrida annealed approximation which expects equilibrium levels for large networks. The algorithm indicates these levels correctly. The relevant program in Pascal, which executes the algorithm for a wide range of parameters, can be obtained from the author.

Computational modelling of the cerebral cortical microvasculature: effect of x-ray microbeams versus broad beam irradiation

NASA Astrophysics Data System (ADS)

Merrem, A.; Bartzsch, S.; Laissue, J.; Oelfke, U.

2017-05-01

Microbeam Radiation Therapy is an innovative pre-clinical strategy which uses arrays of parallel, tens of micrometres wide kilo-voltage photon beams to treat tumours. These x-ray beams are typically generated on a synchrotron source. It was shown that these beam geometries allow exceptional normal tissue sparing from radiation damage while still being effective in tumour ablation. A final biological explanation for this enhanced therapeutic ratio has still not been found, some experimental data support an important role of the vasculature. In this work, the effect of microbeams on a normal microvascular network of the cerebral cortex was assessed in computer simulations and compared to the effect of homogeneous, seamless exposures at equal energy absorption. The anatomy of a cerebral microvascular network and the inflicted radiation damage were simulated to closely mimic experimental data using a novel probabilistic model of radiation damage to blood vessels. It was found that the spatial dose fractionation by microbeam arrays significantly decreased the vascular damage. The higher the peak-to-valley dose ratio, the more pronounced the sparing effect. Simulations of the radiation damage as a function of morphological parameters of the vascular network demonstrated that the distribution of blood vessel radii is a key parameter determining both the overall radiation damage of the vasculature and the dose-dependent differential effect of microbeam irradiation.

Chromium genotoxicity: a double-edged sword

PubMed Central

Nickens, Kristen P.; Patierno, Steven R.; Ceryak, Susan

2010-01-01

Certain forms of hexavalent chromium [Cr(VI)] are known respiratory carcinogens that induce a broad spectrum of DNA damage. Cr(VI)-carcinogenesis may be initiated or promoted through several mechanistic processes including, the intracellular metabolic reduction of Cr(VI) producing chromium species capable of interacting with DNA to yield genotoxic and mutagenic effects, Cr(VI)-induced inflammatory/immunological responses, and alteration of survival signaling pathways. Cr(VI) enters the cell through nonspecific anion channels, and is metabolically reduced by agents including ascorbate, glutathione, and cysteine to Cr(V), Cr(IV), and Cr(III). Cr(III) has a weak membrane permeability capacity and is unable to cross the cell membrane, thereby trapping it within the cell where it can bind to DNA and produce genetic damage leading to genomic instability. Structural genetic lesions produced by the intracellular reduction of Cr(VI) include DNA adducts, DNA strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites, and DNA inter- and intrastrand crosslinks. The damage induced by Cr(VI) can lead to dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints, dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and the disruption of key regulatory gene networks responsible for the balance of cell survival and cell death, which may all play an important role in Cr(VI) carcinogenesis. Several lines of evidence have indicated that neoplastic progression is a result of consecutive genetic/epigenetic changes that provide cellular survival advantages, and ultimately lead to the conversion of normal human cells to malignant cancer cells. This review is based on studies that provide a glimpse into Cr(VI) carcinogenicity via mechanisms including Cr(VI)-induced death-resistance, the involvement of DNA repair mechanisms in survival after chromium exposure, and the activation of survival signaling cascades in response to Cr(VI) genotoxicity. PMID:20430016

Incidence of insects, diseases, and other damaging agents in Oregon forests.

Treesearch

Paul A. Dunham

2008-01-01

This report uses data from a network of forest inventory plots sampled at two points in time, annual aerial insect and disease surveys, and specialized pest damage surveys to quantify the incidence and impact of insects, diseases, and other damaging agents on Oregon's forests. The number and volume of trees damaged or killed by various agents is summarized....

Data driven innovations in structural health monitoring

NASA Astrophysics Data System (ADS)

Rosales, M. J.; Liyanapathirana, R.

2017-05-01

At present, substantial investments are being allocated to civil infrastructures also considered as valuable assets at a national or global scale. Structural Health Monitoring (SHM) is an indispensable tool required to ensure the performance and safety of these structures based on measured response parameters. The research to date on damage assessment has tended to focus on the utilization of wireless sensor networks (WSN) as it proves to be the best alternative over the traditional visual inspections and tethered or wired counterparts. Over the last decade, the structural health and behaviour of innumerable infrastructure has been measured and evaluated owing to several successful ventures of implementing these sensor networks. Various monitoring systems have the capability to rapidly transmit, measure, and store large capacities of data. The amount of data collected from these networks have eventually been unmanageable which paved the way to other relevant issues such as data quality, relevance, re-use, and decision support. There is an increasing need to integrate new technologies in order to automate the evaluation processes as well as to enhance the objectivity of data assessment routines. This paper aims to identify feasible methodologies towards the application of time-series analysis techniques to judiciously exploit the vast amount of readily available as well as the upcoming data resources. It continues the momentum of a greater effort to collect and archive SHM approaches that will serve as data-driven innovations for the assessment of damage through efficient algorithms and data analytics.

Assessment of liquefaction-induced hazards using Bayesian networks based on standard penetration test data

NASA Astrophysics Data System (ADS)

Tang, Xiao-Wei; Bai, Xu; Hu, Ji-Lei; Qiu, Jiang-Nan

2018-05-01

Liquefaction-induced hazards such as sand boils, ground cracks, settlement, and lateral spreading are responsible for considerable damage to engineering structures during major earthquakes. Presently, there is no effective empirical approach that can assess different liquefaction-induced hazards in one model. This is because of the uncertainties and complexity of the factors related to seismic liquefaction and liquefaction-induced hazards. In this study, Bayesian networks (BNs) are used to integrate multiple factors related to seismic liquefaction, sand boils, ground cracks, settlement, and lateral spreading into a model based on standard penetration test data. The constructed BN model can assess four different liquefaction-induced hazards together. In a case study, the BN method outperforms an artificial neural network and Ishihara and Yoshimine's simplified method in terms of accuracy, Brier score, recall, precision, and area under the curve (AUC) of the receiver operating characteristic (ROC). This demonstrates that the BN method is a good alternative tool for the risk assessment of liquefaction-induced hazards. Furthermore, the performance of the BN model in estimating liquefaction-induced hazards in Japan's 2011 Tōhoku earthquake confirms its correctness and reliability compared with the liquefaction potential index approach. The proposed BN model can also predict whether the soil becomes liquefied after an earthquake and can deduce the chain reaction process of liquefaction-induced hazards and perform backward reasoning. The assessment results from the proposed model provide informative guidelines for decision-makers to detect the damage state of a field following liquefaction.

76 FR 23812 - Reliability and Continuity of Communications Networks, Including Broadband Technologies; Effects...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-28

... FEDERAL COMMUNICATIONS COMMISSION [PS Docket Nos. 11-60 and 10-92; ET Docket No. 06-119] Reliability and Continuity of Communications Networks, Including Broadband Technologies; Effects on Broadband Communications Networks of Damage or Failure of Network Equipment or Severe Overload; Independent Panel Reviewing...

Damage spreading and opinion dynamics on scale-free networks

NASA Astrophysics Data System (ADS)

Fortunato, Santo

2005-03-01

We study damage spreading among the opinions of a system of agents, subjected to the dynamics of the Krause-Hegselmann consensus model. The damage consists in a sharp change of the opinion of one or more agents in the initial random opinion configuration, supposedly due to some external factors and/or events. This may help to understand for instance under which conditions special shocking events or targeted propaganda are able to influence the results of elections. For agents lying on the nodes of a Barabási-Albert network, there is a damage spreading transition at a low value εd of the confidence bound parameter. Interestingly, we find as well that there is some critical value εs above which the initial perturbation manages to propagate to all other agents.

Measurement of traffic network vulnerability for Mississippi coastal region : final research report.

DOT National Transportation Integrated Search

2017-08-15

Natural disasters such as a hurricane can cause great damages to the transportation networks and significantly affect the evacuation trip operations. An accurate understanding and measurement of the network vulnerability can enhance the evacuees p...

Possible role of interference, protein noise, and sink effects in nonphotochemical quenching in photosynthetic complexes.

PubMed

Berman, Gennady P; Nesterov, Alexander I; Gurvitz, Shmuel; Sayre, Richard T

2017-01-01

We analyze theoretically a simple and consistent quantum mechanical model that reveals the possible role of quantum interference, protein noise, and sink effects in the nonphotochemical quenching (NPQ) in light-harvesting complexes (LHCs). The model consists of a network of five interconnected sites (excitonic states of light-sensitive molecules) responsible for the NPQ mechanism. The model also includes the "damaging" and the dissipative channels. The damaging channel is responsible for production of singlet oxygen and other destructive outcomes. In our model, both damaging and "dissipative" charge transfer channels are described by discrete electron energy levels attached to their sinks, that mimic the continuum part of electron energy spectrum. All five excitonic sites interact with the protein environment that is modeled using a stochastic process. Our approach allowed us to derive the exact and closed system of linear ordinary differential equations for the reduced density matrix and its first momentums. These equations are solved numerically including for strong interactions between the light-sensitive molecules and protein environment. As an example, we apply our model to demonstrate possible contributions of quantum interference, protein noise, and sink effects in the NPQ mechanism in the CP29 minor LHC. The numerical simulations show that using proper combination of quantum interference effects, properties of noise, and sinks, one can significantly suppress the damaging channel. Our findings demonstrate the possible role of interference, protein noise, and sink effects for modeling, engineering, and optimizing the performance of the NPQ processes in both natural and artificial light-harvesting complexes.

Global Seismic Monitoring: Past, Present, and Future

NASA Astrophysics Data System (ADS)

Zoback, M.; Benz, H.; Oppenheimer, D.

2007-12-01

Global seismological observations began in April 1889 when an earthquake in Tokyo, Japan was accurately recorded in Germany on two different horizontal pendulum instruments. However, modern global observational seismology really began 46 years ago when the 120-station World Wide Standard Seismograph Network was installed by the US to monitor underground nuclear tests and earthquakes using well-calibrated short- and long- period stations. At the same time rapid advances in computing technology enabled researchers to begin sophisticated analysis of the increasing amount of seismic data, which led to better understanding of earthquake source properties and their use in establishing plate tectonics. Today, global seismic networks are operated by German (Geophon), France (Geoscope), the United States (Global Seismograph Network) and the International Monitoring System. Presently, the Federation of Digital Seismograph Networks registers more than 1,000 broadband stations world-wide, a small percentage of the total number of digital seismic stations around the world. Following the devastating Kobe, Japan and Northridge, California earthquakes, Japan and the US have led the world in the integration of existing seismic sensor systems (weak and strong motion) into development of near-real-time, post-earthquake response products like ShakeMap, detailing the spatial distribution of strong shaking. Future challenges include expanding real-time integration of both seismic and geodetic sensor systems to produce early warning of strong shaking, rapid source determination, as well as near-realtime post- earthquake damage assessment. Seismic network data, hydro-acoustic arrays, deep water tide gauges, and satellite imagery of wave propagation should be integrated in real-time to provide input for hydrodynamic modeling yielding the distribution, timing and size of tsunamis runup--which would then be available instantly on the web, e.g. in a Google Earth format. Dense arrays of strong motion sensors together with deployment of MEMS-type accelerometers in buildings and equipment routinely connected to the Web could potentially provide thousands of measurements of damaging strong ground motion. This technology could ultimately become part of smart building design enabling critical facilities to change their structural response to imminent strong shaking. Looking further forward, it is likely that a continuously observing spaceborne system could image the occurrence of "silent" or "slow" earthquakes as well as the propagation of ground displacement by surface waves at scales of continents.

Classifying transcription factor targets and discovering relevant biological features

PubMed Central

Holloway, Dustin T; Kon, Mark; DeLisi, Charles

2008-01-01

Background An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs) and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties. Principal Findings (1) Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4), Ino2(2.6), Yaf1(2.4), and Yap6(2.4). (2) Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression. (3) A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties. (4) An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and growth related regulators dominate the former; genes involved in carbon metabolism and energy generation dominate the latter. Conclusion Postprocessing of regulatory-classifier results can provide high quality predictions, and feature ranking strategies can deliver insight into the regulatory functions of TFs. Predictions are available at an online web-server, including the full transcriptional network, which can be analyzed using VisAnt network analysis suite. Reviewers This article was reviewed by Igor Jouline, Todd Mockler(nominated by Valerian Dolja), and Sandor Pongor. PMID:18513408

A new SMART sensing system for aerospace structures

NASA Astrophysics Data System (ADS)

Zhang, David C.; Yu, Pin; Beard, Shawn; Qing, Peter; Kumar, Amrita; Chang, Fu-Kuo

2007-04-01

It is essential to ensure the safety and reliability of in-service structures such as unmanned vehicles by detecting structural cracking, corrosion, delamination, material degradation and other types of damage in time. Utilization of an integrated sensor network system can enable automatic inspection of such damages ultimately. Using a built-in network of actuators and sensors, Acellent is providing tools for advanced structural diagnostics. Acellent's integrated structural health monitoring system consists of an actuator/sensor network, supporting signal generation and data acquisition hardware, and data processing, visualization and analysis software. This paper describes the various features of Acellent's latest SMART sensing system. The new system is USB-based and is ultra-portable using the state-of-the-art technology, while delivering many functions such as system self-diagnosis, sensor diagnosis, through-transmission mode and pulse-echo mode of operation and temperature measurement. Performance of the new system was evaluated for assessment of damage in composite structures.

A Shape Memory Alloy-Based Miniaturized Actuator for Catheter Interventions.

PubMed

Lu, Yueh-Hsun; Mani, Karthick; Panigrahi, Bivas; Hajari, Saurabh; Chen, Chia-Yuan

2018-06-26

In the current scenario of endovascular intervention, surgeons have to manually navigate the catheter within the complex vasculature of the human body under the guidance of X-ray. This manual intervention upsurges the possibilities of vessel damage due to frequent contact between the catheter and vasculature wall. In this context, a shape memory alloy-based miniaturized actuator was proposed in this study with a specific aim to reduce vessel wall related damage by improving the bending motions of the guidewire tip in a semi-automatic fashion. The miniaturized actuator was integrated with a FDA-approved guidewire and tested within a patient-specific vascular network model to realize its feasibility in the real surgical environment. The results illustrate that the miniaturized actuator gives a bending angle over 23° and lateral displacement over 900 µm to the guide wire tip by which the guidewire can be navigated with precision and possible vessel damage during the catheter intervention can certainly be minimized. In addition to it, the dynamic responses of the presented actuator were further investigated through numerical simulation in conjunction with the analytic analysis.

Longitudinal Dynamics of 3-Dimensional Components of Selfhood After Severe Traumatic Brain Injury: A qEEG Case Study.

PubMed

Fingelkurts, Andrew A; Fingelkurts, Alexander A

2017-09-01

In this report, we describe the case of a patient who sustained extremely severe traumatic brain damage with diffuse axonal injury in a traffic accident and whose recovery was monitored during 6 years. Specifically, we were interested in the recovery dynamics of 3-dimensional components of selfhood (a 3-dimensional construct model for the complex experiential selfhood has been recently proposed based on the empirical findings on the functional-topographical specialization of 3 operational modules of brain functional network responsible for the self-consciousness processing) derived from the electroencephalographic (EEG) signal. The analysis revealed progressive (though not monotonous) restoration of EEG functional connectivity of 3 modules of brain functional network responsible for the self-consciousness processing, which was also paralleled by the clinically significant functional recovery. We propose that restoration of normal integrity of the operational modules of the self-referential brain network may underlie the positive dynamics of 3 aspects of selfhood and provide a neurobiological mechanism for their recovery. The results are discussed in the context of recent experimental studies that support this inference. Studies of ongoing recovery after severe brain injury utilizing knowledge about each separate aspect of complex selfhood will likely help to develop more efficient and targeted rehabilitation programs for patients with brain trauma.

Biological mechanisms of non-linear dose-response for respirable mineral fibers.

PubMed

Cox, Louis Anthony Tony

2018-06-19

Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds. Copyright © 2018. Published by Elsevier Inc.

“The Mind Is Its Own Place”: Amelioration of Claustrophobia in Semantic Dementia

PubMed Central

Clark, Camilla N.; Downey, Laura E.; Golden, Hannah L.; Fletcher, Phillip D.; Cifelli, Alberto; Warren, Jason D.

2014-01-01

Phobias are among the few intensely fearful experiences we regularly have in our everyday lives, yet the brain basis of phobic responses remains incompletely understood. Here we describe the case of a 71-year-old patient with a typical clinicoanatomical syndrome of semantic dementia led by selective (predominantly right-sided) temporal lobe atrophy, who showed striking amelioration of previously disabling claustrophobia following onset of her cognitive syndrome. We interpret our patient's newfound fearlessness as an interaction of damaged limbic and autonomic responsivity with loss of the cognitive meaning of previously threatening situations. This case has implications for our understanding of brain network disintegration in semantic dementia and the neurocognitive basis of phobias more generally. PMID:24825962

How Networks of Informal Trails Cause Landscape Level Damage to Vegetation.

PubMed

Barros, Agustina; Marina Pickering, Catherine

2017-07-01

When visitors are not constrained to remain on formal trails, informal trail networks can develop and damage plant communities in protected areas. These networks can form in areas with low growing vegetation, where formal trails are limited, where there is limited regulation and where vegetation is slow to recover once disturbed. To demonstrate the extent of impacts from unregulated recreational use, we assessed damage to alpine vegetation by hikers and pack animals in the highest protected area in the southern Hemisphere: Aconcagua Park, in the Andes. Within the 237 ha area surveyed in the Horcones Valley, over 19 km of trails were found, nearly all of which (94%) were informal. This network of trails resulted in the direct loss of 11.5 ha of vegetation and extensive fragmentation of alpine meadows (21 fragments) and steppe vegetation (68 fragments). When levels of disturbance off these trails were quantified using rapid visual assessments, 81% of 102 randomly located plots showed evidence of disturbance, with the severity of disturbance greatest close to trails. As a result, vegetation in 90% of the Valley has been damaged by visitor use, nearly all of it from unregulated use. These results highlight the extent to which informal trails and trampling off-trail can cause landscape damage to areas of high conservation value, and hence the importance of better regulation of visitor use. The methodology used for off-trail impact assessment can be easily applied or adapted for other popular protected areas where trampling off-trail is also an issue.

Metabolic responses induced by DNA damage and poly (ADP-ribose) polymerase (PARP) inhibition in MCF-7 cells

PubMed Central

Bhute, Vijesh J.; Palecek, Sean P.

2015-01-01

Genomic instability is one of the hallmarks of cancer. Several chemotherapeutic drugs and radiotherapy induce DNA damage to prevent cancer cell replication. Cells in turn activate different DNA damage response (DDR) pathways to either repair the damage or induce cell death. These DDR pathways also elicit metabolic alterations which can play a significant role in the proper functioning of the cells. The understanding of these metabolic effects resulting from different types of DNA damage and repair mechanisms is currently lacking. In this study, we used NMR metabolomics to identify metabolic pathways which are altered in response to different DNA damaging agents. By comparing the metabolic responses in MCF-7 cells, we identified the activation of poly (ADP-ribose) polymerase (PARP) in methyl methanesulfonate (MMS)-induced DNA damage. PARP activation led to a significant depletion of NAD+. PARP inhibition using veliparib (ABT-888) was able to successfully restore the NAD+ levels in MMS-treated cells. In addition, double strand break induction by MMS and veliparib exhibited similar metabolic responses as zeocin, suggesting an application of metabolomics to classify the types of DNA damage responses. This prediction was validated by studying the metabolic responses elicited by radiation. Our findings indicate that cancer cell metabolic responses depend on the type of DNA damage responses and can also be used to classify the type of DNA damage. PMID:26478723

Solexa sequencing and custom microRNA chip reveal repertoire of microRNAs in mammary gland of bovine suffering from natural infectious mastitis.

PubMed

Ju, Zhihua; Jiang, Qiang; Liu, Gang; Wang, Xiuge; Luo, Guojing; Zhang, Yan; Zhang, Jibin; Zhong, Jifeng; Huang, Jinming

2018-02-01

Identification of microRNAs (miRNAs), target genes and regulatory networks associated with innate immune and inflammatory responses and tissue damage is essential to elucidate the molecular and genetic mechanisms for resistance to mastitis. In this study, a combination of Solexa sequencing and custom miRNA chip approaches was used to profile the expression of miRNAs in bovine mammary gland at the late stage of natural infection with Staphylococcus aureus, a widespread mastitis pathogen. We found 383 loci corresponding to 277 known and 49 putative novel miRNAs, two potential mitrons and 266 differentially expressed miRNAs in the healthy and mastitic cows' mammary glands. Several interaction networks and regulators involved in mastitis susceptibility, such as ALCAM, COL1A1, APOP4, ITIH4, CRP and fibrinogen alpha (FGA), were highlighted. Significant down-regulation and location of bta-miR-26a, which targets FGA in the mastitic mammary glands, were validated using quantitative real-time PCR, in situ hybridization and dual-luciferase reporter assays. We propose that the observed miRNA variations in mammary glands of mastitic cows are related to the maintenance of immune and defense responses, cell proliferation and apoptosis, and tissue injury and healing during the late stage of infection. Furthermore, the effect of bta-miR-26a in mastitis, mediated at least in part by enhancing FGA expression, involves host defense, inflammation and tissue damage. © 2018 Stichting International Foundation for Animal Genetics.

Bioinspired self-healing materials: lessons from nature

PubMed Central

Cremaldi, Joseph C

2018-01-01

Healing is an intrinsic ability in the incredibly biodiverse populations of the plant and animal kingdoms created through evolution. Plants and animals approach healing in similar ways but with unique pathways, such as damage containment in plants or clotting in animals. After analyzing the examples of healing and defense mechanisms found in living nature, eight prevalent mechanisms were identified: reversible muscle control, clotting, cellular response, layering, protective surfaces, vascular networks or capsules, exposure, and replenishable functional coatings. Then the relationship between these mechanisms, nature’s best (evolutionary) methods of mitigating and healing damage, and existing technology in self-healing materials are described. The goals of this top-level overview are to provide a framework for relating the behavior seen in living nature to bioinspired materials, act as a resource to addressing the limitations/problems with existing materials, and open up new avenues of insight and research into self-healing materials. PMID:29600152

On the effect of memory in one-dimensional K=4 automata on networks

NASA Astrophysics Data System (ADS)

Alonso-Sanz, Ramón; Cárdenas, Juan Pablo

2008-12-01

The effect of implementing memory in cells of one-dimensional CA, and on nodes of various types of automata on networks with increasing degrees of random rewiring is studied in this article, paying particular attention to the case of four inputs. As a rule, memory induces a moderation in the rate of changing nodes and in the damage spreading, albeit in the latter case memory turns out to be ineffective in the control of the damage as the wiring network moves away from the ordered structure that features proper one-dimensional CA. This article complements the previous work done in the two-dimensional context.

Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and Contributes to Increased DNA Damage Sensitivity

PubMed Central

Wang, Shu-Huei; Lin, Pei-Ya; Chiu, Ya-Chen; Huang, Ju-Sui; Kuo, Yi-Tsen; Wu, Jen-Chine; Chen, Chin-Chuan

2015-01-01

Chemo- and radiotherapy cause multiple forms of DNA damage and lead to the death of cancer cells. Inhibitors of the DNA damage response are candidate drugs for use in combination therapies to increase the efficacy of such treatments. In this study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA damage by counteracting the DNA damage response. Following DNA damage, the Mec1-dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded by curcumin, which results in deficiencies in double-stand break repair. Additive effects on damage-induced apoptosis and the inhibition of damage-induced autophagy by curcumin were observed. Moreover, rpd3 mutants were found to mimic the curcumin-induced suppression of the DNA damage response. In contrast, hat1 mutants were resistant to DNA damage, and Rad52 degradation was impaired following curcumin treatment. These results indicate that the histone deacetylase inhibitor activity of curcumin is critical to DSB repair and DNA damage sensitivity. PMID:26218133

Adaptive Piezoelectric Circuitry Sensor Network with High-Frequency Harmonics Interrogation for Structural Damage Detection

DTIC Science & Technology

2014-09-17

AFRL-OSR-VA-TR-2014-0255 ADAPTIVE PIEZOELECTRIC CIRCUITRY SENSOR NETWORK KON -WELL WANG MICHIGAN UNIV ANN ARBOR Final Report 09/17/2014 DISTRIBUTION A...Harmonics Interrogation for Structural Damage Detection FA9550-11-1-0072 Kon -Well Wang and Jiong Tang The Regents of the University of Michigan, 3003...mechanism. These efforts have yielded a complete methodology of adaptive high-frequency piezoelectric self-sensing interrogation. None None None SAR Kon

Flash-sourcing or the rapid detection and characterisation of earthquake effects through clickstream data analysis

NASA Astrophysics Data System (ADS)

Bossu, R.; Mazet-Roux, G.; Roussel, F.; Frobert, L.

2011-12-01

Rapid characterisation of earthquake effects is essential for a timely and appropriate response in favour of victims and/or of eyewitnesses. In case of damaging earthquakes, any field observations that can fill the information gap characterising their immediate aftermath can contribute to more efficient rescue operations. This paper presents the last developments of a method called "flash-sourcing" addressing these issues. It relies on eyewitnesses, the first informed and the first concerned by an earthquake occurrence. More precisely, their use of the EMSC earthquake information website (www.emsc-csem.org) is analysed in real time to map the area where the earthquake was felt and identify, at least under certain circumstances zones of widespread damage. The approach is based on the natural and immediate convergence of eyewitnesses on the website who rush to the Internet to investigate cause of the shaking they just felt causing our traffic to increase The area where an earthquake was felt is mapped simply by locating Internet Protocol (IP) addresses during traffic surges. In addition, the presence of eyewitnesses browsing our website within minutes of an earthquake occurrence excludes the possibility of widespread damage in the localities they originate from: in case of severe damage, the networks would be down. The validity of the information derived from this clickstream analysis is confirmed by comparisons with EMS98 macroseismic map obtained from online questionnaires. The name of this approach, "flash-sourcing", is a combination of "flash-crowd" and "crowdsourcing" intending to reflect the rapidity of the data collation from the public. For computer scientists, a flash-crowd names a traffic surge on a website. Crowdsourcing means work being done by a "crowd" of people; It also characterises Internet and mobile applications collecting information from the public such as online macroseismic questionnaires. Like crowdsourcing techniques, flash-sourcing is a crowd-to-agency system, but unlike them it is not based on declarative information (e.g. answers to a questionnaire) but on implicit data, clickstream observed on our website. We present first the main improvements of the method, improved detection of traffic surges, and a way to instantly map areas affected by severe damage or network disruptions. The second part describes how the derived information improves and fastens public earthquake information and, beyond seismology, what it can teach us on public behaviour when facing an earthquake. Finally, the discussion will focus on the future evolutions and how flash-sourcing could ultimately improve earthquake response.

Neural basis of bilingual language control.

PubMed

Calabria, Marco; Costa, Albert; Green, David W; Abutalebi, Jubin

2018-06-19

Acquiring and speaking a second language increases demand on the processes of language control for bilingual as compared to monolingual speakers. Language control for bilingual speakers involves the ability to keep the two languages separated to avoid interference and to select one language or the other in a given conversational context. This ability is what we refer with the term "bilingual language control" (BLC). It is now well established that the architecture of this complex system of language control encompasses brain networks involving cortical and subcortical structures, each responsible for different cognitive processes such as goal maintenance, conflict monitoring, interference suppression, and selective response inhibition. Furthermore, advances have been made in determining the overlap between the BLC and the nonlinguistic executive control networks, under the hypothesis that the BLC processes are just an instantiation of a more domain-general control system. Here, we review the current knowledge about the neural basis of these control systems. Results from brain imaging studies of healthy adults and on the performance of bilingual individuals with brain damage are discussed. © 2018 New York Academy of Sciences.

Activity-Dependent NPAS4 Expression and the Regulation of Gene Programs Underlying Plasticity in the Central Nervous System

PubMed Central

2013-01-01

The capability of the brain to change functionally in response to sensory experience is most active during early stages of development but it decreases later in life when major alterations of neuronal network structures no longer take place in response to experience. This view has been recently challenged by experimental strategies based on the enhancement of environmental stimulation levels, genetic manipulations, and pharmacological treatments, which all have demonstrated that the adult brain retains a degree of plasticity that allows for a rewiring of neuronal circuitries over the entire life course. A hot spot in the field of neuronal plasticity centres on gene programs that underlie plastic phenomena in adulthood. Here, I discuss the role of the recently discovered neuronal-specific and activity-dependent transcription factor NPAS4 as a critical mediator of plasticity in the nervous system. A better understanding of how modifications in the connectivity of neuronal networks occur may shed light on the treatment of pathological conditions such as brain damage or disease in adult life, some of which were once considered untreatable. PMID:24024041

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

NASA Technical Reports Server (NTRS)

Bosworth, John T.; Williams-Hayes, Peggy S.

2007-01-01

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented.

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

NASA Technical Reports Server (NTRS)

Bosworth, John T.; Williams-Hayes, Peggy S.

2010-01-01

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented.

Real-time earthquake shake, damage, and loss mapping for Istanbul metropolitan area

NASA Astrophysics Data System (ADS)

Zülfikar, A. Can; Fercan, N. Özge Zülfikar; Tunç, Süleyman; Erdik, Mustafa

2017-01-01

The past devastating earthquakes in densely populated urban centers, such as the 1994 Northridge; 1995 Kobe; 1999 series of Kocaeli, Düzce, and Athens; and 2011 Van-Erciş events, showed that substantial social and economic losses can be expected. Previous studies indicate that inadequate emergency response can increase the number of casualties by a maximum factor of 10, which suggests the need for research on rapid earthquake shaking damage and loss estimation. The reduction in casualties in urban areas immediately following an earthquake can be improved if the location and severity of damages can be rapidly assessed by information from rapid response systems. In this context, a research project (TUBITAK-109M734) titled "Real-time Information of Earthquake Shaking, Damage, and Losses for Target Cities of Thessaloniki and Istanbul" was conducted during 2011-2014 to establish the rapid estimation of ground motion shaking and related earthquake damages and casualties for the target cities. In the present study, application to Istanbul metropolitan area is presented. In order to fulfill this objective, earthquake hazard and risk assessment methodology known as Earthquake Loss Estimation Routine, which was developed for the Euro-Mediterranean region within the Network of Research Infrastructures for European Seismology EC-FP6 project, was used. The current application to the Istanbul metropolitan area provides real-time ground motion information obtained by strong motion stations distributed throughout the densely populated areas of the city. According to this ground motion information, building damage estimation is computed by using grid-based building inventory, and the related loss is then estimated. Through this application, the rapidly estimated information enables public and private emergency management authorities to take action and allocate and prioritize resources to minimize the casualties in urban areas during immediate post-earthquake periods. Moreover, it is expected that during an earthquake, rapid information of ground shaking, damage, and loss estimations will provide vital information to allow appropriate emergency agencies to take immediate action, which will help to save lives. In general terms, this study can be considered as an example for application to metropolitan areas under seismic risk.

Damage Diagnosis in Semiconductive Materials Using Electrical Impedance Measurements

NASA Technical Reports Server (NTRS)

Ross, Richard W.; Hinton, Yolanda L.

2008-01-01

Recent aerospace industry trends have resulted in an increased demand for real-time, effective techniques for in-flight structural health monitoring. A promising technique for damage diagnosis uses electrical impedance measurements of semiconductive materials. By applying a small electrical current into a material specimen and measuring the corresponding voltages at various locations on the specimen, changes in the electrical characteristics due to the presence of damage can be assessed. An artificial neural network uses these changes in electrical properties to provide an inverse solution that estimates the location and magnitude of the damage. The advantage of the electrical impedance method over other damage diagnosis techniques is that it uses the material as the sensor. Simple voltage measurements can be used instead of discrete sensors, resulting in a reduction in weight and system complexity. This research effort extends previous work by employing finite element method models to improve accuracy of complex models with anisotropic conductivities and by enhancing the computational efficiency of the inverse techniques. The paper demonstrates a proof of concept of a damage diagnosis approach using electrical impedance methods and a neural network as an effective tool for in-flight diagnosis of structural damage to aircraft components.

An adaptive molecular timer in p53-meidated cell fate decision

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Peng; Wang, Ping; Liu, Feng; Wang, Wei

The tumor suppressor p53 decides cellular outcomes in the DNA damage response. It is intriguing to explore the link between p53 dynamics and cell fates. We developed a theoretical model of p53 signaling network to clarify the mechanism of cell fate decision mediated by its dynamics. We found that the interplay between p53-Mdm2 negative feedback loop and p53-PTEN-Mdm2 positive feedback loop shapes p53 dynamics. Depending on the intensity of DNA damage, p53 shows three modes of dynamics: persistent pulses, two-phase dynamics with pulses followed by sustained high levels and straightforward high levels. Especially, p53 shows two-phase dynamics upon moderated damage and the required number of p53 pulses before apoptosis induction decreases with increasing DNA damage. Our results suggested there exists an adaptive molecular timer that determines whether and when the apoptosis switch should be triggered. We clarified the mechanism behind the switching of p53 dynamical modes by bifurcation analysis. Moreover, we reproduced the experimental results that drug additions alter p53 pulses to sustained p53 activation and leads to senescence. Our work may advance the understanding the significance of p53 dynamics in tumor suppression. This work was supported by National Natural Science Foundation of China (Nos. 11175084, 11204126 and 31361163003).

Forecast on Water Locking Damage of Low Permeable Reservoir with Quantum Neural Network

NASA Astrophysics Data System (ADS)

Zhao, Jingyuan; Sun, Yuxue; Feng, Fuping; Zhao, Fulei; Sui, Dianjie; Xu, Jianjun

2018-01-01

It is of great importance in oil-gas reservoir protection to timely and correctly forecast the water locking damage, the greatest damage for low permeable reservoir. An analysis is conducted on the production mechanism and various influence factors of water locking damage, based on which a quantum neuron is constructed based on the information processing manner of a biological neuron and the principle of quantum neural algorithm, besides, the quantum neural network model forecasting the water locking of the reservoir is established and related software is also made to forecast the water locking damage of the gas reservoir. This method has overcome the defects of grey correlation analysis that requires evaluation matrix analysis and complicated operation. According to the practice in Longxi Area of Daqing Oilfield, this method is characterized by fast operation, few system parameters and high accuracy rate (the general incidence rate may reach 90%), which can provide reliable support for the protection technique of low permeable reservoir.

The semantic anatomical network: Evidence from healthy and brain-damaged patient populations.

PubMed

Fang, Yuxing; Han, Zaizhu; Zhong, Suyu; Gong, Gaolang; Song, Luping; Liu, Fangsong; Huang, Ruiwang; Du, Xiaoxia; Sun, Rong; Wang, Qiang; He, Yong; Bi, Yanchao

2015-09-01

Semantic processing is central to cognition and is supported by widely distributed gray matter (GM) regions and white matter (WM) tracts. The exact manner in which GM regions are anatomically connected to process semantics remains unknown. We mapped the semantic anatomical network (connectome) by conducting diffusion imaging tractography in 48 healthy participants across 90 GM "nodes," and correlating the integrity of each obtained WM edge and semantic performance across 80 brain-damaged patients. Fifty-three WM edges were obtained whose lower integrity associated with semantic deficits and together with their linked GM nodes constitute a semantic WM network. Graph analyses of this network revealed three structurally segregated modules that point to distinct semantic processing components and identified network hubs and connectors that are central in the communication across the subnetworks. Together, our results provide an anatomical framework of human semantic network, advancing the understanding of the structural substrates supporting semantic processing. © 2015 Wiley Periodicals, Inc.

ELER software - a new tool for urban earthquake loss assessment

NASA Astrophysics Data System (ADS)

Hancilar, U.; Tuzun, C.; Yenidogan, C.; Erdik, M.

2010-12-01

Rapid loss estimation after potentially damaging earthquakes is critical for effective emergency response and public information. A methodology and software package, ELER-Earthquake Loss Estimation Routine, for rapid estimation of earthquake shaking and losses throughout the Euro-Mediterranean region was developed under the Joint Research Activity-3 (JRA3) of the EC FP6 Project entitled "Network of Research Infrastructures for European Seismology-NERIES". Recently, a new version (v2.0) of ELER software has been released. The multi-level methodology developed is capable of incorporating regional variability and uncertainty originating from ground motion predictions, fault finiteness, site modifications, inventory of physical and social elements subjected to earthquake hazard and the associated vulnerability relationships. Although primarily intended for quasi real-time estimation of earthquake shaking and losses, the routine is also equally capable of incorporating scenario-based earthquake loss assessments. This paper introduces the urban earthquake loss assessment module (Level 2) of the ELER software which makes use of the most detailed inventory databases of physical and social elements at risk in combination with the analytical vulnerability relationships and building damage-related casualty vulnerability models for the estimation of building damage and casualty distributions, respectively. Spectral capacity-based loss assessment methodology and its vital components are presented. The analysis methods of the Level 2 module, i.e. Capacity Spectrum Method (ATC-40, 1996), Modified Acceleration-Displacement Response Spectrum Method (FEMA 440, 2005), Reduction Factor Method (Fajfar, 2000) and Coefficient Method (ASCE 41-06, 2006), are applied to the selected building types for validation and verification purposes. The damage estimates are compared to the results obtained from the other studies available in the literature, i.e. SELENA v4.0 (Molina et al., 2008) and ATC-55 (Yang, 2005). An urban loss assessment exercise for a scenario earthquake for the city of Istanbul is conducted and physical and social losses are presented. Damage to the urban environment is compared to the results obtained from similar software, i.e. KOERILoss (KOERI, 2002) and DBELA (Crowley et al., 2004). The European rapid loss estimation tool is expected to help enable effective emergency response, on both local and global level, as well as public information.

A Pressure-Dependent Damage Model for Energetic Materials

DTIC Science & Technology

2013-04-01

appropriate damage nucleation and evolution laws, and the equation of state ) with its reactive response. 15. SUBJECT TERMS pressure-dependent...evolution laws, and the equation of state ) with its reactive response. INTRODUCTION Explosions and deflagrations are classifications of sub-detonative...energetic material’s mechanical response (through the yield criterion, damage evolution and equation of state ) with its reactive response. DAMAGE-FREE

Dynamic fracture network around faults: implications for earthquake ruptures, ground motion and energy budget

NASA Astrophysics Data System (ADS)

Okubo, K.; Bhat, H. S.; Rougier, E.; Lei, Z.; Knight, E. E.; Klinger, Y.

2017-12-01

Numerous studies have suggested that spontaneous earthquake ruptures can dynamically induce failure in secondary fracture network, regarded as damage zone around faults. The feedbacks of such fracture network play a crucial role in earthquake rupture, its radiated wave field and the total energy budget. A novel numerical modeling tool based on the combined finite-discrete element method (FDEM), which accounts for the main rupture propagation and nucleation/propagation of secondary cracks, was used to quantify the evolution of the fracture network and evaluate its effects on the main rupture and its associated radiation. The simulations were performed with the FDEM-based software tool, Hybrid Optimization Software Suite (HOSSedu) developed by Los Alamos National Laboratory. We first modeled an earthquake rupture on a planar strike-slip fault surrounded by a brittle medium where secondary cracks can be nucleated/activated by the earthquake rupture. We show that the secondary cracks are dynamically generated dominantly on the extensional side of the fault, mainly behind the rupture front, and it forms an intricate network of fractures in the damage zone. The rupture velocity thereby significantly decreases, by 10 to 20 percent, while the supershear transition length increases in comparison to the one with purely elastic medium. It is also observed that the high-frequency component (10 to 100 Hz) of the near-field ground acceleration is enhanced by the dynamically activated fracture network, consistent with field observations. We then conducted the case study in depth with various sets of initial stress state, and friction properties, to investigate the evolution of damage zone. We show that the width of damage zone decreases in depth, forming "flower-like" structure as the characteristic slip distance in linear slip-weakening law, or the fracture energy on the fault, is kept constant with depth. Finally, we compared the fracture energy on the fault to the energy absorbed by the secondary fracture network to better understand the earthquake energy budget. We conclude that the secondary fracture network plays an important role on the dynamic earthquake rupture, its radiated wave field and the overall energy budget.

Zebrafish: swimming towards a role for fanconi genes in DNA repair.

PubMed

Scata, Kimberly A; El-Deiry, Wafik S

2004-06-01

The zebrafish, Danio rerio, has become a favorite model organism for geneticists and developmental biologists. Recently cancer biologists have turned to this tiny fish to help them unravel the mysteries of conserved pathways such as the Fanconi Anemia (FA) pathway. Although a relatively rare disease, the genes involved in FA are part of a large network of DNA damage response/repair genes. Liu and colleagues have recapitulated some of the clinical manifestations of human FA by knocking down the zebrafish FANC-D2 gene thereby providing a new model for probing the underlying causes of these phenotypes.

Parallel approach to identifying the well-test interpretation model using a neurocomputer

NASA Astrophysics Data System (ADS)

May, Edward A., Jr.; Dagli, Cihan H.

1996-03-01

The well test is one of the primary diagnostic and predictive tools used in the analysis of oil and gas wells. In these tests, a pressure recording device is placed in the well and the pressure response is recorded over time under controlled flow conditions. The interpreted results are indicators of the well's ability to flow and the damage done to the formation surrounding the wellbore during drilling and completion. The results are used for many purposes, including reservoir modeling (simulation) and economic forecasting. The first step in the analysis is the identification of the Well-Test Interpretation (WTI) model, which determines the appropriate solution method. Mis-identification of the WTI model occurs due to noise and non-ideal reservoir conditions. Previous studies have shown that a feed-forward neural network using the backpropagation algorithm can be used to identify the WTI model. One of the drawbacks to this approach is, however, training time, which can run into days of CPU time on personal computers. In this paper a similar neural network is applied using both a personal computer and a neurocomputer. Input data processing, network design, and performance are discussed and compared. The results show that the neurocomputer greatly eases the burden of training and allows the network to outperform a similar network running on a personal computer.

Revealing the Effect of Irradiation on Cement Hydrates: Evidence of a Topological Self-Organization.

PubMed

Krishnan, N M Anoop; Wang, Bu; Sant, Gaurav; Phillips, James C; Bauchy, Mathieu

2017-09-20

Despite the crucial role of concrete in the construction of nuclear power plants, the effects of radiation exposure (i.e., in the form of neutrons) on the calcium-silicate-hydrate (C-S-H, i.e., the glue of concrete) remain largely unknown. Using molecular dynamics simulations, we systematically investigate the effects of irradiation on the structure of C-S-H across a range of compositions. Expectedly, although C-S-H is more resistant to irradiation than typical crystalline silicates, such as quartz, we observe that radiation exposure affects C-S-H's structural order, silicate mean chain length, and the amount of molecular water that is present in the atomic network. By topological analysis, we show that these "structural effects" arise from a self-organization of the atomic network of C-S-H upon irradiation. This topological self-organization is driven by the (initial) presence of atomic eigenstress in the C-S-H network and is facilitated by the presence of water in the network. Overall, we show that C-S-H exhibits an optimal resistance to radiation damage when its atomic network is isostatic (at Ca/Si = 1.5). Such an improved understanding of the response of C-S-H to irradiation can pave the way to the design of durable concrete for radiation applications.

Structural Health Monitoring of a Composite Panel Based on PZT Sensors and a Transfer Impedance Framework.

PubMed

Dziendzikowski, Michal; Niedbala, Patryk; Kurnyta, Artur; Kowalczyk, Kamil; Dragan, Krzysztof

2018-05-11

One of the ideas for development of Structural Health Monitoring (SHM) systems is based on excitation of elastic waves by a network of PZT piezoelectric transducers integrated with the structure. In the paper, a variant of the so-called Transfer Impedance (TI) approach to SHM is followed. Signal characteristics, called the Damage Indices (DIs), were proposed for data presentation and analysis. The idea underlying the definition of DIs was to maintain most of the information carried by the voltage induced on PZT sensors by elastic waves. In particular, the DIs proposed in the paper should be sensitive to all types of damage which can influence the amplitude or the phase of the voltage induced on the sensor. Properties of the proposed DIs were investigated experimentally using a GFRP composite panel equipped with PZT networks attached to its surface and embedded into its internal structure. Repeatability and stability of DI indications under controlled conditions were verified in tests. Also, some performance indicators for surface-attached and structure-embedded sensors were obtained. The DIs' behavior was dependent mostly on the presence of a simulated damage in the structure. Anisotropy of mechanical properties of the specimen, geometrical properties of PZT network as well as, to some extent, the technology of sensor integration with the structure were irrelevant for damage indication. This property enables the method to be used for damage detection and classification.

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

Gecow, Andrzej

On the way to simulating adaptive evolution of complex system describing a living object or human developed project, a fitness should be defined on node states or network external outputs. Feedbacks lead to circular attractors of these states or outputs which make it difficult to define a fitness. The main statistical effects of adaptive condition are the result of small change tendency and to appear, they only need a statistically correct size of damage initiated by evolutionary change of system. This observation allows to cut loops of feedbacks and in effect to obtain a particular statistically correct state instead ofmore » a long circular attractor which in the quenched model is expected for chaotic network with feedback. Defining fitness on such states is simple. We calculate only damaged nodes and only once. Such an algorithm is optimal for investigation of damage spreading i.e. statistical connections of structural parameters of initial change with the size of effected damage. It is a reversed-annealed method--function and states (signals) may be randomly substituted but connections are important and are preserved. The small damages important for adaptive evolution are correctly depicted in comparison to Derrida annealed approximation which expects equilibrium levels for large networks. The algorithm indicates these levels correctly. The relevant program in Pascal, which executes the algorithm for a wide range of parameters, can be obtained from the author.« less

Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen*

PubMed Central

Kozlov, Sergei V.; Waardenberg, Ashley J.; Engholm-Keller, Kasper; Arthur, Jonathan W.; Graham, Mark E.; Lavin, Martin

2016-01-01

Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM-dependence for translocation from the cytoplasm to the nucleus. These data provide new insights into the activation of ATM by oxidative stress through identification of novel substrates for ATM in the cytoplasm. PMID:26699800

Acoustic emission localization based on FBG sensing network and SVR algorithm

NASA Astrophysics Data System (ADS)

Sai, Yaozhang; Zhao, Xiuxia; Hou, Dianli; Jiang, Mingshun

2017-03-01

In practical application, carbon fiber reinforced plastics (CFRP) structures are easy to appear all sorts of invisible damages. So the damages should be timely located and detected for the safety of CFPR structures. In this paper, an acoustic emission (AE) localization system based on fiber Bragg grating (FBG) sensing network and support vector regression (SVR) is proposed for damage localization. AE signals, which are caused by damage, are acquired by high speed FBG interrogation. According to the Shannon wavelet transform, time differences between AE signals are extracted for localization algorithm based on SVR. According to the SVR model, the coordinate of AE source can be accurately predicted without wave velocity. The FBG system and localization algorithm are verified on a 500 mm×500 mm×2 mm CFRP plate. The experimental results show that the average error of localization system is 2.8 mm and the training time is 0.07 s.

Epithelial and endothelial damage induced by mechanical ventilation modes.

PubMed

Suki, Béla; Hubmayr, Rolf

2014-02-01

The adult respiratory distress syndrome (ARDS) is a common cause of respiratory failure with substantial impact on public health. Patients with ARDS generally require mechanical ventilation, which risks further lung damage. Recent improvements in ARDS outcomes have been attributed to reductions in deforming stress associated with lung protective mechanical ventilation modes and settings. The following review details the mechanics of the lung parenchyma at different spatial scales and the response of its resident cells to deforming stress in order to provide the biologic underpinnings of lung protective care. Although lung injury is typically viewed through the lens of altered barrier properties and mechanical ventilation-associated immune responses, in this review, we call attention to the importance of heterogeneity and the physical failure of the load bearing cell and tissue elements in the pathogenesis of ARDS. Specifically, we introduce a simple elastic network model to better understand the deformations of lung regions, intra-acinar alveoli and cells within a single alveolus, and consider the role of regional distension and interfacial stress-related injury for various ventilation modes. Heterogeneity of stiffness and intercellular and intracellular stress failure are fundamental components of ARDS and their development also depends on the ventilation mode.

Antimicrobial Histones and DNA Traps in Invertebrate Immunity

PubMed Central

Poirier, Aurore C.; Schmitt, Paulina; Rosa, Rafael D.; Vanhove, Audrey S.; Kieffer-Jaquinod, Sylvie; Rubio, Tristan P.; Charrière, Guillaume M.; Destoumieux-Garzón, Delphine

2014-01-01

Although antimicrobial histones have been isolated from multiple metazoan species, their role in host defense has long remained unanswered. We found here that the hemocytes of the oyster Crassostrea gigas release antimicrobial H1-like and H5-like histones in response to tissue damage and infection. These antimicrobial histones were shown to be associated with extracellular DNA networks released by hemocytes, the circulating immune cells of invertebrates, in response to immune challenge. The hemocyte-released DNA was found to surround and entangle vibrios. This defense mechanism is reminiscent of the neutrophil extracellular traps (ETs) recently described in vertebrates. Importantly, oyster ETs were evidenced in vivo in hemocyte-infiltrated interstitial tissues surrounding wounds, whereas they were absent from tissues of unchallenged oysters. Consistently, antimicrobial histones were found to accumulate in oyster tissues following injury or infection with vibrios. Finally, oyster ET formation was highly dependent on the production of reactive oxygen species by hemocytes. This shows that ET formation relies on common cellular and molecular mechanisms from vertebrates to invertebrates. Altogether, our data reveal that ET formation is a defense mechanism triggered by infection and tissue damage, which is shared by relatively distant species suggesting either evolutionary conservation or convergent evolution within Bilateria. PMID:25037219

The role of rare innate immune cells in Type 2 immune activation against parasitic helminths.

PubMed

Webb, Lauren M; Tait Wojno, Elia D

2017-09-01

The complexity of helminth macroparasites is reflected in the intricate network of host cell types that participate in the Type 2 immune response needed to battle these organisms. In this context, adaptive T helper 2 cells and the Type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have been the focus of research for years, but recent work has demonstrated that the innate immune system plays an essential role. Some innate immune cells that promote Type 2 immunity are relatively abundant, such as macrophages and eosinophils. However, we now appreciate that more rare cell types including group 2 innate lymphoid cells, basophils, mast cells and dendritic cells make significant contributions to these responses. These cells are found at low frequency but they are specialized to their roles - located at sites such as the skin, lung and gut, where the host combats helminth parasites. These cells respond rapidly and robustly to worm antigens and worm-induced damage to produce essential cytokines, chemokines, eicosanoids and histamine to activate damaged epithelium and to recruit other effectors. Thus, a greater understanding of how these cells operate is essential to understand how the host protects itself during helminth infection.

78 FR 56939 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-Opendaylight...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-16

... of antitrust plaintiffs to actual damages under specified circumstances. Specifically, Adva Optical Networking SE., Munich, Germany; Versa Networks, Santa Clara, CA; Guavus, San Mateo, CA; Pantheon.... In addition, Big Switch Networks, Mountain View, CA has withdrawn as a party to this venture. No...

Plant Perception and Short-Term Responses to Phytophagous Insects and Mites.

PubMed

Santamaria, M Estrella; Arnaiz, Ana; Gonzalez-Melendi, Pablo; Martinez, Manuel; Diaz, Isabel

2018-05-03

Plant⁻pest relationships involve complex processes encompassing a network of molecules, signals, and regulators for overcoming defenses they develop against each other. Phytophagous arthropods identify plants mainly as a source of food. In turn, plants develop a variety of strategies to avoid damage and survive. The success of plant defenses depends on rapid and specific recognition of the phytophagous threat. Subsequently, plants trigger a cascade of short-term responses that eventually result in the production of a wide range of compounds with defense properties. This review deals with the main features involved in the interaction between plants and phytophagous insects and acari, focusing on early responses from the plant side. A general landscape of the diverse strategies employed by plants within the first hours after pest perception to block the capability of phytophagous insects to develop mechanisms of resistance is presented, with the potential of providing alternatives for pest control.

RecA-mediated SOS response provides a geraniol tolerance in Escherichia coli.

PubMed

Shah, Asad Ali; Wang, Chonglong; Yoon, Sang-Hwal; Kim, Jae-Yean; Choi, Eui-Sung; Kim, Seon-Won

2013-09-20

Geraniol is an important industrial material and a potential candidate of advanced biofuels. One challenge of microbial geraniol production is the toxicity to hosts. However, the poor understanding on geraniol tolerance mechanism is an obstacle for developing geraniol tolerant host. This study genome-widely screened a shot-gun DNA library of Escherichia coli and found that recA is able to confer geraniol tolerance in E. coli. The recA knockout mutant was found extremely sensitive to geraniol. Based on our data, it was deciphered that recA provided tolerance through SOS response network responding to DNA damage caused by geraniol. RecA-mediated SOS response activates the homologous recombinational repair by RecB and RecN for corrective DNA maintenance. This protection mechanism suggests an effective strategy to combat geraniol toxicity in E. coli. Copyright © 2013 Elsevier B.V. All rights reserved.

Compressive sensing for efficient health monitoring and effective damage detection of structures

NASA Astrophysics Data System (ADS)

Jayawardhana, Madhuka; Zhu, Xinqun; Liyanapathirana, Ranjith; Gunawardana, Upul

2017-02-01

Real world Structural Health Monitoring (SHM) systems consist of sensors in the scale of hundreds, each sensor generating extremely large amounts of data, often arousing the issue of the cost associated with data transfer and storage. Sensor energy is a major component included in this cost factor, especially in Wireless Sensor Networks (WSN). Data compression is one of the techniques that is being explored to mitigate the effects of these issues. In contrast to traditional data compression techniques, Compressive Sensing (CS) - a very recent development - introduces the means of accurately reproducing a signal by acquiring much less number of samples than that defined by Nyquist's theorem. CS achieves this task by exploiting the sparsity of the signal. By the reduced amount of data samples, CS may help reduce the energy consumption and storage costs associated with SHM systems. This paper investigates CS based data acquisition in SHM, in particular, the implications of CS on damage detection and localization. CS is implemented in a simulation environment to compress structural response data from a Reinforced Concrete (RC) structure. Promising results were obtained from the compressed data reconstruction process as well as the subsequent damage identification process using the reconstructed data. A reconstruction accuracy of 99% could be achieved at a Compression Ratio (CR) of 2.48 using the experimental data. Further analysis using the reconstructed signals provided accurate damage detection and localization results using two damage detection algorithms, showing that CS has not compromised the crucial information on structural damages during the compression process.

Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients

PubMed Central

Vanhaudenhuyse, Audrey; Noirhomme, Quentin; Tshibanda, Luaba J.-F.; Bruno, Marie-Aurelie; Boveroux, Pierre; Schnakers, Caroline; Soddu, Andrea; Perlbarg, Vincent; Ledoux, Didier; Brichant, Jean-François; Moonen, Gustave; Maquet, Pierre; Greicius, Michael D.

2010-01-01

The ‘default network’ is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient’s default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. PMID:20034928

CPTAC Develops Fit-for-Purpose Multiplex Immuno-MRM Assay for Profiling the DNA Damage Response Pathway | Office of Cancer Clinical Proteomics Research

Cancer.gov

Ionizing radiation (IR) is a commonly employed cancer treatment that kills cancer cells by damaging their DNA. While the DNA damage response (DDR) pathway may be key to determining tumor responses, radiochemical damage due to IR can target the patients’ healthy dividing cells, leading to the formation of secondary hematologic and solid tumors after DNA-damaging therapy.

USP7S-dependent inactivation of Mule regulates DNA damage signalling and repair.

PubMed

Khoronenkova, Svetlana V; Dianov, Grigory L

2013-02-01

The E3 ubiquitin ligase Mule/ARF-BP1 plays an important role in the cellular DNA damage response by controlling base excision repair and p53 protein levels. However, how the activity of Mule is regulated in response to DNA damage is currently unknown. Here, we report that the Ser18-containing isoform of the USP7 deubiquitylation enzyme (USP7S) controls Mule stability by preventing its self-ubiquitylation and subsequent proteasomal degradation. We find that in response to DNA damage, downregulation of USP7S leads to self-ubiquitylation and proteasomal degradation of Mule, which eventually leads to p53 accumulation. Cells that are unable to downregulate Mule show reduced ability to upregulate p53 levels in response to DNA damage. We also find that, as Mule inactivation is required for stabilization of base excision repair enzymes, the failure of cells to downregulate Mule after DNA damage results in deficient DNA repair. Our data describe a novel mechanism by which Mule is regulated in response to DNA damage and coordinates cellular DNA damage responses and DNA repair.

Towards Automated Analysis of Urban Infrastructure after Natural Disasters using Remote Sensing

NASA Astrophysics Data System (ADS)

Axel, Colin

Natural disasters, such as earthquakes and hurricanes, are an unpreventable component of the complex and changing environment we live in. Continued research and advancement in disaster mitigation through prediction of and preparation for impacts have undoubtedly saved many lives and prevented significant amounts of damage, but it is inevitable that some events will cause destruction and loss of life due to their sheer magnitude and proximity to built-up areas. Consequently, development of effective and efficient disaster response methodologies is a research topic of great interest. A successful emergency response is dependent on a comprehensive understanding of the scenario at hand. It is crucial to assess the state of the infrastructure and transportation network, so that resources can be allocated efficiently. Obstructions to the roadways are one of the biggest inhibitors to effective emergency response. To this end, airborne and satellite remote sensing platforms have been used extensively to collect overhead imagery and other types of data in the event of a natural disaster. The ability of these platforms to rapidly probe large areas is ideal in a situation where a timely response could result in saving lives. Typically, imagery is delivered to emergency management officials who then visually inspect it to determine where roads are obstructed and buildings have collapsed. Manual interpretation of imagery is a slow process and is limited by the quality of the imagery and what the human eye can perceive. In order to overcome the time and resource limitations of manual interpretation, this dissertation inves- tigated the feasibility of performing fully automated post-disaster analysis of roadways and buildings using airborne remote sensing data. First, a novel algorithm for detecting roadway debris piles from airborne light detection and ranging (lidar) point clouds and estimating their volumes is presented. Next, a method for detecting roadway flooding in aerial imagery and estimating the depth of the water using digital elevation models (DEMs) is introduced. Finally, a technique for assessing building damage from airborne lidar point clouds is presented. All three methods are demonstrated using remotely sensed data that were collected in the wake of recent natural disasters. The research presented in this dissertation builds a case for the use of automatic, algorithmic analysis of road networks and buildings after a disaster. By reducing the latency between the disaster and the delivery of damage maps needed to make executive decisions about resource allocation and performing search and rescue missions, significant loss reductions could be achieved.

PARP inhibitors--current status and the walk towards early breast cancer.

PubMed

Glendenning, Jennifer; Tutt, Andrew

2011-10-01

Epithelial carcinomas in general arise as a result of the acquisition of and selection for multiple mutations in a parental somatic cell clone within the tissues of the primary organ of origin. In the last two decades genome caretakers, which function in key areas of DNA damage response, have been recognized as important tumour suppressor genes. Inactivating mutations in these genes occur both as germline and/or somatic mutations with increasing evidence of epigenetic silencing as an additional cause of loss of function. In any event, loss of function in a tumour cell pre-cursor clone leads to accelerated mutation acquisition and underpins the aetiology of the tumour. With increasing understanding of the complex network that is the DNA damage response, signaling pathways already recognized to be central to the establishment of the cancer phenotype are gaining additional roles as controllers of DNA repair. This has relevance to identification of wider populations of patients with tumours susceptible to approaches that target DNA repair deficiency. These have classically been with DNA damaging chemotherapy but the recently developed small molecule inhibitors of DNA repair enzymes such as Poly-ADP polymerases PARP-1 and PARP-2 have been shown to target tumour deficiencies in DNA repair as well sensitizing to DNA damaging therapeutics such as radiation and chemotherapy. Early phase trials with efficacy endpoints have been presented for the PARP inhibitors AG014699, olaparib, veliparib, iniparib and MK4827. The results of the first phase II trials exploring monotherapy PARP inhibitor strategies, which are based on revisiting the concept of synthetic lethality, have emerged and are reviewed herein. The clinical trials that have or are exploring combinations with DNA damaging therapy in these contexts are discussed with particular reference to breast cancer, as are biomarkers that have been proposed and are being investigated to develop optimal drug schedule and patient selection criteria for these DNA repair targeting approaches. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stabilization of perturbed Boolean network attractors through compensatory interactions

PubMed Central

2014-01-01

Background Understanding and ameliorating the effects of network damage are of significant interest, due in part to the variety of applications in which network damage is relevant. For example, the effects of genetic mutations can cascade through within-cell signaling and regulatory networks and alter the behavior of cells, possibly leading to a wide variety of diseases. The typical approach to mitigating network perturbations is to consider the compensatory activation or deactivation of system components. Here, we propose a complementary approach wherein interactions are instead modified to alter key regulatory functions and prevent the network damage from triggering a deregulatory cascade. Results We implement this approach in a Boolean dynamic framework, which has been shown to effectively model the behavior of biological regulatory and signaling networks. We show that the method can stabilize any single state (e.g., fixed point attractors or time-averaged representations of multi-state attractors) to be an attractor of the repaired network. We show that the approach is minimalistic in that few modifications are required to provide stability to a chosen attractor and specific in that interventions do not have undesired effects on the attractor. We apply the approach to random Boolean networks, and further show that the method can in some cases successfully repair synchronous limit cycles. We also apply the methodology to case studies from drought-induced signaling in plants and T-LGL leukemia and find that it is successful in both stabilizing desired behavior and in eliminating undesired outcomes. Code is made freely available through the software package BooleanNet. Conclusions The methodology introduced in this report offers a complementary way to manipulating node expression levels. A comprehensive approach to evaluating network manipulation should take an "all of the above" perspective; we anticipate that theoretical studies of interaction modification, coupled with empirical advances, will ultimately provide researchers with greater flexibility in influencing system behavior. PMID:24885780

The NASA F-15 Intelligent Flight Control Systems: Generation II

NASA Technical Reports Server (NTRS)

Buschbacher, Mark; Bosworth, John

2006-01-01

The Second Generation (Gen II) control system for the F-15 Intelligent Flight Control System (IFCS) program implements direct adaptive neural networks to demonstrate robust tolerance to faults and failures. The direct adaptive tracking controller integrates learning neural networks (NNs) with a dynamic inversion control law. The term direct adaptive is used because the error between the reference model and the aircraft response is being compensated or directly adapted to minimize error without regard to knowing the cause of the error. No parameter estimation is needed for this direct adaptive control system. In the Gen II design, the feedback errors are regulated with a proportional-plus-integral (PI) compensator. This basic compensator is augmented with an online NN that changes the system gains via an error-based adaptation law to improve aircraft performance at all times, including normal flight, system failures, mispredicted behavior, or changes in behavior resulting from damage.

The Role of Mitophagy in Innate Immunity

PubMed Central

Gkikas, Ilias; Palikaras, Konstantinos; Tavernarakis, Nektarios

2018-01-01

Mitochondria are cellular organelles essential for multiple biological processes, including energy production, metabolites biosynthesis, cell death, and immunological responses among others. Recent advances in the field of immunology research reveal the pivotal role of energy metabolism in innate immune cells fate and function. Therefore, the maintenance of mitochondrial network integrity and activity is a prerequisite for immune system homeostasis. Mitochondrial selective autophagy, known as mitophagy, surveils mitochondrial population eliminating superfluous and/or impaired organelles and mediating cellular survival and viability in response to injury/trauma and infection. Defective removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and subsequently to chronic systemic inflammation and development of inflammatory diseases. Here, we review the molecular mechanisms of mitophagy and highlight its critical role in the innate immune system homeostasis.

Long-term change of site response after the M W 9.0 Tohoku earthquake in Japan

NASA Astrophysics Data System (ADS)

Wu, Chunquan; Peng, Zhigang

2012-12-01

The recent M W 9.0 off the Pacific coast of Tohoku earthquake is the largest recorded earthquake in Japan's history. The Tohoku main shock and its aftershocks generated widespread strong shakings as large as ~3000 Gal along the east coast of Japan. Wu and Peng (2011) found clear drop of resonant frequency of up to 70% during the Tohoku main shock at 6 sites and correlation of resonance (peak) frequency and peak ground acceleration (PGA) during the main shock. Here we follow that study and systematically analyze long-term changes of material properties in the shallow crust from one year before to 5 months after the Tohoku main shock, using seismic data recorded by the Japanese Strong Motion Network KiK-Net. We use sliding window spectral ratios computed from a pair of surface and borehole stations to track the temporal changes in the site response of 6 sites. Our results show two stages of logarithmic recovery after a sharp drop of resonance frequency during the Tohoku main shock. The first stage is a rapid recovery within several hundred seconds to several hours, and the second stage is a slow recovery of more than five months. We also investigate whether the damage caused by the Tohoku main shock could make the near surface layers more susceptible to further damages, but we do not observe clear changes in susceptibility to further damage before and after the Tohoku main shock.

Acoustic Emission of Large PRSEUS Structures (Pultruded Rod Stitched Efficient Unitized Structure)

NASA Technical Reports Server (NTRS)

Horne, Michael R.; Juarez, Peter D.

2016-01-01

In the role of structural health monitoring (SHM), Acoustic Emission (AE) analysis is being investigated as an effective method for tracking damage development in large composite structures under load. Structures made using Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) for damage tolerant, light, and economical airframe construction are being pursued by The Boeing Company and NASA under the Environmentally Responsible Aircraft initiative (ERA). The failure tests of two PRSEUS substructures based on the Boeing Hybrid Wing Body fuselage concept were conducted during third quarter 2011 and second quarter 2015. One fundamental concern of these tests was determining the effectiveness of the stitched integral stiffeners to inhibit damage progression. By design, severe degradation of load carrying capability should not occur prior to Design Ultimate Load (DUL). While minor damage prior to DUL was anticipated, the integral stitching should not fail since this would allow a stiffener-skin delamination to progress rapidly and alter the transfer of load into the stiffeners. In addition, the stiffeners should not fracture because they are fundamental to structural integrity. Getting the best information from each AE sensor is a primary consideration because a sparse network of sensors is implemented. Sensitivity to stiffener-contiguous degradation is supported by sensors near the stiffeners, which increases the coverage per sensor via AE waveguide actions. Some sensors are located near potentially critical areas or "critical zones" as identified by numerical analyses. The approach is compared with the damage progression monitored by other techniques (e.g. ultrasonic C-scan).

The impact of unilateral brain damage on anticipatory grip force scaling when lifting everyday objects.

PubMed

Eidenmüller, S; Randerath, J; Goldenberg, G; Li, Y; Hermsdörfer, J

2014-08-01

The scaling of our finger forces according to the properties of manipulated objects is an elementary prerequisite of skilled motor behavior. Lesions of the motor-dominant left brain may impair several aspects of motor planning. For example, limb-apraxia, a tool-use disorder after left brain damage is thought to be caused by deficient recall or integration of tool-use knowledge into an action plan. The aim of the present study was to investigate whether left brain damage affects anticipatory force scaling when lifting everyday objects. We examined 26 stroke patients with unilateral brain damage (16 with left brain damage, ten with right brain damage) and 21 healthy control subjects. Limb apraxia was assessed by testing pantomime of familiar tool-use and imitation of meaningless hand postures. Participants grasped and lifted twelve randomly presented everyday objects. Grip force was measured with help of sensors fixed on thumb, index and middle-finger. The maximum rate of grip force was determined to quantify the precision of anticipation of object properties. Regression analysis yielded clear deficits of anticipation in the group of patients with left brain damage, while the comparison of patient with right brain damage with their respective control group did not reveal comparable deficits. Lesion-analyses indicate that brain structures typically associated with a tool-use network in the left hemisphere play an essential role for anticipatory grip force scaling, especially the left inferior frontal gyrus (IFG) and the premotor cortex (PMC). Furthermore, significant correlations of impaired anticipation with limb apraxia scores suggest shared representations. However, the presence of dissociations, implicates also independent processes. Overall, our findings suggest that the left hemisphere is engaged in anticipatory grip force scaling for lifting everyday objects. The underlying neural substrate is not restricted to a single region or stream; instead it may rely on the intact functioning of a left hemisphere network that may overlap with the left hemisphere dominant tool-use network. Copyright © 2014 Elsevier Ltd. All rights reserved.

Wireless and real-time structural damage detection: A novel decentralized method for wireless sensor networks

NASA Astrophysics Data System (ADS)

Avci, Onur; Abdeljaber, Osama; Kiranyaz, Serkan; Hussein, Mohammed; Inman, Daniel J.

2018-06-01

Being an alternative to conventional wired sensors, wireless sensor networks (WSNs) are extensively used in Structural Health Monitoring (SHM) applications. Most of the Structural Damage Detection (SDD) approaches available in the SHM literature are centralized as they require transferring data from all sensors within the network to a single processing unit to evaluate the structural condition. These methods are found predominantly feasible for wired SHM systems; however, transmission and synchronization of huge data sets in WSNs has been found to be arduous. As such, the application of centralized methods with WSNs has been a challenge for engineers. In this paper, the authors are presenting a novel application of 1D Convolutional Neural Networks (1D CNNs) on WSNs for SDD purposes. The SDD is successfully performed completely wireless and real-time under ambient conditions. As a result of this, a decentralized damage detection method suitable for wireless SHM systems is proposed. The proposed method is based on 1D CNNs and it involves training an individual 1D CNN for each wireless sensor in the network in a format where each CNN is assigned to process the locally-available data only, eliminating the need for data transmission and synchronization. The proposed damage detection method operates directly on the raw ambient vibration condition signals without any filtering or preprocessing. Moreover, the proposed approach requires minimal computational time and power since 1D CNNs merge both feature extraction and classification tasks into a single learning block. This ability is prevailingly cost-effective and evidently practical in WSNs considering the hardware systems have been occasionally reported to suffer from limited power supply in these networks. To display the capability and verify the success of the proposed method, large-scale experiments conducted on a laboratory structure equipped with a state-of-the-art WSN are reported.

Methodology to improve process understanding of surface runoff causing damages to buildings by analyzing insurance data records

NASA Astrophysics Data System (ADS)

Bernet, Daniel; Prasuhn, Volker; Weingartner, Rolf

2015-04-01

Several case studies in Switzerland highlight that many buildings which are damaged by floods are not located within the inundation zones of rivers, but outside the river network. In urban areas, such flooding can be caused by drainage system surcharge, low infiltration capacity of the urbanized landscape etc. However, in rural and peri-urban areas inundations are more likely caused by surface runoff formed on natural and arable land. Such flash floods have very short response time, occur rather diffusely and, thus, are very difficult to observe directly. In our approach, we use data records from private, but mostly from public insurance companies. The latter, present in 19 out of the total 26 Cantons of Switzerland, insure (almost) every building within the respective administrative zones and, in addition, hold a monopoly position. Damage claims, including flood damages, are usually recorded and, thus, data records from such public insurance companies are a very profitable data source to better understand surface runoff leading to damages. Although practitioners agree that this process is relevant, there seems to be a knowledge gap concerning spatial and temporal distributions as well as triggers and influencing factors of such damage events. Within the framework of a research project, we want to address this research gap and improve the understanding of the process chain from surface runoff formation up to possible damages to buildings. This poster introduces the methodology, which will be applied to a dataset including data from the majority of all 19 public insurance companies for buildings in Switzerland, counting over 50'000 damage claims, in order to better understand surface runoff. The goal is to infer spatial and temporal patterns as well as drivers and influencing factors of surface runoff possibly causing damages. In particular, the workflow of data acquisition, harmonization and treatment is outlined. Furthermore associated problems and challenges are discussed. Ultimately, the improved process understanding will be used to develop a new modeling approach.

Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

PubMed

Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

2016-01-01

The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in promoting survival and the evolution of resistance under antibiotic stress. As a result, targeting the SOS response has been proposed as an adjuvant strategy to revitalize our current antibiotic arsenal. However, the optimal molecular targets and partner antibiotics for such an approach remain unclear. In this study, focusing on the two key regulators of the SOS response, LexA and RecA, we provide the first comprehensive assessment of how to target the SOS response in order to increase bacterial susceptibility and reduce mutagenesis under antibiotic treatment.

Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics

PubMed Central

Mo, Charlie Y.; Manning, Sara A.; Roggiani, Manuela; Culyba, Matthew J.; Samuels, Amanda N.; Sniegowski, Paul D.; Goulian, Mark

2016-01-01

ABSTRACT The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in promoting survival and the evolution of resistance under antibiotic stress. As a result, targeting the SOS response has been proposed as an adjuvant strategy to revitalize our current antibiotic arsenal. However, the optimal molecular targets and partner antibiotics for such an approach remain unclear. In this study, focusing on the two key regulators of the SOS response, LexA and RecA, we provide the first comprehensive assessment of how to target the SOS response in order to increase bacterial susceptibility and reduce mutagenesis under antibiotic treatment. PMID:27536734

Seismic Wavefield Imaging of Long-Period Ground Motion in the Tokyo Metropolitan Area, Japan

NASA Astrophysics Data System (ADS)

Nagao, H.; Kano, M.; Nagata, K.; Ito, S. I.; Sakai, S.; Nakagawa, S.; Hori, M.; Hirata, N.

2017-12-01

Long-period ground motions due to large earthquakes can cause devastating disasters, especially in urbanized areas located on sedimentary basins. To assess and mitigate such damage, it is essential to rapidly evaluate seismic hazards for infrastructures, which can be simulated by seismic response analyses that use waveforms at the base of each infrastructure as an input ground motion. The present study reconstructs the seismic wavefield in the Tokyo metropolitan area located on the Kanto sedimentary basin, Japan, from seismograms of the Metropolitan Seismic Observation network (MeSO-net). The obtained wavefield fully explains the observed waveforms in the frequency band of 0.10-0.20 Hz. This is attributed to the seismic wavefield imaging technique proposed by Kano et al. (2017), which implements the replica exchange Monte Carlo method to simultaneously estimate model parameters related to the subsurface structure and source information. Further investigation shows that the reconstructed seismic wavefield lower than 0.30 Hz is of high quality in terms of variance reduction (VR), which quantifies a misfit in waveforms but that the VR rapidly worsens in higher frequencies. Meanwhile, the velocity response spectra show good agreement with observations up to 0.90 Hz in terms of the combined goodness of fit (CGOF), which is a measure of misfit in the velocity response spectra. Inputting the reconstructed wavefield into seismic response analyses, we can rapidly assess the overall damage to infrastructures immediately after a large earthquake.

Netiquettes for Networkers.

ERIC Educational Resources Information Center

McMurdo, George

1995-01-01

Presents 20 networking etiquette guidelines taken from electronic and print sources. Highlights include focusing on one subject, condensing messages, editing quotes, spelling and grammar, typography, mistakes, acronyms, humor, researching discussion groups, intellectual property and copyright, manners, ethics, and damage. (AEF)

Etude et simulation de la MADA

NASA Astrophysics Data System (ADS)

Defontaines, Remi

Over the past ten years, the production of electric energy using wind turbines has increased eight times. This production of energy is in full expansion, and different means are now at the dispositions of researchers to finally explore it to the maximum. The DFIG is a type of wind turbine that has been the object of numerous studies over the past several years. This wind turbine functions with the speed of the wind. Its principle particularity is that it is constituted of an asynchronous machine, a wound-rotor and is capable of providing active power to the network by the stator and the rotor. This structure permits a good performance over a wide range of wind speeds, at a reasonable cost. It manages to be cost-effective because it uses weakly dimensioned power converters. Despite its advantages, there is a problem: its connection to the network. The electric network is not always stable; it regularly suffers voltage damage (low voltage, unbalance or overvoltage). This damage can result in fault from poor quality in the machine, and this damages or even destroys the power converters. To avoid this issue, the wind turbine disconnects from the network when it undergoes deterioration. The goal of this research is to find a strategy that allows the wind turbine to function even when the network voltage deteriorates, which in turn results in avoiding disconnection and therefore the loss of electrical power.

Use of Savitzky-Golay Filter for Performances Improvement of SHM Systems Based on Neural Networks and Distributed PZT Sensors.

PubMed

de Oliveira, Mario A; Araujo, Nelcileno V S; da Silva, Rodolfo N; da Silva, Tony I; Epaarachchi, Jayantha

2018-01-08

A considerable amount of research has focused on monitoring structural damage using Structural Health Monitoring (SHM) technologies, which has had recent advances. However, it is important to note the challenges and unresolved problems that disqualify currently developed monitoring systems. One of the frontline SHM technologies, the Electromechanical Impedance (EMI) technique, has shown its potential to overcome remaining problems and challenges. Unfortunately, the recently developed neural network algorithms have not shown significant improvements in the accuracy of rate and the required processing time. In order to fill this gap in advanced neural networks used with EMI techniques, this paper proposes an enhanced and reliable strategy for improving the structural damage detection via: (1) Savitzky-Golay (SG) filter, using both first and second derivatives; (2) Probabilistic Neural Network (PNN); and, (3) Simplified Fuzzy ARTMAP Network (SFAN). Those three methods were employed to analyze the EMI data experimentally obtained from an aluminum plate containing three attached PZT (Lead Zirconate Titanate) patches. In this present study, the damage scenarios were simulated by attaching a small metallic nut at three different positions in the aluminum plate. We found that the proposed method achieves a hit rate of more than 83%, which is significantly higher than current state-of-the-art approaches. Furthermore, this approach results in an improvement of 93% when considering the best case scenario.

Use of Savitzky–Golay Filter for Performances Improvement of SHM Systems Based on Neural Networks and Distributed PZT Sensors

PubMed Central

Araujo, Nelcileno V. S.; da Silva, Rodolfo N.; da Silva, Tony I.; Epaarachchi, Jayantha

2018-01-01

A considerable amount of research has focused on monitoring structural damage using Structural Health Monitoring (SHM) technologies, which has had recent advances. However, it is important to note the challenges and unresolved problems that disqualify currently developed monitoring systems. One of the frontline SHM technologies, the Electromechanical Impedance (EMI) technique, has shown its potential to overcome remaining problems and challenges. Unfortunately, the recently developed neural network algorithms have not shown significant improvements in the accuracy of rate and the required processing time. In order to fill this gap in advanced neural networks used with EMI techniques, this paper proposes an enhanced and reliable strategy for improving the structural damage detection via: (1) Savitzky–Golay (SG) filter, using both first and second derivatives; (2) Probabilistic Neural Network (PNN); and, (3) Simplified Fuzzy ARTMAP Network (SFAN). Those three methods were employed to analyze the EMI data experimentally obtained from an aluminum plate containing three attached PZT (Lead Zirconate Titanate) patches. In this present study, the damage scenarios were simulated by attaching a small metallic nut at three different positions in the aluminum plate. We found that the proposed method achieves a hit rate of more than 83%, which is significantly higher than current state-of-the-art approaches. Furthermore, this approach results in an improvement of 93% when considering the best case scenario. PMID:29316693

Influence of the segmentation on the characterization of cerebral networks of structural damage for patients with disorders of consciousness

NASA Astrophysics Data System (ADS)

Martínez, Darwin; Mahalingam, Jamuna J.; Soddu, Andrea; Franco, Hugo; Lepore, Natasha; Laureys, Steven; Gómez, Francisco

2015-01-01

Disorders of consciousness (DOC) are a consequence of a variety of severe brain injuries. DOC commonly results in anatomical brain modifications, which can affect cortical and sub-cortical brain structures. Postmortem studies suggest that severity of brain damage correlates with level of impairment in DOC. In-vivo studies in neuroimaging mainly focus in alterations on single structures. Recent evidence suggests that rather than one, multiple brain regions can be simultaneously affected by this condition. In other words, DOC may be linked to an underlying cerebral network of structural damage. Recently, geometrical spatial relationships among key sub-cortical brain regions, such as left and right thalamus and brain stem, have been used for the characterization of this network. This approach is strongly supported on automatic segmentation processes, which aim to extract regions of interests without human intervention. Nevertheless, patients with DOC usually present massive structural brain changes. Therefore, segmentation methods may highly influence the characterization of the underlying cerebral network structure. In this work, we evaluate the level of characterization obtained by using the spatial relationships as descriptor of a sub-cortical cerebral network (left and right thalamus) in patients with DOC, when different segmentation approaches are used (FSL, Free-surfer and manual segmentation). Our results suggest that segmentation process may play a critical role for the construction of robust and reliable structural characterization of DOC conditions.

How Predictable Are the Behavioral Responses of Insects to Herbivore Induced Changes in Plants? Responses of Two Congeneric Thrips to Induced Cotton Plants

PubMed Central

Silva, Rehan; Furlong, Michael J.; Wilson, Lewis J.; Walter, Gimme H.

2013-01-01

Changes in plants following insect attack are referred to as induced responses. These responses are widely viewed as a form of defence against further insect attack. In the current study we explore whether it is possible to make generalizations about induced plant responses given the unpredictability and variability observed in insect-plant interactions. Experiments were conducted to test for consistency in the responses of two congeneric thrips, Frankliniella schultzei Trybom and Frankliniella occidentalis Pergrande (Thysanoptera: Thripidae) to cotton seedlings (Gossypium hirsutum Linneaus (Malvales: Malvaceae)) damaged by various insect herbivores. In dual-choice experiments that compared intact and damaged cotton seedlings, F. schultzei was attracted to seedlings damaged by Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), Tetranychus urticae (Koch) (Trombidiforms: Tetranychidae), Tenebrio molitor Linnaeus (Coleoptera: Tenebrionidae), F. schultzei and F. occidentalis but not to mechanically damaged seedlings. In similar tests, F. occidentalis was attracted to undamaged cotton seedlings when simultaneously exposed to seedlings damaged by H. armigera, T. molitor or F. occidentalis. However, when exposed to F. schultzei or T. urticae damaged plants, F. occidentalis was more attracted towards damaged plants. A quantitative relationship was also apparent, F. schultzei showed increased attraction to damaged seedlings as the density of T. urticae or F. schultzei increased. In contrast, although F. occidentalis demonstrated increased attraction to plants damaged by higher densities of T. urticae, there was a negative relationship between attraction and the density of damaging conspecifics. Both species showed greater attraction to T. urticae damaged seedlings than to seedlings damaged by conspecifics. Results demonstrate that the responses of both species of thrips were context dependent, making generalizations difficult to formulate. PMID:23691075

TRNA mutations that affect decoding fidelity deregulate development and the proteostasis network in zebrafish

PubMed Central

Reverendo, Marisa; Soares, Ana R; Pereira, Patrícia M; Carreto, Laura; Ferreira, Violeta; Gatti, Evelina; Pierre, Philippe; Moura, Gabriela R; Santos, Manuel A

2014-01-01

Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through proteome instability and saturation of the proteostasis network. To test this hypothesis we have induced mistranslation in zebrafish embryos using mutant tRNAs that misincorporate Serine (Ser) at various non-cognate codon sites. Embryo viability was affected and malformations were observed, but a significant proportion of embryos survived by activating the unfolded protein response (UPR), the ubiquitin proteasome pathway (UPP) and downregulating protein biosynthesis. Accumulation of reactive oxygen species (ROS), mitochondrial and nuclear DNA damage and disruption of the mitochondrial network, were also observed, suggesting that mistranslation had a strong negative impact on protein synthesis rate, ER and mitochondrial homeostasis. We postulate that mistranslation promotes gradual cellular degeneration and disease through protein aggregation, mitochondrial dysfunction and genome instability. PMID:25483040

The Emerging Role of Epigenetics in Stroke

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2013-01-01

The transplantation of exogenous stem cells and the activation of endogenous neural stem and progenitor cells (NSPCs) are promising treatments for stroke. These cells can modulate intrinsic responses to ischemic injury and may even integrate directly into damaged neural networks. However, the neuroprotective and neural regenerative effects that can be mediated by these cells are limited and may even be deleterious. Epigenetic reprogramming represents a novel strategy for enhancing the intrinsic potential of the brain to protect and repair itself by modulating pathologic neural gene expression and promoting the recapitulation of seminal neural developmental processes. In fact, recent evidence suggests that emerging epigenetic mechanisms are critical for orchestrating nearly every aspect of neural development and homeostasis, including brain patterning, neural stem cell maintenance, neurogenesis and gliogenesis, neural subtype specification, and synaptic and neural network connectivity and plasticity. In this review, we survey the therapeutic potential of exogenous stem cells and endogenous NSPCs and highlight innovative technological approaches for designing, developing, and delivering epigenetic therapies for targeted reprogramming of endogenous pools of NSPCs, neural cells at risk, and dysfunctional neural networks to rescue and restore neurologic function in the ischemic brain. PMID:21403016

Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides).

PubMed

Mehinto, Alvine C; Prucha, Melinda S; Colli-Dula, Reyna C; Kroll, Kevin J; Lavelle, Candice M; Barber, David S; Vulpe, Christopher D; Denslow, Nancy D

2014-07-01

Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20μg/kg of cadmium chloride (mean exposure level - 2.6μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly increased in the liver including genes encoding for the rate limiting steroidogenic acute regulatory protein and the catalytic enzyme 7-dehydrocholesterol reductase. Integration of the transcriptomic data using functional enrichment analyses revealed a number of enriched gene networks associated with previously reported adverse outcomes of cadmium exposure such as liver toxicity and impaired reproduction. Copyright © 2014 Elsevier B.V. All rights reserved.

Magnetic Flux Leakage Sensing and Artificial Neural Network Pattern Recognition-Based Automated Damage Detection and Quantification for Wire Rope Non-Destructive Evaluation.

PubMed

Kim, Ju-Won; Park, Seunghee

2018-01-02

In this study, a magnetic flux leakage (MFL) method, known to be a suitable non-destructive evaluation (NDE) method for continuum ferromagnetic structures, was used to detect local damage when inspecting steel wire ropes. To demonstrate the proposed damage detection method through experiments, a multi-channel MFL sensor head was fabricated using a Hall sensor array and magnetic yokes to adapt to the wire rope. To prepare the damaged wire-rope specimens, several different amounts of artificial damages were inflicted on wire ropes. The MFL sensor head was used to scan the damaged specimens to measure the magnetic flux signals. After obtaining the signals, a series of signal processing steps, including the enveloping process based on the Hilbert transform (HT), was performed to better recognize the MFL signals by reducing the unexpected noise. The enveloped signals were then analyzed for objective damage detection by comparing them with a threshold that was established based on the generalized extreme value (GEV) distribution. The detected MFL signals that exceed the threshold were analyzed quantitatively by extracting the magnetic features from the MFL signals. To improve the quantitative analysis, damage indexes based on the relationship between the enveloped MFL signal and the threshold value were also utilized, along with a general damage index for the MFL method. The detected MFL signals for each damage type were quantified by using the proposed damage indexes and the general damage indexes for the MFL method. Finally, an artificial neural network (ANN) based multi-stage pattern recognition method using extracted multi-scale damage indexes was implemented to automatically estimate the severity of the damage. To analyze the reliability of the MFL-based automated wire rope NDE method, the accuracy and reliability were evaluated by comparing the repeatedly estimated damage size and the actual damage size.

Strategic Downsizing and Learning Organisations.

ERIC Educational Resources Information Center

Griggs, Harvey E.; Hyland, Paul

2003-01-01

Downsizing or brain drain may damage the learning capacity of organizations. A case study of an aerospace manufacturing firm shows that appropriate strategies to analyze the impact on formal and informal learning networks may help manage or minimize the damage. (Contains 55 references.) (SK)

The interaction between stress and exercise, and its impact on brain function.

PubMed

Russell, Vivienne A; Zigmond, Michael J; Dimatelis, Jacqueline J; Daniels, William M U; Mabandla, Musa V

2014-06-01

In response to acute adversity, emotional signals shift the body into a state that permits rapid detection, identification, and appropriate response to a potential threat. The stress response involves the release of a variety of substances, including neurotransmitters, neurotrophic factors, hormones, and cytokines, that enable the body to deal with the challenges of daily life. The subsequent activation of various physiological systems can be both protective and damaging to the individual, depending on timing, intensity, and duration of the stressor. Successful recovery from stressful challenges during early life leads to strengthening of synaptic connections in health-promoting neural networks and reduced vulnerability to subsequent stressors that can be protective in later life. In contrast, chronic intense uncontrollable stress can be pathogenic and lead to disorders such as depression, anxiety, hypertension, Alzheimer's disease, Parkinson's disease, and an increased toxic response to additional stressors such as traumatic brain injury and stroke. This review briefly explores the interaction between stress experienced at different stages of development and exercise later in life.

As we age: Does slippage of quality control in the immune system lead to collateral damage?

PubMed

Müller, Ludmila; Pawelec, Graham

2015-09-01

The vertebrate adaptive immune system is remarkable for its possession of a very broad range of antigen receptors imbuing the system with exquisite specificity, in addition to the phagocytic and inflammatory cells of the innate system shared with invertebrates. This system requires strict control both at the level of the generation the cells carrying these receptors and at the level of their activation and effector function mediation in order to avoid autoimmunity and mitigate immune pathology. Thus, quality control checkpoints are built into the system at multiple nodes in the response, relying on clonal selection and regulatory networks to maximize pathogen-directed effects and minimize collateral tissue damage. However, these checkpoints are compromised with age, resulting in poorer immune control manifesting as tissue-damaging autoimmune and inflammatory phenomena which can cause widespread systemic disease, paradoxically compounding the problems associated with increased susceptibility to infectious disease and possibly cancer in the elderly. Better understanding the reasons for slippage of immune control will pave the way for developing rational strategies for interventions to maintain appropriate immunity while reducing immunopathology. Copyright © 2015 Elsevier B.V. All rights reserved.

A Sensor Data Fusion System Based on k-Nearest Neighbor Pattern Classification for Structural Health Monitoring Applications

PubMed Central

Vitola, Jaime; Pozo, Francesc; Tibaduiza, Diego A.; Anaya, Maribel

2017-01-01

Civil and military structures are susceptible and vulnerable to damage due to the environmental and operational conditions. Therefore, the implementation of technology to provide robust solutions in damage identification (by using signals acquired directly from the structure) is a requirement to reduce operational and maintenance costs. In this sense, the use of sensors permanently attached to the structures has demonstrated a great versatility and benefit since the inspection system can be automated. This automation is carried out with signal processing tasks with the aim of a pattern recognition analysis. This work presents the detailed description of a structural health monitoring (SHM) system based on the use of a piezoelectric (PZT) active system. The SHM system includes: (i) the use of a piezoelectric sensor network to excite the structure and collect the measured dynamic response, in several actuation phases; (ii) data organization; (iii) advanced signal processing techniques to define the feature vectors; and finally; (iv) the nearest neighbor algorithm as a machine learning approach to classify different kinds of damage. A description of the experimental setup, the experimental validation and a discussion of the results from two different structures are included and analyzed. PMID:28230796

A Sensor Data Fusion System Based on k-Nearest Neighbor Pattern Classification for Structural Health Monitoring Applications.

PubMed

Vitola, Jaime; Pozo, Francesc; Tibaduiza, Diego A; Anaya, Maribel

2017-02-21

Civil and military structures are susceptible and vulnerable to damage due to the environmental and operational conditions. Therefore, the implementation of technology to provide robust solutions in damage identification (by using signals acquired directly from the structure) is a requirement to reduce operational and maintenance costs. In this sense, the use of sensors permanently attached to the structures has demonstrated a great versatility and benefit since the inspection system can be automated. This automation is carried out with signal processing tasks with the aim of a pattern recognition analysis. This work presents the detailed description of a structural health monitoring (SHM) system based on the use of a piezoelectric (PZT) active system. The SHM system includes: (i) the use of a piezoelectric sensor network to excite the structure and collect the measured dynamic response, in several actuation phases; (ii) data organization; (iii) advanced signal processing techniques to define the feature vectors; and finally; (iv) the nearest neighbor algorithm as a machine learning approach to classify different kinds of damage. A description of the experimental setup, the experimental validation and a discussion of the results from two different structures are included and analyzed.

Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo.

PubMed

Mancuso, M; Pasquali, E; Leonardi, S; Rebessi, S; Tanori, M; Giardullo, P; Borra, F; Pazzaglia, S; Naus, C C; Di Majo, V; Saran, A

2011-11-10

Ionizing radiation is a genotoxic agent and human carcinogen. Recent work has questioned long-held dogmas by showing that cancer-associated genetic alterations occur in cells and tissues not directly exposed to radiation, questioning the robustness of the current system of radiation risk assessment. In vitro, diverse mechanisms involving secreted soluble factors, gap junction intercellular communication (GJIC) and oxidative metabolism are proposed to mediate these indirect effects. In vivo, the mechanisms behind long-range 'bystander' responses remain largely unknown. Here, we investigate the role of GJIC in propagating radiation stress signals in vivo, and in mediating radiation-associated bystander tumorigenesis in mouse central nervous system using a mouse model in which intercellular communication is downregulated by targeted deletion of the connexin43 (Cx43) gene. We show that GJIC is critical for transmission of oncogenic radiation damage to the non-targeted cerebellum, and that a mechanism involving adenosine triphosphate release and upregulation of Cx43, the major GJIC constituent, regulates transduction of oncogenic damage to unirradiated tissues in vivo. Our data provide a novel hypothesis for transduction of distant bystander effects and suggest that the highly branched nervous system, similar to the vascular network, has an important role.

Structural health monitoring using a hybrid network of self-powered accelerometer and strain sensors

NASA Astrophysics Data System (ADS)

Alavi, Amir H.; Hasni, Hassene; Jiao, Pengcheng; Lajnef, Nizar

2017-04-01

This paper presents a structural damage identification approach based on the analysis of the data from a hybrid network of self-powered accelerometer and strain sensors. Numerical and experimental studies are conducted on a plate with bolted connections to verify the method. Piezoelectric ceramic Lead Zirconate Titanate (PZT)-5A ceramic discs and PZT-5H bimorph accelerometers are placed on the surface of the plate to measure the voltage changes due to damage progression. Damage is defined by loosening or removing one bolt at a time from the plate. The results show that the PZT accelerometers provide a fairly more consistent behavior than the PZT strain sensors. While some of the PZT strain sensors are not sensitive to the changes of the boundary condition, the bimorph accelerometers capture the mode changes from undamaged to missing bolt conditions. The results corresponding to the strain sensors are better indicator to the location of damage compared to the accelerometers. The characteristics of the overall structure can be monitored with even one accelerometer. On the other hand, several PZT strain sensors might be needed to localize the damage.

Fear processing and social networking in the absence of a functional amygdala.

PubMed

Becker, Benjamin; Mihov, Yoan; Scheele, Dirk; Kendrick, Keith M; Feinstein, Justin S; Matusch, Andreas; Aydin, Merve; Reich, Harald; Urbach, Horst; Oros-Peusquens, Ana-Maria; Shah, Nadim J; Kunz, Wolfram S; Schlaepfer, Thomas E; Zilles, Karl; Maier, Wolfgang; Hurlemann, René

2012-07-01

The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing. To investigate the brain's functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease. Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule. The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Detection of Oil Chestnuts Infected by Blue Mold Using Near-Infrared Hyperspectral Imaging Combined with Artificial Neural Networks.

PubMed

Feng, Lei; Zhu, Susu; Lin, Fucheng; Su, Zhenzhu; Yuan, Kangpei; Zhao, Yiying; He, Yong; Zhang, Chu

2018-06-15

Mildew damage is a major reason for chestnut poor quality and yield loss. In this study, a near-infrared hyperspectral imaging system in the 874⁻1734 nm spectral range was applied to detect the mildew damage to chestnuts caused by blue mold. Principal component analysis (PCA) scored images were firstly employed to qualitatively and intuitively distinguish moldy chestnuts from healthy chestnuts. Spectral data were extracted from the hyperspectral images. A successive projections algorithm (SPA) was used to select 12 optimal wavelengths. Artificial neural networks, including back propagation neural network (BPNN), evolutionary neural network (ENN), extreme learning machine (ELM), general regression neural network (GRNN) and radial basis neural network (RBNN) were used to build models using the full spectra and optimal wavelengths to distinguish moldy chestnuts. BPNN and ENN models using full spectra and optimal wavelengths obtained satisfactory performances, with classification accuracies all surpassing 99%. The results indicate the potential for the rapid and non-destructive detection of moldy chestnuts by hyperspectral imaging, which would help to develop online detection system for healthy and blue mold infected chestnuts.

Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress

PubMed Central

McDade, Simon S.; Patel, Daksha; Moran, Michael; Campbell, James; Fenwick, Kerry; Kozarewa, Iwanka; Orr, Nicholas J.; Lord, Christopher J.; Ashworth, Alan A.; McCance, Dennis J.

2014-01-01

In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome-wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53-dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveal that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair. PMID:24823795

Targeting Protein Quality Control Mechanisms by Natural Products to Promote Healthy Ageing.

PubMed

Wedel, Sophia; Manola, Maria; Cavinato, Maria; Trougakos, Ioannis P; Jansen-Dürr, Pidder

2018-05-19

Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due to the time-dependent decline of stress resistance and functional capacity, which eventually compromise cellular homeodynamics. As protein machines carry out the majority of cellular functions, proteome quality control is critical for cellular functionality and is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the two main degradation machineries, namely the ubiquitin-proteasome and autophagy-lysosome pathways along with several stress-responsive pathways, such as that of nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises cytoprotective genomic responses against oxidative and/or xenobiotic damage. Reportedly, genetic or dietary interventions that activate components of the PN delay ageing in evolutionarily diverse organisms. Natural products (extracts or pure compounds) represent an extraordinary inventory of highly diverse structural scaffolds that offer promising activities towards meeting the challenge of increasing healthspan and/or delaying ageing (e.g., spermidine, quercetin or sulforaphane). Herein, we review those natural compounds that have been found to activate proteostatic and/or anti-stress cellular responses and hence have the potential to delay cellular senescence and/or in vivo ageing.

A proposal for a separative network to evacuate drainage waters and pluvial waters of stagnation in arid zones (Ain Sahra locality, Touggourt, Algeria)

NASA Astrophysics Data System (ADS)

Nettari, Kamel; Boutoutaou, Djamel; Rezagui, Djihed

2018-05-01

Many agglomerations of the Algerian Sahara, are currently affected by a rise of waters of the superficial aquifer. This rise is due to discharges of drainage water and urban wastewater. In addition, the rare stormy rains that occur in these areas cause very high material damage. To avoid this damage, it is essential to propose a separative network to evacuate the drainage andpluvial stagnant waters and propose some adequate solutions to avoid potential flooding.

Epigenetic Telomere Protection by Drosophila DNA Damage Response Pathways

PubMed Central

Oikemus, Sarah R; Queiroz-Machado, Joana; Lai, KuanJu; McGinnis, Nadine; Sunkel, Claudio; Brodsky, Michael H

2006-01-01

Analysis of terminal deletion chromosomes indicates that a sequence-independent mechanism regulates protection of Drosophila telomeres. Mutations in Drosophila DNA damage response genes such as atm/tefu, mre11, or rad50 disrupt telomere protection and localization of the telomere-associated proteins HP1 and HOAP, suggesting that recognition of chromosome ends contributes to telomere protection. However, the partial telomere protection phenotype of these mutations limits the ability to test if they act in the epigenetic telomere protection mechanism. We examined the roles of the Drosophila atm and atr-atrip DNA damage response pathways and the nbs homolog in DNA damage responses and telomere protection. As in other organisms, the atm and atr-atrip pathways act in parallel to promote telomere protection. Cells lacking both pathways exhibit severe defects in telomere protection and fail to localize the protection protein HOAP to telomeres. Drosophila nbs is required for both atm- and atr-dependent DNA damage responses and acts in these pathways during DNA repair. The telomere fusion phenotype of nbs is consistent with defects in each of these activities. Cells defective in both the atm and atr pathways were used to examine if DNA damage response pathways regulate telomere protection without affecting telomere specific sequences. In these cells, chromosome fusion sites retain telomere-specific sequences, demonstrating that loss of these sequences is not responsible for loss of protection. Furthermore, terminally deleted chromosomes also fuse in these cells, directly implicating DNA damage response pathways in the epigenetic protection of telomeres. We propose that recognition of chromosome ends and recruitment of HP1 and HOAP by DNA damage response proteins is essential for the epigenetic protection of Drosophila telomeres. Given the conserved roles of DNA damage response proteins in telomere function, related mechanisms may act at the telomeres of other organisms. PMID:16710445

Epigenetic telomere protection by Drosophila DNA damage response pathways.

PubMed

Oikemus, Sarah R; Queiroz-Machado, Joana; Lai, KuanJu; McGinnis, Nadine; Sunkel, Claudio; Brodsky, Michael H

2006-05-01

Analysis of terminal deletion chromosomes indicates that a sequence-independent mechanism regulates protection of Drosophila telomeres. Mutations in Drosophila DNA damage response genes such as atm/tefu, mre11, or rad50 disrupt telomere protection and localization of the telomere-associated proteins HP1 and HOAP, suggesting that recognition of chromosome ends contributes to telomere protection. However, the partial telomere protection phenotype of these mutations limits the ability to test if they act in the epigenetic telomere protection mechanism. We examined the roles of the Drosophila atm and atr-atrip DNA damage response pathways and the nbs homolog in DNA damage responses and telomere protection. As in other organisms, the atm and atr-atrip pathways act in parallel to promote telomere protection. Cells lacking both pathways exhibit severe defects in telomere protection and fail to localize the protection protein HOAP to telomeres. Drosophila nbs is required for both atm- and atr-dependent DNA damage responses and acts in these pathways during DNA repair. The telomere fusion phenotype of nbs is consistent with defects in each of these activities. Cells defective in both the atm and atr pathways were used to examine if DNA damage response pathways regulate telomere protection without affecting telomere specific sequences. In these cells, chromosome fusion sites retain telomere-specific sequences, demonstrating that loss of these sequences is not responsible for loss of protection. Furthermore, terminally deleted chromosomes also fuse in these cells, directly implicating DNA damage response pathways in the epigenetic protection of telomeres. We propose that recognition of chromosome ends and recruitment of HP1 and HOAP by DNA damage response proteins is essential for the epigenetic protection of Drosophila telomeres. Given the conserved roles of DNA damage response proteins in telomere function, related mechanisms may act at the telomeres of other organisms.

International postseismic response after the Mw=7.8 April 16, 2016 Pedernales Earthquake in Ecuador

NASA Astrophysics Data System (ADS)

Font, Y.; Ruiz, M. C.; Alvarado, A. P.; Mercerat, D.; Beck, S. L.; Leon Rios, S.; Meltzer, A.; Charvis, P.; Regnier, M. M.; Jarrin, P.; Rietbrock, A.; Vasconez, F.; Dionicio, V.; Calvache, M. L.; Singaucho, J. C.; Pazmino, A.; Rolandone, F.; Mothes, P. A.; Nocquet, J. M.; Martin, X.; Viracucha, C.; Audin, L.; Saillard, M.; Laurendeau, A.; Perrault, M.; Garth, T.; Pernoud, M.; Barros, J. G.; Yates, B.; Malengros, D.; Oregioni, D.; Villegas Lanza, J. C.; Cisneros, D.; Gomez, J.; Montes, L.; Beauval, C. M.; Bertrand, E.; Delouis, B.; Ruiz Paspuel, A. G.; Freymueller, J. T.; Williams, K.; La Femina, P.; Fuenzalida, A.; Mariniere, J.; Cheze, J.; Gueguen, P.; Maron, C.; Michaud, F.; Yepes, H. A.; Palacios, P.; Vallee, M.; Deschamps, A.; Gabriela, P.; Ambrois, D.; Ramos, C.; Courboulex, F.

2016-12-01

The Pedernales earthquake is a large Mw7.8 subduction earthquake caused by the relative convergence between the Nazca and South American plates. It occured north of the city of Pedernales, at 21 km depth and struck the coastal and densely populated Manabi Province, causing many casualties, structural damages and widespread surficial deformation. The 2016 epicenter was located near the Mw 7.8 1942 epicenter. Both events are similar in size and probably ruptured the same segment, which also corresponds to the southern part of the 1906 Mw8.8 Ecuador-Colombia megathrust rupture zone. Immediately after the earthquake, an international team from Ecuador, France, Colombia, the United Kingdom, Peru and the United States coordinated a scientific response with the respective financial support of EPN, IRD and CNRS, SGC, NERC and NSF. Equipment was provided by IGEPN, IRD, CEREMA, SGC, LIVERPOOL, IRIS PASSCAL and UNAVCO. Within a 1.5 month, the team progressively deployed a temporary seismic network of about 70 accelerometer and seismic stations, and 17 continuous GPS stations, complementing the permanent seismic, accelerometer and geodetic network of the IG-EPN. The dense network covers the 300 x 150 km wide area affected by the earthquake, including a trench-parallel line of 10 ocean bottom seismometers deployed by the R/V Orion of INOCAR for 6 months, assuring a minimized azimuthal gap. Intense seismicity is observed up to 150 km N- and S-ward from the rupture zone aligning mainly along 3 seismic strips roughly perpendicular to the trench and also near the rupture area. Peak ground and spectral accelerations are compared with existing ground-motion prediction equations (GMPEs) developed for interface earthquakes. Different soil investigations were realized to highlight soil characteristics in cities. The geodetic observations captured the immediate afterslip and will help determining the time history of afterslip and viscoelastic relaxation in response to this earthquake. A field survey was conducted on-land to describe the coseismic tectonic deformations and damages to buildings. At sea, a multibeam bathymetry survey of the margin over the rupture zone was conducted by the R/V Orion, making it possible to tentatively estimate and quantify sea-floor deformation after and before the earthquake.

Structural Health Monitoring of a Composite Panel Based on PZT Sensors and a Transfer Impedance Framework

PubMed Central

Dziendzikowski, Michal; Niedbala, Patryk; Kurnyta, Artur; Kowalczyk, Kamil; Dragan, Krzysztof

2018-01-01

One of the ideas for development of Structural Health Monitoring (SHM) systems is based on excitation of elastic waves by a network of PZT piezoelectric transducers integrated with the structure. In the paper, a variant of the so-called Transfer Impedance (TI) approach to SHM is followed. Signal characteristics, called the Damage Indices (DIs), were proposed for data presentation and analysis. The idea underlying the definition of DIs was to maintain most of the information carried by the voltage induced on PZT sensors by elastic waves. In particular, the DIs proposed in the paper should be sensitive to all types of damage which can influence the amplitude or the phase of the voltage induced on the sensor. Properties of the proposed DIs were investigated experimentally using a GFRP composite panel equipped with PZT networks attached to its surface and embedded into its internal structure. Repeatability and stability of DI indications under controlled conditions were verified in tests. Also, some performance indicators for surface-attached and structure-embedded sensors were obtained. The DIs’ behavior was dependent mostly on the presence of a simulated damage in the structure. Anisotropy of mechanical properties of the specimen, geometrical properties of PZT network as well as, to some extent, the technology of sensor integration with the structure were irrelevant for damage indication. This property enables the method to be used for damage detection and classification. PMID:29751664

A novel transcription factor gene FHS1 is involved in the DNA damage response in Fusarium graminearum

PubMed Central

Son, Hokyoung; Fu, Minmin; Lee, Yoonji; Lim, Jae Yun; Min, Kyunghun; Kim, Jin-Cheol; Choi, Gyung Ja; Lee, Yin-Won

2016-01-01

Cell cycle regulation and the maintenance of genome integrity are crucial for the development and virulence of the pathogenic plant fungus Fusarium graminearum. To identify transcription factors (TFs) related to these processes, four DNA-damaging agents were applied to screen a F. graminearum TF mutant library. Sixteen TFs were identified to be likely involved in DNA damage responses. Fhs1 is a fungal specific Zn(II)2Cys6 TF that localises exclusively to nuclei. fhs1 deletion mutants were hypersensitive to hydroxyurea and defective in mitotic cell division. Moreover, deletion of FHS1 resulted in defects in perithecia production and virulence and led to the accumulation of DNA damage. Our genetic evidence demonstrated that the FHS1-associated signalling pathway for DNA damage response is independent of the ATM or ATR pathways. This study identified sixteen genes involved in the DNA damage response and is the first to characterise the novel transcription factor gene FHS1, which is involved in the DNA damage response. The results provide new insights into mechanisms underlying DNA damage responses in fungi, including F. graminearum. PMID:26888604

Pore network properties of sandstones in a fault damage zone

NASA Astrophysics Data System (ADS)

Bossennec, Claire; Géraud, Yves; Moretti, Isabelle; Mattioni, Luca; Stemmelen, Didier

2018-05-01

The understanding of fluid flow in faulted sandstones is based on a wide range of techniques. These depend on the multi-method determination of petrological and structural features, porous network properties and both spatial and temporal variations and interactions of these features. The question of the multi-parameter analysis on fluid flow controlling properties is addressed for an outcrop damage zone in the hanging wall of a normal fault zone on the western border of the Upper Rhine Graben, affecting the Buntsandstein Group (Early Triassic). Diagenetic processes may alter the original pore type and geometry in fractured and faulted sandstones. Therefore, these may control the ultimate porosity and permeability of the damage zone. The classical model of evolution of hydraulic properties with distance from the major fault core is nuanced here. The hydraulic behavior of the rock media is better described by a pluri-scale model including: 1) The grain scale, where the hydraulic properties are controlled by sedimentary features, the distance from the fracture, and the impact of diagenetic processes. These result in the ultimate porous network characteristics observed. 2) A larger scale, where the structural position and characteristics (density, connectivity) of the fracture corridors are strongly correlated with both geo-mechanical and hydraulic properties within the damage zone.

Modelling multi-hazard hurricane damages on an urbanized coast with a Bayesian Network approach

USGS Publications Warehouse

van Verseveld, H.C.W.; Van Dongeren, A. R.; Plant, Nathaniel G.; Jäger, W.S.; den Heijer, C.

2015-01-01

Hurricane flood impacts to residential buildings in coastal zones are caused by a number of hazards, such as inundation, overflow currents, erosion, and wave attack. However, traditional hurricane damage models typically make use of stage-damage functions, where the stage is related to flooding depth only. Moreover, these models are deterministic and do not consider the large amount of uncertainty associated with both the processes themselves and with the predictions. This uncertainty becomes increasingly important when multiple hazards (flooding, wave attack, erosion, etc.) are considered simultaneously. This paper focusses on establishing relationships between observed damage and multiple hazard indicators in order to make better probabilistic predictions. The concept consists of (1) determining Local Hazard Indicators (LHIs) from a hindcasted storm with use of a nearshore morphodynamic model, XBeach, and (2) coupling these LHIs and building characteristics to the observed damages. We chose a Bayesian Network approach in order to make this coupling and used the LHIs ‘Inundation depth’, ‘Flow velocity’, ‘Wave attack’, and ‘Scour depth’ to represent flooding, current, wave impacts, and erosion related hazards.The coupled hazard model was tested against four thousand damage observations from a case site at the Rockaway Peninsula, NY, that was impacted by Hurricane Sandy in late October, 2012. The model was able to accurately distinguish ‘Minor damage’ from all other outcomes 95% of the time and could distinguish areas that were affected by the storm, but not severely damaged, 68% of the time. For the most heavily damaged buildings (‘Major Damage’ and ‘Destroyed’), projections of the expected damage underestimated the observed damage. The model demonstrated that including multiple hazards doubled the prediction skill, with Log-Likelihood Ratio test (a measure of improved accuracy and reduction in uncertainty) scores between 0.02 and 0.17 when only one hazard is considered and a score of 0.37 when multiple hazards are considered simultaneously. The LHIs with the most predictive skill were ‘Inundation depth’ and ‘Wave attack’. The Bayesian Network approach has several advantages over the market-standard stage-damage functions: the predictive capacity of multiple indicators can be combined; probabilistic predictions can be obtained, which include uncertainty; and quantitative as well as descriptive information can be used simultaneously.

The genetic interaction network of CCW12, a Saccharomyces cerevisiae gene required for cell wall integrity during budding and formation of mating projections

PubMed Central

2011-01-01

Background Mannoproteins construct the outer cover of the fungal cell wall. The covalently linked cell wall protein Ccw12p is an abundant mannoprotein. It is considered as crucial structural cell wall component since in baker's yeast the lack of CCW12 results in severe cell wall damage and reduced mating efficiency. Results In order to explore the function of CCW12, we performed a Synthetic Genetic Analysis (SGA) and identified genes that are essential in the absence of CCW12. The resulting interaction network identified 21 genes involved in cell wall integrity, chitin synthesis, cell polarity, vesicular transport and endocytosis. Among those are PFD1, WHI3, SRN2, PAC10, FEN1 and YDR417C, which have not been related to cell wall integrity before. We correlated our results with genetic interaction networks of genes involved in glucan and chitin synthesis. A core of genes essential to maintain cell integrity in response to cell wall stress was identified. In addition, we performed a large-scale transcriptional analysis and compared the transcriptional changes observed in mutant ccw12Δ with transcriptomes from studies investigating responses to constitutive or acute cell wall damage. We identified a set of genes that are highly induced in the majority of the mutants/conditions and are directly related to the cell wall integrity pathway and cell wall compensatory responses. Among those are BCK1, CHS3, EDE1, PFD1, SLT2 and SLA1 that were also identified in the SGA. In contrast, a specific feature of mutant ccw12Δ is the transcriptional repression of genes involved in mating. Physiological experiments substantiate this finding. Further, we demonstrate that Ccw12p is present at the cell periphery and highly concentrated at the presumptive budding site, around the bud, at the septum and at the tip of the mating projection. Conclusions The combination of high throughput screenings, phenotypic analyses and localization studies provides new insight into the function of Ccw12p. A compensatory response, culminating in cell wall remodelling and transport/recycling pathways is required to buffer the loss of CCW12. Moreover, the enrichment of Ccw12p in bud, septum and mating projection is consistent with a role of Ccw12p in preserving cell wall integrity at sites of active growth. The microarray data produced in this analysis have been submitted to NCBI GEO database and GSE22649 record was assigned. PMID:21320323

Seismic Monitoring for the United Arab Emirates

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

Rodgers, A; Nakanishi, K

2005-04-11

There is potential for earthquakes in the United Arab Emirates and in the Zagros mountains to cause structural damage and pose a threat to safety of people. Damaging effects from earthquakes can be mitigated by knowledge of the location and size of earthquakes, effects on construction, and monitoring these effects over time. Although a general idea of seismicity in the UAE may be determined with data from global seismic networks, these global networks do not have the sensitivity to record smaller seismic events and do not have the necessary accuracy to locate the events. A National Seismic Monitoring Observatory ismore » needed for the UAE that consists of a modern seismic network and a multidisciplinary staff that can analyze and interpret the data from the network. A seismic network is essential to locate earthquakes, determine event magnitudes, identify active faults and measure ground motions from earthquakes. Such a network can provide the data necessary for a reliable seismic hazard assessment in the UAE. The National Seismic Monitoring Observatory would ideally be situated at a university that would provide access to the wide range of disciplines needed in operating the network and providing expertise in analysis and interpretation.« less

Estimating the residual axial load capacity of flexure-dominated reinforced concrete bridge columns.

DOT National Transportation Integrated Search

2014-08-01

Extreme events such as earthquakes have the potential to damage hundreds, if not thousands, of bridges on a : transportation network. Following an earthquake, the damaged bridges are inspected by engineers sequentially to : decide whether or not to c...

Integrated Fatigue Damage Diagnosis and Prognosis Under Uncertainties

DTIC Science & Technology

2012-09-01

Integrated fatigue damage diagnosis and prognosis under uncertainties Tishun Peng 1 , Jingjing He 1 , Yongming Liu 1 , Abhinav Saxena 2 , Jose...Ames Research Center, Moffett Field, CA, 94035, USA kai.goebel@nasa.gov ABSTRACT An integrated fatigue damage diagnosis and prognosis framework is...remaining useful life (RUL) prediction. First, a piezoelectric sensor network is used to detect the fatigue crack size near the rivet holes in fuselage

Experimental validation of a structural damage detection method based on marginal Hilbert spectrum

NASA Astrophysics Data System (ADS)

Banerji, Srishti; Roy, Timir B.; Sabamehr, Ardalan; Bagchi, Ashutosh

2017-04-01

Structural Health Monitoring (SHM) using dynamic characteristics of structures is crucial for early damage detection. Damage detection can be performed by capturing and assessing structural responses. Instrumented structures are monitored by analyzing the responses recorded by deployed sensors in the form of signals. Signal processing is an important tool for the processing of the collected data to diagnose anomalies in structural behavior. The vibration signature of the structure varies with damage. In order to attain effective damage detection, preservation of non-linear and non-stationary features of real structural responses is important. Decomposition of the signals into Intrinsic Mode Functions (IMF) by Empirical Mode Decomposition (EMD) and application of Hilbert-Huang Transform (HHT) addresses the time-varying instantaneous properties of the structural response. The energy distribution among different vibration modes of the intact and damaged structure depicted by Marginal Hilbert Spectrum (MHS) detects location and severity of the damage. The present work investigates damage detection analytically and experimentally by employing MHS. The testing of this methodology for different damage scenarios of a frame structure resulted in its accurate damage identification. The sensitivity of Hilbert Spectral Analysis (HSA) is assessed with varying frequencies and damage locations by means of calculating Damage Indices (DI) from the Hilbert spectrum curves of the undamaged and damaged structures.

Modulation of inflammation and disease tolerance by DNA damage response pathways.

PubMed

Neves-Costa, Ana; Moita, Luis F

2017-03-01

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock. © 2016 Federation of European Biochemical Societies.

Dynamics and Adaptive Control for Stability Recovery of Damaged Aircraft

NASA Technical Reports Server (NTRS)

Nguyen, Nhan; Krishnakumar, Kalmanje; Kaneshige, John; Nespeca, Pascal

2006-01-01

This paper presents a recent study of a damaged generic transport model as part of a NASA research project to investigate adaptive control methods for stability recovery of damaged aircraft operating in off-nominal flight conditions under damage and or failures. Aerodynamic modeling of damage effects is performed using an aerodynamic code to assess changes in the stability and control derivatives of a generic transport aircraft. Certain types of damage such as damage to one of the wings or horizontal stabilizers can cause the aircraft to become asymmetric, thus resulting in a coupling between the longitudinal and lateral motions. Flight dynamics for a general asymmetric aircraft is derived to account for changes in the center of gravity that can compromise the stability of the damaged aircraft. An iterative trim analysis for the translational motion is developed to refine the trim procedure by accounting for the effects of the control surface deflection. A hybrid direct-indirect neural network, adaptive flight control is proposed as an adaptive law for stabilizing the rotational motion of the damaged aircraft. The indirect adaptation is designed to estimate the plant dynamics of the damaged aircraft in conjunction with the direct adaptation that computes the control augmentation. Two approaches are presented 1) an adaptive law derived from the Lyapunov stability theory to ensure that the signals are bounded, and 2) a recursive least-square method for parameter identification. A hardware-in-the-loop simulation is conducted and demonstrates the effectiveness of the direct neural network adaptive flight control in the stability recovery of the damaged aircraft. A preliminary simulation of the hybrid adaptive flight control has been performed and initial data have shown the effectiveness of the proposed hybrid approach. Future work will include further investigations and high-fidelity simulations of the proposed hybrid adaptive Bight control approach.

Injury and immune response: applying the danger theory to mosquitoes

PubMed Central

Moreno-García, Miguel; Recio-Tótoro, Benito; Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

2014-01-01

The insect immune response can be activated by the recognition of both non-self and molecular by-products of tissue damage. Since pathogens and tissue damage usually arise at the same time during infection, the specific mechanisms of the immune response to microorganisms, and to tissue damage have not been unraveled. Consequently, some aspects of damage caused by microorganisms in vector-borne arthropods have been neglected. We herein reassess the Anopheles–Plasmodium interaction, incorporating Matzinger’s danger/damage hypothesis and George Salt’s injury assumptions. The invasive forms of the parasite cross the peritrophic matrix and midgut epithelia to reach the basal lamina and differentiate into an oocyst. The sporozoites produced in the oocyst are released into the hemolymph, and from there enter the salivary gland. During parasite development, wounds to midgut tissue and the basement membrane are produced. We describe the response of the different compartments where the parasite interacts with the mosquito. In the midgut, the response includes the expression of antimicrobial peptides, production of reactive oxygen species, and possible activation of midgut regenerative cells. In the basal membrane, wound repair mainly involves the production of molecules and the recruitment of hemocytes. We discuss the susceptibility to damage in tissues, and how the place and degree of damage may influence the differential response and the expression of damage associated molecular patterns (DAMPs). Knowledge about damage caused by parasites may lead to a deeper understanding of the relevance of tissue damage and the immune response it generates, as well as the origins and progression of infection in this insect–parasite interaction. PMID:25250040

Networks in disasters: Multidisciplinary communication and coordination in response and recovery to the 2010 Haiti Earthquake (Invited)

NASA Astrophysics Data System (ADS)

McAdoo, B. G.; Augenstein, J.; Comfort, L.; Huggins, L.; Krenitsky, N.; Scheinert, S.; Serrant, T.; Siciliano, M.; Stebbins, S.; Sweeney, P.; University Of Pittsburgh Haiti Reconnaissance Team

2010-12-01

The 12 January 2010 earthquake in Haiti demonstrates the necessity of understanding information communication between disciplines during disasters. Armed with data from a variety of sources, from geophysics to construction, water and sanitation to education, decision makers can initiate well-informed policies to reduce the risk from future hazards. At the core of this disaster was a natural hazard that occurred in an environmentally compromised country. The earthquake itself was not solely responsible for the magnitude of the disaster- poor construction practices precipitated by extreme poverty, a two centuries of post-colonial environmental degradation and a history of dysfunctional government shoulder much of the responsibility. Future policies must take into account the geophysical reality that future hazards are inevitable and may occur within the very near future, and how various institutions will respond to the stressors. As the global community comes together in reconstruction efforts, it is necessary for the various actors to take into account what vulnerabilities were exposed by the earthquake, most vividly seen during the initial response to the disaster. Responders are forced to prioritize resources designated for building collapse and infrastructure damage, delivery of critical services such as emergency medical care, and delivery of food and water to those in need. Past disasters have shown that communication lapses between the response and recovery phases results in many of the exposed vulnerabilities not being adequately addressed, and the recovery hence fails to bolster compromised systems. The response reflects the basic characteristics of a Complex Adaptive System, where new agents emerge and priorities within existing organizations shift to deal with new information. To better understand how information is shared between actors during this critical transition, we are documenting how information is communicated between critical sectors during the response and recovery phases. Our team consists of experts in natural hazards, public health, shelter and infrastructure, education, and security. We are performing a network analysis based on the content of news and situation reports in media and from UN and aid agencies, field reports by academics and organizations like EERI, and discussions with agencies in Haiti. During three trips to Haiti, we have documented what information was being collected by key stakeholders including government, United Nations, non-governmental organizations, and both domestic and international educational institutions. Insights gained from this analysis of disaster response and recovery operations are invaluable in informing the next state of risk reduction, the transition to a sustainable recovery in a damaged region.

The Effects of Intraspinal Microstimulation on Spinal Cord Tissue in the Rat

PubMed Central

Bamford, Jeremy A.; Todd, Kathryn G.; Mushahwar, Vivian K.

2010-01-01

Intraspinal microstimulation (ISMS) involves the implantation of microwires into the spinal cord below the level of an injury to excite neural networks involved in the control of locomotion in the lower limbs. The goal of this study was to examine the potential spinal cord damage that might occur with chronic ISMS. We employed functional measures of force recruitment and immunohistochemical processing of serial spinal cord sections to evaluate any damage induced by spinal transection, implantation of ISMS arrays, and electrical stimulation of 4 hours/day for 30 days. Functional measurements showed no change in force recruitment following transection and chronic ISMS, indicating no changes to underlying neural networks. The implantation of sham intraspinal microwires produced a spatially-limited increase in the density of microglia/macrophages and GFAP+ astrocytes adjacent to the microwire tracks, indicating a persistent immune response. Most importantly, these results were not different from those around microwires that were chronically pulsed with charge levels up to 48 nC/phase. Likewise, measurements of neuronal density indicated no decrease in neuronal cell bodies in the ventral grey matter surrounding ISMS microwires (243.6/mm2 ± 35.3/mm2) compared to tissue surrounding sham microwires (207.8/mm2 ± 38.8/mm2). We conclude that the implantation of intraspinal microwires and chronic application of ISMS are well tolerated by spinal cord tissue. PMID:20430436

Smart pipeline network : pipe and repair sensor system.

DOT National Transportation Integrated Search

2013-07-26

Leak detection within the national pipeline network has long been recognized as a much-needed : capability to reduce the loss of high value product, improve public safety, and to reduce the : emissions of environmentally damaging substances. : In rec...

Testing GIC Mitigation Protocols by Modelling Transformer-Level GIC Flow in New Zealand's Electrical Transmission Grid

NASA Astrophysics Data System (ADS)

Divett, T.; Ingham, M.; Rodger, C. J.; Richardson, G. S.; Beggan, C.; Thomson, A. W. P.; Dalzell, M.; Mac Manus, D. H.

2017-12-01

Transformers in the South Island of Transpower New Zealand Ltd's electrical transmission network have been impacted by geomagnetically induced currents (GIC) during geomagnetic storms, including the November 2001 event. We aim to make recommendations that lead to improving mitigation strategies for reducing these impacts during extreme events. We have adapted a thin-sheet electromagnetic and GIC network modelling approach that has previously been successfully used in the UK to New Zealand's geology and transmission network. In this presentation we show how we have used this approach to explore Transpower's mitigation procedure as well as alternative mitigation options for reducing the impact of space weather on the network. In order to compare modelled GIC with what has been described as `possibly the best GIC dataset in the world' (Boteler and Pirjola, Pers. Comm. 2016) our model includes every transformer and every high voltage transmission line in the South Island network. This level of detail was required to match the transformer level observations of GIC in the network and to appropriately assess the mitigation options at the level where the damage to power networks occurs. We found that removing a single generator at a central power station and four transmission lines is enough to effectively redistribute GIC away from transformers that have previously experienced very high GIC (as shown in Figure). The redistributed GIC is less damaging to the transformers that it is redistributed to due to lower total GIC at those locations. In the past the impact of GIC on transformers has occurred in the first two minutes of a storm. Hence, mitigation strategies that currently rely on human intervention and involving delays of up to 15 minutes may need to be initiated very rapidly, in a significant departure from Transpower's existing protocol. Reducing delays should significantly reduce the potential for damage in a storm equivalent to the 2001 event. During an extreme storm we expect GIC of 300 A or more to flow through multiple transformers across both islands. In the case of an extreme storm we suggest the more drastic approach of floating the entire network to reduce the potential for damage while retaining power supply to the majority of the country.

Characterization of Aircraft Structural Damage Using Guided Wave Based Finite Element Analysis for In-Flight Structural Health Management

NASA Technical Reports Server (NTRS)

Seshadri, Banavara R.; Krishnamurthy, Thiagarajan; Ross, Richard W.

2016-01-01

The development of multidisciplinary Integrated Vehicle Health Management (IVHM) tools will enable accurate detection, diagnosis and prognosis of damage under normal and adverse conditions during flight. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable catastrophic propagation of damage during a flight, load levels must be maintained that are below the load-carrying capacity for damaged aircraft structures. Hence, a capability is needed for accurate real-time predictions of safe load carrying capacity for aircraft structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size and location is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size and location is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries and sizes.

Cross-Layer Damage Assessment for Cyber Situational Awareness

NASA Astrophysics Data System (ADS)

Liu, Peng; Jia, Xiaoqi; Zhang, Shengzhi; Xiong, Xi; Jhi, Yoon-Chan; Bai, Kun; Li, Jason

Damage assessment plays a very important role in securing enterprise networks and systems. Gaining good awareness about the effects and impact of cyber attack actions would enable security officers to make the right cyber defense decisions and take the right cyber defense actions. A good number of damage assessment techniques have been proposed in the literature, but they typically focus on a single abstraction level (of the software system in concern). As a result, existing damage assessment techniques and tools are still very limited in satisfying the needs of comprehensive damage assessment which should not result in any “blind spots”.

Proposed health state awareness of helicopter blades using an artificial neural network strategy

NASA Astrophysics Data System (ADS)

Lee, Andrew; Habtour, Ed; Gadsden, S. A.

2016-05-01

Structural health prognostics and diagnosis strategies can be classified as either model or signal-based. Artificial neural network strategies are popular signal-based techniques. This paper proposes the use of helicopter blades in order to study the sensitivity of an artificial neural network to structural fatigue. The experimental setup consists of a scale aluminum helicopter blade exposed to transverse vibratory excitation at the hub using single axis electrodynamic shaker. The intent of this study is to optimize an algorithm for processing high-dimensional data while retaining important information content in an effort to select input features and weights, as well as health parameters, for training a neural network. Data from accelerometers and piezoelectric transducers is collected from a known system designated as healthy. Structural damage will be introduced to different blades, which they will be designated as unhealthy. A variety of different tests will be performed to track the evolution and severity of the damage. A number of damage detection and diagnosis strategies will be implemented. A preliminary experiment was performed on aluminum cantilever beams providing a simpler model for implementation and proof of concept. Future work will look at utilizing the detection information as part of a hierarchical control system in order to mitigate structural damage and fatigue. The proposed approach may eliminate massive data storage on board of an aircraft through retaining relevant information only. The control system can then employ the relevant information to intelligently reconfigure adaptive maneuvers to avoid harmful regimes, thus, extending the life of the aircraft.

Neural Networks for Flight Control

NASA Technical Reports Server (NTRS)

Jorgensen, Charles C.

1996-01-01

Neural networks are being developed at NASA Ames Research Center to permit real-time adaptive control of time varying nonlinear systems, enhance the fault-tolerance of mission hardware, and permit online system reconfiguration. In general, the problem of controlling time varying nonlinear systems with unknown structures has not been solved. Adaptive neural control techniques show considerable promise and are being applied to technical challenges including automated docking of spacecraft, dynamic balancing of the space station centrifuge, online reconfiguration of damaged aircraft, and reducing cost of new air and spacecraft designs. Our experiences have shown that neural network algorithms solved certain problems that conventional control methods have been unable to effectively address. These include damage mitigation in nonlinear reconfiguration flight control, early performance estimation of new aircraft designs, compensation for damaged planetary mission hardware by using redundant manipulator capability, and space sensor platform stabilization. This presentation explored these developments in the context of neural network control theory. The discussion began with an overview of why neural control has proven attractive for NASA application domains. The more important issues in control system development were then discussed with references to significant technical advances in the literature. Examples of how these methods have been applied were given, followed by projections of emerging application needs and directions.

Unmanned Aerial Vehicle Systems for Remote Estimation of Flooded Areas Based on Complex Image Processing.

PubMed

Popescu, Dan; Ichim, Loretta; Stoican, Florin

2017-02-23

Floods are natural disasters which cause the most economic damage at the global level. Therefore, flood monitoring and damage estimation are very important for the population, authorities and insurance companies. The paper proposes an original solution, based on a hybrid network and complex image processing, to this problem. As first novelty, a multilevel system, with two components, terrestrial and aerial, was proposed and designed by the authors as support for image acquisition from a delimited region. The terrestrial component contains a Ground Control Station, as a coordinator at distance, which communicates via the internet with more Ground Data Terminals, as a fixed nodes network for data acquisition and communication. The aerial component contains mobile nodes-fixed wing type UAVs. In order to evaluate flood damage, two tasks must be accomplished by the network: area coverage and image processing. The second novelty of the paper consists of texture analysis in a deep neural network, taking into account new criteria for feature selection and patch classification. Color and spatial information extracted from chromatic co-occurrence matrix and mass fractal dimension were used as well. Finally, the experimental results in a real mission demonstrate the validity of the proposed methodologies and the performances of the algorithms.

Unmanned Aerial Vehicle Systems for Remote Estimation of Flooded Areas Based on Complex Image Processing

PubMed Central

Popescu, Dan; Ichim, Loretta; Stoican, Florin

2017-01-01

Floods are natural disasters which cause the most economic damage at the global level. Therefore, flood monitoring and damage estimation are very important for the population, authorities and insurance companies. The paper proposes an original solution, based on a hybrid network and complex image processing, to this problem. As first novelty, a multilevel system, with two components, terrestrial and aerial, was proposed and designed by the authors as support for image acquisition from a delimited region. The terrestrial component contains a Ground Control Station, as a coordinator at distance, which communicates via the internet with more Ground Data Terminals, as a fixed nodes network for data acquisition and communication. The aerial component contains mobile nodes—fixed wing type UAVs. In order to evaluate flood damage, two tasks must be accomplished by the network: area coverage and image processing. The second novelty of the paper consists of texture analysis in a deep neural network, taking into account new criteria for feature selection and patch classification. Color and spatial information extracted from chromatic co-occurrence matrix and mass fractal dimension were used as well. Finally, the experimental results in a real mission demonstrate the validity of the proposed methodologies and the performances of the algorithms. PMID:28241479

Real-time earthquake monitoring: Early warning and rapid response

NASA Technical Reports Server (NTRS)

1991-01-01

A panel was established to investigate the subject of real-time earthquake monitoring (RTEM) and suggest recommendations on the feasibility of using a real-time earthquake warning system to mitigate earthquake damage in regions of the United States. The findings of the investigation and the related recommendations are described in this report. A brief review of existing real-time seismic systems is presented with particular emphasis given to the current California seismic networks. Specific applications of a real-time monitoring system are discussed along with issues related to system deployment and technical feasibility. In addition, several non-technical considerations are addressed including cost-benefit analysis, public perceptions, safety, and liability.

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

Pava, Daniel Seth

Los Alamos National Laboratory’s (LANL) trail management program goals include reduce risk of damage and injury to property, human life, and health, and sensitive natural and cultural resources from social trail use at LANL, facilitate the establishment of a safe viable network of linked trails, maintain security of LANL operations, and many more, respect the wishes of local Pueblos, adapt trail use to changing conditions in a responsive manner, and maintain the recreational functionality of the DOE lands. There are approximately 30 miles of LANL trails. Some are open to the public and allow bicycles, horses, hikers, and runners. Knowmore » the rules of the trails to stay safe.« less

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis

PubMed Central

Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-01-01

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia. PMID:25650663

Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis.

PubMed

Lin, Runhua; Xiao, Dejun; Guo, Yi; Tian, Dongping; Yun, Hailong; Chen, Donglin; Su, Min

2015-02-20

Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia.

New fronts emerge in the influenza cytokine storm.

PubMed

Guo, Xi-Zhi J; Thomas, Paul G

2017-07-01

Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a "cytokine storm," associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33-amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

Changes in translation rate modulate stress-induced damage of diverse proteins

PubMed Central

Kim, Heejung

2013-01-01

Proteostasis is the maintenance of the proper function of cellular proteins. Hypertonic stress disrupts proteostasis and causes rapid and widespread protein aggregation and misfolding in the nematode Caenorhabditis elegans. Optimal survival in hypertonic environments requires degradation of damaged proteins. Inhibition of protein synthesis occurs in response to diverse environmental stressors and may function in part to minimize stress-induced protein damage. We recently tested this idea directly and demonstrated that translation inhibition by acute exposure to cycloheximide suppresses hypertonicity-induced aggregation of polyglutamine::YFP (Q35::YFP) in body wall muscle cells. In this article, we further characterized the relationship between protein synthesis and hypertonic stress-induced protein damage. We demonstrate that inhibition of translation reduces hypertonic stress-induced formation and growth of Q35::YFP, Q44::YFP, and α-synuclein aggregates; misfolding of paramyosin and ras GTPase; and aggregation of multiple endogenous proteins expressed in diverse cell types. Activation of general control nonderepressible-2 (GCN-2) kinase signaling during hypertonic stress inhibits protein synthesis via phosphorylation of eukaryotic initiation factor-2α (eIF-2α). Inhibition of GCN-2 activation prevents the reduction in translation rate and greatly exacerbates the formation and growth of Q35::YFP aggregates and the aggregation of endogenous proteins. The current studies together with our previous work provide the first direct demonstration that hypertonic stress-induced reduction in protein synthesis minimizes protein aggregation and misfolding. Reduction in translation rate also serves as a signal that activates osmoprotective gene expression. The cellular proteostasis network thus plays a critical role in minimizing hypertonic stress-induced protein damage, in degrading stress-damaged proteins, and in cellular osmosensing and signaling. PMID:24153430

The impact of internet-connected control systems on the oil and gas industry

NASA Astrophysics Data System (ADS)

Martel, Ruth T.

In industry and infrastructure today, communication is a way of life. In the oil and gas industry, the use of devices that communicate with the network at large is both commonplace and expected. Unfortunately, security on these devices is not always best. Many industrial control devices originate from legacy devices not originally configured with security in mind. All infrastructure and industry today has seen an increase in attacks on their networks and in some cases, a very dramatic increase, which should be a cause for alarm and action. The purpose of this research was to highlight the threat that Internet-connected devices present to an organization's network in the oil and gas industry and ultimately, to the business and possibly even human life. Although there are several previous studies that highlight the problem of these Internet-connected devices, there remains evidence that security response has not been adequate. The analysis conducted on only one easily discovered device serves as an example of the ongoing issue of the security mindset in the oil and gas industry. The ability to connect to a network through an Internet-connected device gives a hacker an anonymous backdoor to do great damage in that network. The hope is that the approach to security in infrastructure and especially the oil and gas industry, changes before a major catastrophe occurs involving human life.

Trauma hemostasis and oxygenation research position paper on remote damage control resuscitation: definitions, current practice, and knowledge gaps.

PubMed

Jenkins, Donald H; Rappold, Joseph F; Badloe, John F; Berséus, Olle; Blackbourne, Lorne; Brohi, Karim H; Butler, Frank K; Cap, Andrew P; Cohen, Mitchell Jay; Davenport, Ross; DePasquale, Marc; Doughty, Heidi; Glassberg, Elon; Hervig, Tor; Hooper, Timothy J; Kozar, Rosemary; Maegele, Marc; Moore, Ernest E; Murdock, Alan; Ness, Paul M; Pati, Shibani; Rasmussen, Todd; Sailliol, Anne; Schreiber, Martin A; Sunde, Geir Arne; van de Watering, Leo M G; Ward, Kevin R; Weiskopf, Richard B; White, Nathan J; Strandenes, Geir; Spinella, Philip C

2014-05-01

The Trauma Hemostasis and Oxygenation Research Network held its third annual Remote Damage Control Resuscitation Symposium in June 2013 in Bergen, Norway. The Trauma Hemostasis and Oxygenation Research Network is a multidisciplinary group of investigators with a common interest in improving outcomes and safety in patients with severe traumatic injury. The network's mission is to reduce the risk of morbidity and mortality from traumatic hemorrhagic shock, in the prehospital phase of resuscitation through research, education, and training. The concept of remote damage control resuscitation is in its infancy, and there is a significant amount of work that needs to be done to improve outcomes for patients with life-threatening bleeding secondary to injury. The prehospital phase of resuscitation is critical in these patients. If shock and coagulopathy can be rapidly identified and minimized before hospital admission, this will very likely reduce morbidity and mortality. This position statement begins to standardize the terms used, provides an acceptable range of therapeutic options, and identifies the major knowledge gaps in the field.

Evolution of robustness to damage in artificial 3-dimensional development.

PubMed

Joachimczak, Michał; Wróbel, Borys

2012-09-01

GReaNs is an Artificial Life platform we have built to investigate the general principles that guide evolution of multicellular development and evolution of artificial gene regulatory networks. The embryos develop in GReaNs in a continuous 3-dimensional (3D) space with simple physics. The developmental trajectories are indirectly encoded in linear genomes. The genomes are not limited in size and determine the topology of gene regulatory networks that are not limited in the number of nodes. The expression of the genes is continuous and can be modified by adding environmental noise. In this paper we evolved development of structures with a specific shape (an ellipsoid) and asymmetrical pattering (a 3D pattern inspired by the French flag problem), and investigated emergence of the robustness to damage in development and the emergence of the robustness to noise. Our results indicate that both types of robustness are related, and that including noise during evolution promotes higher robustness to damage. Interestingly, we have observed that some evolved gene regulatory networks rely on noise for proper behaviour. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Tissue Damage Signaling Is a Prerequisite for Protective Neutrophil Recruitment to Microbial Infection in Zebrafish.

PubMed

Huang, Cong; Niethammer, Philipp

2018-05-15

Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate. By intravital imaging of zebrafish larvae, a powerful model for innate immunity, we show that prevention of tissue damage signaling upon microbial ear infection abrogates leukocyte chemotaxis and reduces animal survival, at least in part, through suppression of cytosolic phospholipase A 2 (cPla 2 ), which integrates tissue damage- and microbe-derived cues. Thus, microbial cues are insufficient, and damage signaling is essential for antimicrobial neutrophil responses in zebrafish. Copyright © 2018 Elsevier Inc. All rights reserved.

Rapid Modeling of and Response to Large Earthquakes Using Real-Time GPS Networks (Invited)

NASA Astrophysics Data System (ADS)

Crowell, B. W.; Bock, Y.; Squibb, M. B.

2010-12-01

Real-time GPS networks have the advantage of capturing motions throughout the entire earthquake cycle (interseismic, seismic, coseismic, postseismic), and because of this, are ideal for real-time monitoring of fault slip in the region. Real-time GPS networks provide the perfect supplement to seismic networks, which operate with lower noise and higher sampling rates than GPS networks, but only measure accelerations or velocities, putting them at a supreme disadvantage for ascertaining the full extent of slip during a large earthquake in real-time. Here we report on two examples of rapid modeling of recent large earthquakes near large regional real-time GPS networks. The first utilizes Japan’s GEONET consisting of about 1200 stations during the 2003 Mw 8.3 Tokachi-Oki earthquake about 100 km offshore Hokkaido Island and the second investigates the 2010 Mw 7.2 El Mayor-Cucapah earthquake recorded by more than 100 stations in the California Real Time Network. The principal components of strain were computed throughout the networks and utilized as a trigger to initiate earthquake modeling. Total displacement waveforms were then computed in a simulated real-time fashion using a real-time network adjustment algorithm that fixes a station far away from the rupture to obtain a stable reference frame. Initial peak ground displacement measurements can then be used to obtain an initial size through scaling relationships. Finally, a full coseismic model of the event can be run minutes after the event, given predefined fault geometries, allowing emergency first responders and researchers to pinpoint the regions of highest damage. Furthermore, we are also investigating using total displacement waveforms for real-time moment tensor inversions to look at spatiotemporal variations in slip.

Unique aspects of the perinatal immune system.

PubMed

Zhang, Xiaoming; Zhivaki, Dania; Lo-Man, Richard

2017-08-01

The early stages of life are associated with increased susceptibility to infection, which is in part due to an ineffective immune system. In the context of infection, the immune system must be stimulated to provide efficient protection while avoiding insufficient or excessive activation. Yet, in early life, age-dependent immune regulation at molecular and cellular levels contributes to a reduced immunological fitness in terms of pathogen clearance and response to vaccines. To enable microbial colonization to be tolerated at birth, epigenetic immune cell programming and early life-specific immune regulatory and effector mechanisms ensure that vital functions and organ development are supported and that tissue damage is avoided. Advancement in our understanding of age-related remodelling of immune networks and the consequent tuning of immune responsiveness will open up new possibilities for immune intervention and vaccine strategies that are designed specifically for early life.

Development of a remote sensing network for time-sensitive detection of fine scale damage to transportation infrastructure : [final report].

DOT National Transportation Integrated Search

2015-09-23

This research project aimed to develop a remote sensing system capable of rapidly identifying fine-scale damage to critical transportation infrastructure following hazard events. Such a system must be pre-planned for rapid deployment, automate proces...

On impact damage detection and quantification for CFRP laminates using structural response data only

NASA Astrophysics Data System (ADS)

Sultan, M. T. H.; Worden, K.; Pierce, S. G.; Hickey, D.; Staszewski, W. J.; Dulieu-Barton, J. M.; Hodzic, A.

2011-11-01

The overall purpose of the research is to detect and attempt to quantify impact damage in structures made from composite materials. A study that uses simplified coupon specimens made from a Carbon Fibre-Reinforced Polymer (CFRP) prepreg with 11, 12 and 13 plies is presented. PZT sensors were placed at three separate locations in each test specimen to record the responses from impact events. To perform damaging impact tests, an instrumented drop-test machine was used and the impact energy was set to cover a range of 0.37-41.72 J. The response signals captured from each sensor were recorded by a data acquisition system for subsequent evaluation. The impacted specimens were examined with an X-ray technique to determine the extent of the damaged areas and it was found that the apparent damaged area grew monotonically with impact energy. A number of simple univariate and multivariate features were extracted from the sensor signals recorded during impact by computing their spectra and calculating frequency centroids. The concept of discordancy from the statistical discipline of outlier analysis is employed in order to separate the responses from non-damaging and damaging impacts. The results show that the potential damage indices introduced here provide a means of identifying damaging impacts from the response data alone.

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Scaling the Non-linear Impact Response of Flat and Curved Composite Panels

NASA Technical Reports Server (NTRS)

Ambur, Damodar R.; Chunchu, Prasad B.; Rose, Cheryl A.; Feraboli, Paolo; Jackson, Wade C.

2005-01-01

The application of scaling laws to thin flat and curved composite panels exhibiting nonlinear response when subjected to low-velocity transverse impact is investigated. Previous research has shown that the elastic impact response of structural configurations exhibiting geometrically linear response can be effectively scaled. In the present paper, a preliminary experimental study is presented to assess the applicability of the scaling laws to structural configurations exhibiting geometrically nonlinear deformations. The effect of damage on the scalability of the structural response characteristics, and the effect of scale on damage development are also investigated. Damage is evaluated using conventional methods including C-scan, specimen de-plying and visual inspection of the impacted panels. Coefficient of restitution and normalized contact duration are also used to assess the extent of damage. The results confirm the validity of the scaling parameters for elastic impacts. However, for the panels considered in the study, the extent and manifestation of damage do not scale according to the scaling laws. Furthermore, the results indicate that even though the damage does not scale, the overall panel response characteristics, as indicated by contact force profiles, do scale for some levels of damage.

Response to DNA damage of CHEK2 missense mutations in familial breast cancer

PubMed Central

Roeb, Wendy; Higgins, Jake; King, Mary-Claire

2012-01-01

Comprehensive sequencing of tumor suppressor genes to evaluate inherited predisposition to cancer yields many individually rare missense alleles of unknown functional and clinical consequence. To address this problem for CHEK2 missense alleles, we developed a yeast-based assay to assess in vivo CHEK2-mediated response to DNA damage. Of 25 germline CHEK2 missense alleles detected in familial breast cancer patients, 12 alleles had complete loss of DNA damage response, 8 had partial loss and 5 exhibited a DNA damage response equivalent to that mediated by wild-type CHEK2. Variants exhibiting reduced response to DNA damage were found in all domains of the CHEK2 protein. Assay results were in agreement with epidemiologic assessments of breast cancer risk for those variants sufficiently common for case–control studies to have been undertaken. Assay results were largely concordant with consensus predictions of in silico tools, particularly for damaging alleles in the kinase domain. However, of the 25 variants, 6 were not consistently classifiable by in silico tools. An in vivo assay of cellular response to DNA damage by mutant CHEK2 alleles may complement and extend epidemiologic and genetic assessment of their clinical consequences. PMID:22419737

Response to DNA damage of CHEK2 missense mutations in familial breast cancer.

PubMed

Roeb, Wendy; Higgins, Jake; King, Mary-Claire

2012-06-15

Comprehensive sequencing of tumor suppressor genes to evaluate inherited predisposition to cancer yields many individually rare missense alleles of unknown functional and clinical consequence. To address this problem for CHEK2 missense alleles, we developed a yeast-based assay to assess in vivo CHEK2-mediated response to DNA damage. Of 25 germline CHEK2 missense alleles detected in familial breast cancer patients, 12 alleles had complete loss of DNA damage response, 8 had partial loss and 5 exhibited a DNA damage response equivalent to that mediated by wild-type CHEK2. Variants exhibiting reduced response to DNA damage were found in all domains of the CHEK2 protein. Assay results were in agreement with epidemiologic assessments of breast cancer risk for those variants sufficiently common for case-control studies to have been undertaken. Assay results were largely concordant with consensus predictions of in silico tools, particularly for damaging alleles in the kinase domain. However, of the 25 variants, 6 were not consistently classifiable by in silico tools. An in vivo assay of cellular response to DNA damage by mutant CHEK2 alleles may complement and extend epidemiologic and genetic assessment of their clinical consequences.

Feasibility study of earthquake early warning (EEW) in Hawaii

USGS Publications Warehouse

Thelen, Weston A.; Hotovec-Ellis, Alicia J.; Bodin, Paul

2016-09-30

The effects of earthquake shaking on the population and infrastructure across the State of Hawaii could be catastrophic, and the high seismic hazard in the region emphasizes the likelihood of such an event. Earthquake early warning (EEW) has the potential to give several seconds of warning before strong shaking starts, and thus reduce loss of life and damage to property. The two approaches to EEW are (1) a network approach (such as ShakeAlert or ElarmS) where the regional seismic network is used to detect the earthquake and distribute the alarm and (2) a local approach where a critical facility has a single seismometer (or small array) and a warning system on the premises.The network approach, also referred to here as ShakeAlert or ElarmS, uses the closest stations within a regional seismic network to detect and characterize an earthquake. Most parameters used for a network approach require observations on multiple stations (typically 3 or 4), which slows down the alarm time slightly, but the alarms are generally more reliable than with single-station EEW approaches. The network approach also benefits from having stations closer to the source of any potentially damaging earthquake, so that alarms can be sent ahead to anyone who subscribes to receive the notification. Thus, a fully implemented ShakeAlert system can provide seconds of warning for both critical facilities and general populations ahead of damaging earthquake shaking.The cost to implement and maintain a fully operational ShakeAlert system is high compared to a local approach or single-station solution, but the benefits of a ShakeAlert system would be felt statewide—the warning times for strong shaking are potentially longer for most sources at most locations.The local approach, referred to herein as “single station,” uses measurements from a single seismometer to assess whether strong earthquake shaking can be expected. Because of the reliance on a single station, false alarms are more common than when using a regional network of seismometers. Given the current network, a single-station approach provides more warning for damaging earthquakes that occur close to the station, but it would have limited benefit compared to a fully implemented ShakeAlert system. For Honolulu, for example, the single-station approach provides an advantage over ShakeAlert only for earthquakes that occur in a narrow zone extending northeast and southwest of O‘ahu. Instrumentation and alarms associated with the single-station approach are typically maintained and assessed within the target facility, and thus no outside connectivity is required. A single-station approach, then, is unlikely to help broader populations beyond the individuals at the target facility, but they have the benefit of being commercially available for relatively little cost. The USGS Hawaiian Volcano Observatory (HVO) is the Advanced National Seismic System (ANSS) regional seismic network responsible for locating and characterizing earthquakes across the State of Hawaii. During 2014 and 2015, HVO tested a network-based EEW algorithm within the current seismic network in order to assess the suitability for building a full EEW system. Using the current seismic instrumentation and processing setup at HVO, it is possible for a network approach to release an alarm a little more than 3 seconds after the earthquake is recorded on the fourth seismometer. Presently, earthquakes having M≥3 detected with the ElarmS algorithm have an average location error of approximately 4.5 km and an average magnitude error of -0.3 compared to the reviewed catalog locations from the HVO. Additional stations and upgrades to existing seismic stations would serve to improve solution precision and warning times and additional staffing would be required to provide support for a robust, network-based EEW system. For a critical facility on the Island of Hawaiʻi, such as the telescopes atop Mauna Kea, one phased approach to mitigate losses could be to immediately install a single station system to establish some level of warning. Subsequently, supporting the implementation of a full network-based EEW system on the Island of Hawaiʻi would provide additional benefit in the form of improved warning times once the system is fully installed and operational, which may take several years. Distributed populations across the Hawaiian Islands, including those outside the major cities and far from the likely earthquake source areas, would likely only benefit from a network approach such as ShakeAlert to provide warnings of strong shaking.

A vibro-haptic human-machine interface for structural health monitoring

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

Mascarenas, David; Plont, Crystal; Brown, Christina

The structural health monitoring (SHM) community’s goal has been to endow physical systems with a nervous system not unlike those commonly found in living organisms. Typically the SHM community has attempted to do this by instrumenting structures with a variety of sensors, and then applying various signal processing and classification procedures to the data in order to detect the presence of damage, the location of damage, the severity of damage, and to estimate the remaining useful life of the structure. This procedure has had some success, but we are still a long way from achieving the performance of nervous systemsmore » found in biology. This is primarily because contemporary classification algorithms do not have the performance required. In many cases expert judgment is superior to automated classification. This work introduces a new paradigm. We propose interfacing the human nervous system to the distributed sensor network located on the structure and developing new techniques to enable human-machine cooperation. Results from the field of sensory substitution suggest this should be possible. This study investigates a vibro-haptic human-machine interface for SHM. The investigation was performed using a surrogate three-story structure. The structure features three nonlinearity-inducing bumpers to simulate damage. Accelerometers are placed on each floor to measure the response of the structure to a harmonic base excitation. The accelerometer measurements are preprocessed. As a result, the preprocessed data is then encoded encoded as a vibro-tactile stimulus. Human subjects were then subjected to the vibro-tactile stimulus and asked to characterize the damage in the structure.« less

A vibro-haptic human-machine interface for structural health monitoring

DOE PAGES

Mascarenas, David; Plont, Crystal; Brown, Christina; ...

2014-11-01

The structural health monitoring (SHM) community’s goal has been to endow physical systems with a nervous system not unlike those commonly found in living organisms. Typically the SHM community has attempted to do this by instrumenting structures with a variety of sensors, and then applying various signal processing and classification procedures to the data in order to detect the presence of damage, the location of damage, the severity of damage, and to estimate the remaining useful life of the structure. This procedure has had some success, but we are still a long way from achieving the performance of nervous systemsmore » found in biology. This is primarily because contemporary classification algorithms do not have the performance required. In many cases expert judgment is superior to automated classification. This work introduces a new paradigm. We propose interfacing the human nervous system to the distributed sensor network located on the structure and developing new techniques to enable human-machine cooperation. Results from the field of sensory substitution suggest this should be possible. This study investigates a vibro-haptic human-machine interface for SHM. The investigation was performed using a surrogate three-story structure. The structure features three nonlinearity-inducing bumpers to simulate damage. Accelerometers are placed on each floor to measure the response of the structure to a harmonic base excitation. The accelerometer measurements are preprocessed. As a result, the preprocessed data is then encoded encoded as a vibro-tactile stimulus. Human subjects were then subjected to the vibro-tactile stimulus and asked to characterize the damage in the structure.« less

Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1

PubMed Central

Balmus, Gabriel; Zhu, Min; Mukherjee, Sucheta; Lyndaker, Amy M.; Hume, Kelly R.; Lee, Jaesung; Riccio, Mark L.; Reeves, Anthony P.; Sutter, Nathan B.; Noden, Drew M.; Peters, Rachel M.; Weiss, Robert S.

2012-01-01

The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and increased cancer predisposition. ATM is central to a pathway that responds to double-strand DNA breaks, whereas the related kinase ATR leads a parallel signaling cascade that is activated by replication stress. To dissect the physiological relationship between the ATM and ATR pathways, we generated mice defective for both. Because complete ATR pathway inactivation causes embryonic lethality, we weakened the ATR mechanism to different degrees by impairing HUS1, a member of the 911 complex that is required for efficient ATR signaling. Notably, simultaneous ATM and HUS1 defects caused synthetic lethality. Atm/Hus1 double-mutant embryos showed widespread apoptosis and died mid-gestationally. Despite the underlying DNA damage checkpoint defects, increased DNA damage signaling was observed, as evidenced by H2AX phosphorylation and p53 accumulation. A less severe Hus1 defect together with Atm loss resulted in partial embryonic lethality, with the surviving double-mutant mice showing synergistic increases in genomic instability and specific developmental defects, including dwarfism, craniofacial abnormalities and brachymesophalangy, phenotypes that are observed in several human genomic instability disorders. In addition to identifying tissue-specific consequences of checkpoint dysfunction, these data highlight a robust, cooperative configuration for the mammalian DNA damage response network and further suggest HUS1 and related genes in the ATR pathway as candidate modifiers of disease severity in A-T patients. PMID:22575700

Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs

PubMed Central

Harris, Robin E; Setiawan, Linda; Saul, Josh; Hariharan, Iswar K

2016-01-01

Many organisms lose the capacity to regenerate damaged tissues as they mature. Damaged Drosophila imaginal discs regenerate efficiently early in the third larval instar (L3) but progressively lose this ability. This correlates with reduced damage-responsive expression of multiple genes, including the WNT genes wingless (wg) and Wnt6. We demonstrate that damage-responsive expression of both genes requires a bipartite enhancer whose activity declines during L3. Within this enhancer, a damage-responsive module stays active throughout L3, while an adjacent silencing element nucleates increasing levels of epigenetic silencing restricted to this enhancer. Cas9-mediated deletion of the silencing element alleviates WNT repression, but is, in itself, insufficient to promote regeneration. However, directing Myc expression to the blastema overcomes repression of multiple genes, including wg, and restores cellular responses necessary for regeneration. Localized epigenetic silencing of damage-responsive enhancers can therefore restrict regenerative capacity in maturing organisms without compromising gene functions regulated by developmental signals. DOI: http://dx.doi.org/10.7554/eLife.11588.001 PMID:26840050

Neural Models: An Option to Estimate Seismic Parameters of Accelerograms

NASA Astrophysics Data System (ADS)

Alcántara, L.; García, S.; Ovando-Shelley, E.; Macías, M. A.

2014-12-01

Seismic instrumentation for recording strong earthquakes, in Mexico, goes back to the 60´s due the activities carried out by the Institute of Engineering at Universidad Nacional Autónoma de México. However, it was after the big earthquake of September 19, 1985 (M=8.1) when the project of seismic instrumentation assumes a great importance. Currently, strong ground motion networks have been installed for monitoring seismic activity mainly along the Mexican subduction zone and in Mexico City. Nevertheless, there are other major regions and cities that can be affected by strong earthquakes and have not yet begun their seismic instrumentation program or this is still in development.Because of described situation some relevant earthquakes (e.g. Huajuapan de León Oct 24, 1980 M=7.1, Tehuacán Jun 15, 1999 M=7 and Puerto Escondido Sep 30, 1999 M= 7.5) have not been registered properly in some cities, like Puebla and Oaxaca, and that were damaged during those earthquakes. Fortunately, the good maintenance work carried out in the seismic network has permitted the recording of an important number of small events in those cities. So in this research we present a methodology based on the use of neural networks to estimate significant duration and in some cases the response spectra for those seismic events. The neural model developed predicts significant duration in terms of magnitude, epicenter distance, focal depth and soil characterization. Additionally, for response spectra we used a vector of spectral accelerations. For training the model we selected a set of accelerogram records obtained from the small events recorded in the strong motion instruments installed in the cities of Puebla and Oaxaca. The final results show that neural networks as a soft computing tool that use a multi-layer feed-forward architecture provide good estimations of the target parameters and they also have a good predictive capacity to estimate strong ground motion duration and response spectra.

Possible role of interference, protein noise, and sink effects in nonphotochemical quenching in photosynthetic complexes

DOE PAGES

Berman, Gennady P.; Nesterov, Alexander I.; Gurvitz, Shmuel; ...

2016-04-30

Here, we analyze theoretically a simple and consistent quantum mechanical model that reveals the possible role of quantum interference, protein noise, and sink effects in the nonphotochemical quenching (NPQ) in light-harvesting complexes (LHCs). The model consists of a network of five interconnected sites (excitonic states of light-sensitive molecules) responsible for the NPQ mechanism. The model also includes the “damaging” and the dissipative channels. The damaging channel is responsible for production of singlet oxygen and other destructive outcomes. In this model, both damaging and “dissipative” charge transfer channels are described by discrete electron energy levels attached to their sinks, that mimicmore » the continuum part of electron energy spectrum. All five excitonic sites interact with the protein environment that is modeled using a stochastic process. Our approach allowed us to derive the exact and closed system of linear ordinary differential equations for the reduced density matrix and its first momentums. Moreover, these equations are solved numerically including for strong interactions between the light-sensitive molecules and protein environment. As an example, we apply our model to demonstrate possible contributions of quantum interference, protein noise, and sink effects in the NPQ mechanism in the CP29 minor LHC. The numerical simulations show that using proper combination of quantum interference effects, properties of noise, and sinks, one can significantly suppress the damaging channel. Finally, our findings demonstrate the possible role of interference, protein noise, and sink effects for modeling, engineering, and optimizing the performance of the NPQ processes in both natural and artificial light-harvesting complexes.« less

Indirect diagnosis of pavement structural damages using surface GPR reflection techniques

NASA Astrophysics Data System (ADS)

Benedetto, A.; Pensa, S.

2007-06-01

The safety and operability of road networks is, in part, dependent on the quality of the pavement. It is known that pavements suffer from many different structural problems which can lead to damage to the pavement surface. To minimize the effect of these problems programmed policies for pavement management are required. Additionally a given local anomaly on the road surface can affect the safety of the road to various degrees according to the category of the road, so it is possible to set up different programmes of repair according to the different standards of road. Programmed policies for pavement management are required because of the wide structural damage which occurs to pavements during their normal operating life. This has consequences for the safety and operability of road networks. During the last decade, road networks suffered from great structural damage. The damage occurs for different reasons, such as the increasing traffic or the lack of means for routine maintenance. Many forms of damage, originating in the bottom layers are invisible until the pavement cracks. They depend on the infiltration of water and the presence of cohesive soil greatly reduces the bearing capacity of the sub-asphalt layers and underlying soils. On the basis of an in-depth literature review, an experimental survey with Ground Penetrating Radar (GPR) was carried out to calibrate the geophysical parameters and to validate the reliability of an indirect diagnostic method of pavement damage. The experiments were set on a pavement under which water was injected over a period of several hours. GPR travel time data were used to estimate the dielectric constant and the water content in the unbound aggregate layer, the variations in water content with time and particular areas where rate of infiltration decreases. A new methodology has been proposed to extract the hydraulic permittivity fields in sub-asphalt structural layers and soils from the moisture maps observed with GPR. It is effective at diagnosing the presence of clay or cohesive soil that compromises the bearing capacity of sub-base and induces damage.

Application of a neural network as a potential aid in predicting NTF pump failure

NASA Technical Reports Server (NTRS)

Rogers, James L.; Hill, Jeffrey S.; Lamarsh, William J., II; Bradley, David E.

1993-01-01

The National Transonic Facility has three centrifugal multi-stage pumps to supply liquid nitrogen to the wind tunnel. Pump reliability is critical to facility operation and test capability. A highly desirable goal is to be able to detect a pump rotating component problem as early as possible during normal operation and avoid serious damage to other pump components. If a problem is detected before serious damage occurs, the repair cost and downtime could be reduced significantly. A neural network-based tool was developed for monitoring pump performance and aiding in predicting pump failure. Once trained, neural networks can rapidly process many combinations of input values other than those used for training to approximate previously unknown output values. This neural network was applied to establish relationships among the critical frequencies and aid in predicting failures. Training pairs were developed from frequency scans from typical tunnel operations. After training, various combinations of critical pump frequencies were propagated through the neural network. The approximated output was used to create a contour plot depicting the relationships of the input frequencies to the output pump frequency.

Electro-purification of carbon nanotube networks without damaging the assembly structure and crystallinity

NASA Astrophysics Data System (ADS)

Yang, Xueqin; Yang, Ming; Zhang, Huichao; Zhao, Jingna; Zhang, Xiaohua; Li, Qingwen

2018-06-01

Fe-containing nanoparticles are of a high mass fraction in the as-grown carbon nanotube (CNT) network. By controlling the S-to-Fe atom ratio in the growth feedstock and introducing water as a weak oxidant, highly crystalline few-walled CNT network can be obtained, with a mass fraction of over 20 wt% for the Fe-containing nanoparticles. We report here an electron-oxidation-based purification method to efficiently remove the Fe-containing nanoparticles without inducing clear damage to either the assembly structure or the tube crystallinity. The purification could increase the ratio between Raman D and G peak intensities slightly from 0.08 to 0.12, decrease the specific conductivity from 0.31 to 0.24 S m2/g and the Fe content from >20 wt% to ≈1 wt%, and modify the capacitance just by about 13 F/g. All these indicate that the CNT network was well maintained by such gentle electro-oxidation-based purification. In addition, the purified CNT network can exhibit advantages in mechanical and electrical applications.

Hepatoprotective activity of sea cucumber Phyllophorus sp. extract in carp (Cyprinus carpio)

NASA Astrophysics Data System (ADS)

Sulmartiwi, Laksmi; Triastuti, Juni; Andriyono, Sapto; Umami, Mardiah Rahma

2017-02-01

Many procedures continuously in aquaculture and scientific research like tagging and vaccinating cause pain, involving damaging tissue and also cause stress responses in fish. Stress responses in fish influence liver because liver have vital role to supply energy and metabolism. Histology alteration in liver is caused by stress response like changes of vacuolation hepatocyte and characteristic colour. Triterpenoid was known had hepatoprotective activity. One of marine organism contained triterpenoid was sea cucumber. Result of research showed that liver tissue in fish with injected acetic acid 5 % (in upper lip) as pain stimulus have histopathology damages such as pyknosis (medium damage level) and oedema (heavy damage level) after 8 hour injection. Injected Lidocaine 1mg/fish as analgesic drug have histopathology damages such as oedema (heavy damages level), necrosis and pyknosis (low damages level). Injected acetic acid 5 % (in upper lip) and ethanolic extract of sea cucumber Phyllophorus sp. dose 5 mg/50 gr body weight shown histopathology damages such as necrosis, edema (medium damage level) and pyknosis (low damage level).

Integrated Physiological, Proteomic, and Metabolomic Analysis of Ultra Violet (UV) Stress Responses and Adaptation Mechanisms in Pinus radiata*

PubMed Central

Pascual, Jesús; Cañal, María Jesús; Escandón, Mónica; Meijón, Mónica; Weckwerth, Wolfram

2017-01-01

Globally expected changes in environmental conditions, especially the increase of UV irradiation, necessitate extending our knowledge of the mechanisms mediating tree species adaptation to this stress. This is crucial for designing new strategies to maintain future forest productivity. Studies focused on environmentally realistic dosages of UV irradiation in forest species are scarce. Pinus spp. are commercially relevant trees and not much is known about their adaptation to UV. In this work, UV treatment and recovery of Pinus radiata plants with dosages mimicking future scenarios, based on current models of UV radiation, were performed in a time-dependent manner. The combined metabolome and proteome analysis were complemented with measurements of + physiological parameters and gene expression. Sparse PLS analysis revealed complex molecular interaction networks of molecular and physiological data. Early responses prevented phototoxicity by reducing photosystem activity and the electron transfer chain together with the accumulation of photoprotectors and photorespiration. Apart from the reduction in photosynthesis as consequence of the direct UV damage on the photosystems, the primary metabolism was rearranged to deal with the oxidative stress while minimizing ROS production. New protein kinases and proteases related to signaling, coordination, and regulation of UV stress responses were revealed. All these processes demonstrate a complex molecular interaction network extending the current knowledge on UV-stress adaptation in pine. PMID:28096192

Modal Frequency Detection in Composite Beams Using Fiber Optic Sensors

DTIC Science & Technology

1997-04-18

Structures 4, 270-280 (1995). [35] Chen-Jung Li and Ray Asok , "Neural Network Representation of Fatigue Damage Dynamics," Smart Materials and Structures 3...37] Roland Ray Kilcher, "Modal Analysis and Impact Damage Assessment of Composite Laminates: an Experimental Study," M.S. thesis, University of

Suggested Mechanisms of Tracheal Occlusion Mediated Accelerated Fetal Lung Growth: A Case for Heterogeneous Topological Zones

PubMed Central

Marwan, Ahmed I.; Shabeka, Uladzimir; Dobrinskikh, Evgenia

2018-01-01

In this article, we report an up-to-date summary on tracheal occlusion (TO) as an approach to drive accelerated lung growth and strive to review the different maternal- and fetal-derived local and systemic signals and mechanisms that may play a significant biological role in lung growth and formation of heterogeneous topological zones following TO. Pulmonary hypoplasia is a condition whereby branching morphogenesis and embryonic pulmonary vascular development are globally affected and is classically seen in congenital diaphragmatic hernia. TO is an innovative approach aimed at driving accelerated lung growth in the most severe forms of diaphragmatic hernia and has been shown to result in improved neonatal outcomes. Currently, most research on mechanisms of TO-induced lung growth is focused on mechanical forces and is viewed from the perspective of homogeneous changes within the lung. We suggest that the key principle in understanding changes in fetal lungs after TO is taking into account formation of unique variable topological zones. Following TO, fetal lungs might temporarily look like a dynamically changing topologic mosaic with varying proliferation rates, dissimilar scale of vasculogenesis, diverse patterns of lung tissue damage, variable metabolic landscape, and different structures. The reasons for this dynamic topological mosaic pattern may include distinct degree of increased hydrostatic pressure in different parts of the lung, dissimilar degree of tissue stress/damage and responses to this damage, and incomparable patterns of altered lung zones with variable response to systemic maternal and fetal factors, among others. The local interaction between these factors and their accompanying processes in addition to the potential role of other systemic factors might lead to formation of a common vector of biological response unique to each zone. The study of the interaction between various networks formed after TO (action of mechanical forces, activation of mucosal mast cells, production and secretion of damage-associated molecular pattern substances, low-grade local pulmonary inflammation, and cardiac contraction-induced periodic agitation of lung tissue, among others) will bring us closer to an appreciation of the biological phenomenon of topological heterogeneity within the fetal lungs. PMID:29376042

Construction of local gene network for revealing different liver function of rats fed deep-fried oil with or without resistant starch.

PubMed

Wang, Zhiwei; Liao, Tianqi; Zhou, Zhongkai; Wang, Yuyang; Diao, Yongjia; Strappe, Padraig; Prenzler, Paul; Ayton, Jamie; Blanchard, Chris

2016-09-06

To study the mechanism underlying the liver damage induced by deep-fried oil (DO) consumption and the beneficial effects from resistant starch (RS) supplement, differential gene expression and pathway network were analyzed based on RNA sequencing data from rats. The up/down regulated genes and corresponding signaling pathways were used to construct a novel local gene network (LGN). The topology of the network showed characteristics of small-world network, with some pathways demonstrating a high degree. Some changes in genes led to a larger probability occurrence of disease or infection with DO intake. More importantly, the main pathways were found to be almost the same between the two LGNs (30 pathways overlapped in total 48) with gene expression profile. This finding may indicate that RS supplement in DO-containing diet may mainly regulate the genes that related to DO damage, and RS in the diet may provide direct signals to the liver cells and modulate its effect through a network involving complex gene regulatory events. It is the first attempt to reveal the mechanism of the attenuation of liver dysfunction from RS supplement in the DO-containing diet using differential gene expression and pathway network. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Flood impacts on a water distribution network

NASA Astrophysics Data System (ADS)

Arrighi, Chiara; Tarani, Fabio; Vicario, Enrico; Castelli, Fabio

2017-12-01

Floods cause damage to people, buildings and infrastructures. Water distribution systems are particularly exposed, since water treatment plants are often located next to the rivers. Failure of the system leads to both direct losses, for instance damage to equipment and pipework contamination, and indirect impact, since it may lead to service disruption and thus affect populations far from the event through the functional dependencies of the network. In this work, we present an analysis of direct and indirect damages on a drinking water supply system, considering the hazard of riverine flooding as well as the exposure and vulnerability of active system components. The method is based on interweaving, through a semi-automated GIS procedure, a flood model and an EPANET-based pipe network model with a pressure-driven demand approach, which is needed when modelling water distribution networks in highly off-design conditions. Impact measures are defined and estimated so as to quantify service outage and potential pipe contamination. The method is applied to the water supply system of the city of Florence, Italy, serving approximately 380 000 inhabitants. The evaluation of flood impact on the water distribution network is carried out for different events with assigned recurrence intervals. Vulnerable elements exposed to the flood are identified and analysed in order to estimate their residual functionality and to simulate failure scenarios. Results show that in the worst failure scenario (no residual functionality of the lifting station and a 500-year flood), 420 km of pipework would require disinfection with an estimated cost of EUR 21 million, which is about 0.5 % of the direct flood losses evaluated for buildings and contents. Moreover, if flood impacts on the water distribution network are considered, the population affected by the flood is up to 3 times the population directly flooded.

Features of Microglia and Neuroinflammation Relevant to Environmental Exposure and Neurotoxicity

PubMed Central

Kraft, Andrew D.; Harry, G. Jean

2011-01-01

Microglia are resident cells of the brain involved in regulatory processes critical for development, maintenance of the neural environment, injury and repair. They belong to the monocytic-macrophage lineage and serve as brain immune cells to orchestrate innate immune responses; however, they are distinct from other tissue macrophages due to their relatively quiescent phenotype and tight regulation by the CNS microenvironment. Microglia actively survey the surrounding parenchyma and respond rapidly to changes such that any disruption to neural architecture or function can contribute to the loss in regulation of the microglia phenotype. In many models of neurodegeneration and neurotoxicity, early events of synaptic degeneration and neuronal loss are accompanied by an inflammatory response including activation of microglia, perivascular monocytes, and recruitment of leukocytes. In culture, microglia have been shown to be capable of releasing several potentially cytotoxic substances, such as reactive oxygen intermediates, nitric oxide, proteases, arachidonic acid derivatives, excitatory amino acids, and cytokines; however, they also produce various neurotrophic factors and quench damage from free radicals and excitotoxins. As the primary source for pro-inflammatory cytokines, microglia are implicated as pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Neuroinflammation should be considered as a balanced network of processes whereby subtle modifications can shift the cells toward disparate outcomes. For any evaluation of neuroinflammation and microglial responses, within the framework of neurotoxicity or degeneration, one key question in determining the consequence of neuroinflammation is whether the response is an initiating event or the consequence of tissue damage. As examples of environmental exposure-related neuroinflammation in the literature, we provide an evaluation of data on manganese and diesel exhaust particles. PMID:21845170

Destabilization of the MutSα's protein-protein interface due to binding to the DNA adduct induced by anticancer agent carboplatin via molecular dynamics simulations.

PubMed

Negureanu, Lacramioara; Salsbury, Freddie R

2013-11-01

DNA mismatch repair (MMR) proteins maintain genetic integrity in all organisms by recognizing and repairing DNA errors. Such alteration of hereditary information can lead to various diseases, including cancer. Besides their role in DNA repair, MMR proteins detect and initiate cellular responses to certain type of DNA damage. Its response to the damaged DNA has made the human MMR pathway a useful target for anticancer agents such as carboplatin. This study indicates that strong, specific interactions at the interface of MutSα in response to the mismatched DNA recognition are replaced by weak, non-specific interactions in response to the damaged DNA recognition. Data suggest a severe impairment of the dimerization of MutSα in response to the damaged DNA recognition. While the core of MutSα is preserved in response to the damaged DNA recognition, the loss of contact surface and the rearrangement of contacts at the protein interface suggest a different packing in response to the damaged DNA recognition. Coupled in response to the mismatched DNA recognition, interaction energies, hydrogen bonds, salt bridges, and solvent accessible surface areas at the interface of MutSα and within the subunits are uncoupled or asynchronously coupled in response to the damaged DNA recognition. These pieces of evidence suggest that the loss of a synchronous mode of response in the MutSα's surveillance for DNA errors would possibly be one of the mechanism(s) of signaling the MMR-dependent programed cell death much wanted in anticancer therapies. The analysis was drawn from dynamics simulations.

Using chaotic forcing to detect damage in a structure

USGS Publications Warehouse

Moniz, L.; Nichols, J.; Trickey, S.; Seaver, M.; Pecora, D.; Pecora, L.

2005-01-01

In this work we develop a numerical test for Holder continuity and apply it and another test for continuity to the difficult problem of detecting damage in structures. We subject a thin metal plate with incremental damage to the plate changes, its filtering properties, and therefore the phase space trajectories of the response chaotic excitation of various bandwidths. Damage to the plate changes its filtering properties and therefore the phase space of the response. Because the data are multivariate (the plate is instrumented with multiple sensors) we use a singular value decomposition of the set of the output time series to reduce the embedding dimension of the response time series. We use two geometric tests to compare an attractor reconstructed from data from an undamaged structure to that reconstructed from data from a damaged structure. These two tests translate to testing for both generalized and differentiable synchronization between responses. We show loss of synchronization of responses with damage to the structure. ?? 2005 American Institute of Physics.

Using chaotic forcing to detect damage in a structure.

USGS Publications Warehouse

Moniz, L.; Nichols, J.; Trickey, S.; Seaver, M.; Pecora, D.; Pecora, L.

2005-01-01

In this work we develop a numerical test for Holder continuity and apply it and another test for continuity to the difficult problem of detecting damage in structures. We subject a thin metal plate with incremental damage to the plate changes, its filtering properties, and therefore the phase space trajectories of the response chaotic excitation of various bandwidths. Damage to the plate changes its filtering properties and therefore the phase space of the response. Because the data are multivariate (the plate is instrumented with multiple sensors) we use a singular value decomposition of the set of the output time series to reduce the embedding dimension of the response time series. We use two geometric tests to compare an attractor reconstructed from data from an undamaged structure to that reconstructed from data from a damaged structure. These two tests translate to testing for both generalized and differentiable synchronization between responses. We show loss of synchronization of responses with damage to the structure.

DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks

PubMed Central

Kreuzer, Kenneth N.

2013-01-01

Recent advances in the area of bacterial DNA damage responses are reviewed here. The SOS pathway is still the major paradigm of bacterial DNA damage response, and recent studies have clarified the mechanisms of SOS induction and key physiological roles of SOS including a very major role in genetic exchange and variation. When considering diverse bacteria, it is clear that SOS is not a uniform pathway with one purpose, but rather a platform that has evolved for differing functions in different bacteria. Relating in part to the SOS response, the field has uncovered multiple apparent cell-cycle checkpoints that assist cell survival after DNA damage and remarkable pathways that induce programmed cell death in bacteria. Bacterial DNA damage responses are also much broader than SOS, and several important examples of LexA-independent regulation will be reviewed. Finally, some recent advances that relate to the replication and repair of damaged DNA will be summarized. PMID:24097899

Multi-level damage identification with response reconstruction

NASA Astrophysics Data System (ADS)

Zhang, Chao-Dong; Xu, You-Lin

2017-10-01

Damage identification through finite element (FE) model updating usually forms an inverse problem. Solving the inverse identification problem for complex civil structures is very challenging since the dimension of potential damage parameters in a complex civil structure is often very large. Aside from enormous computation efforts needed in iterative updating, the ill-condition and non-global identifiability features of the inverse problem probably hinder the realization of model updating based damage identification for large civil structures. Following a divide-and-conquer strategy, a multi-level damage identification method is proposed in this paper. The entire structure is decomposed into several manageable substructures and each substructure is further condensed as a macro element using the component mode synthesis (CMS) technique. The damage identification is performed at two levels: the first is at macro element level to locate the potentially damaged region and the second is over the suspicious substructures to further locate as well as quantify the damage severity. In each level's identification, the damage searching space over which model updating is performed is notably narrowed down, not only reducing the computation amount but also increasing the damage identifiability. Besides, the Kalman filter-based response reconstruction is performed at the second level to reconstruct the response of the suspicious substructure for exact damage quantification. Numerical studies and laboratory tests are both conducted on a simply supported overhanging steel beam for conceptual verification. The results demonstrate that the proposed multi-level damage identification via response reconstruction does improve the identification accuracy of damage localization and quantization considerably.

Brain Connectivity in Pathological and Pharmacological Coma

PubMed Central

Noirhomme, Quentin; Soddu, Andrea; Lehembre, Rémy; Vanhaudenhuyse, Audrey; Boveroux, Pierre; Boly, Mélanie; Laureys, Steven

2010-01-01

Recent studies in patients with disorders of consciousness (DOC) tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the frontoparietal network. Functional neuroimaging studies have shown preserved albeit disconnected low-level cortical activation in response to external stimulation in patients in a “vegetative state” or unresponsive wakefulness syndrome. While activation of these “primary” sensory cortices does not necessarily reflect conscious awareness, activation in higher-order associative cortices in minimally conscious state patients seems to herald some residual perceptual awareness. PET studies have identified a metabolic dysfunction in a widespread frontoparietal “global neuronal workspace” in DOC patients including the midline default mode network (“intrinsic” system) and the lateral frontoparietal cortices or “extrinsic system.” Recent studies have investigated the relation of awareness to the functional connectivity within intrinsic and extrinsic networks, and with the thalami in both pathological and pharmacological coma. In brain damaged patients, connectivity in all default network areas was found to be non-linearly correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative, coma, and brain dead patients. Anesthesia-induced loss of consciousness was also shown to correlate with a global decrease in cortico-cortical and thalamo-cortical connectivity in both intrinsic and extrinsic networks, but not in auditory, or visual networks. In anesthesia, unconsciousness was also associated with a loss of cross-modal interactions between networks. These results suggest that conscious awareness critically depends on the functional integrity of thalamo-cortical and cortico-cortical frontoparietal connectivity within and between “intrinsic” and “extrinsic” brain networks. PMID:21191476

Detecting damage in full-scale honeycomb sandwich composite curved fuselage panels through frequency response

NASA Astrophysics Data System (ADS)

Leone, Frank A., Jr.; Ozevin, Didem; Mosinyi, Bao; Bakuckas, John G., Jr.; Awerbuch, Jonathan; Lau, Alan; Tan, Tein-Min

2008-03-01

Preliminary tests were conducted using frequency response (FR) characteristics to determine damage initiation and growth in a honeycomb sandwich graphite/epoxy curved panel. This investigation was part of a more general study investigating the damage tolerance characteristics of several such panels subjected to quasi-static internal pressurization combined with hoop and axial loading. The panels were tested at the Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility located at the Federal Aviation Administration William J. Hughes Technical Center in Atlantic City, NJ. The overall program objective was to investigate the damage tolerance characteristics of full-scale composite curved aircraft fuselage panels and the evolution of damage under quasi-static loading up to failure. This paper focuses on one aspect of this comprehensive investigation: the effect of state-of-damage on the characteristics of the frequency response of the subject material. The results presented herein show that recording the frequency response could be used for real-time monitoring of damage growth and in determining damage severity in full-scale composites fuselage aircraft structures.

RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage.

PubMed

Paul, Atanu; Wang, Bin

2017-05-18

Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX. We show that RNF8- and Ube2S-dependent Lys11-linkage ubiquitin conjugation plays an important role in regulating DNA damage-induced transcriptional silencing, distinct from the role of Lys63-linkage ubiquitin in the recruitment of DNA damage repair proteins 53BP1 and BRCA1. Thus, our study highlights the importance of linkage-specific ubiquitination at DNA damage sites, and it reveals that Lys11-linkage ubiquitin modification plays a crucial role in the DNA damage response. Copyright © 2017 Elsevier Inc. All rights reserved.

Extracellular magnesium enhances the damage to locomotor networks produced by metabolic perturbation mimicking spinal injury in the neonatal rat spinal cord in vitro.

PubMed

Margaryan, G; Mladinic, M; Mattioli, C; Nistri, A

2009-10-06

An acute injury to brain or spinal cord produces profound metabolic perturbation that extends and exacerbates tissue damage. Recent clinical interventions to treat this condition with i.v. Mg(2+) to stabilize its extracellular concentration provided disappointing results. The present study used an in vitro spinal cord model from the neonatal rat to investigate the role of extracellular Mg(2+) in the lesion evoked by a pathological medium mimicking the metabolic perturbation (hypoxia, aglycemia, oxidative stress, and acid pH) occurring in vivo. Damage was measured by taking as outcome locomotor network activity for up to 24 h after the primary insult. Pathological medium in 1 mM Mg(2+) solution (1 h) largely depressed spinal reflexes and suppressed fictive locomotion on the same and the following day. Conversely, pathological medium in either Mg(2+)-free or 5 mM Mg(2+) solution evoked temporary network depression and enabled fictive locomotion the day after. While global cell death was similar regardless of extracellular Mg(2+) solution, white matter was particularly affected. In ventral horn the number of surviving neurons was the highest in Mg(2+) free solution and the lowest in 1 mM Mg(2+), while motoneurons were unaffected. Although the excitotoxic damage elicited by kainate was insensitive to extracellular Mg(2+), 1 mM Mg(2+) potentiated the effect of combining pathological medium with kainate at low concentrations. These results indicate that preserving Mg(2+) homeostasis rendered experimental spinal injury more severe. Furthermore, analyzing ventral horn neuron numbers in relation to fictive locomotion expression might provide a first estimate of the minimal size of the functional locomotor network.

Chromosome territories reposition during DNA damage-repair response

PubMed Central

2013-01-01

Background Local higher-order chromatin structure, dynamics and composition of the DNA are known to determine double-strand break frequencies and the efficiency of repair. However, how DNA damage response affects the spatial organization of chromosome territories is still unexplored. Results Our report investigates the effect of DNA damage on the spatial organization of chromosome territories within interphase nuclei of human cells. We show that DNA damage induces a large-scale spatial repositioning of chromosome territories that are relatively gene dense. This response is dose dependent, and involves territories moving from the nuclear interior to the periphery and vice versa. Furthermore, we have found that chromosome territory repositioning is contingent upon double-strand break recognition and damage sensing. Importantly, our results suggest that this is a reversible process where, following repair, chromosome territories re-occupy positions similar to those in undamaged control cells. Conclusions Thus, our report for the first time highlights DNA damage-dependent spatial reorganization of whole chromosomes, which might be an integral aspect of cellular damage response. PMID:24330859

Accidental spills at sea--risk, impact, mitigation and the need for co-ordinated post-incident monitoring.

PubMed

Kirby, Mark F; Law, Robin J

2010-06-01

A fully integrated and effective response to an oil or chemical spill at sea must include a well planned and executed post-incident assessment of environmental contamination and damage. While salvage, rescue and clean-up operations are generally well considered, including reviews and exercises, the expertise, resources, networks and logistical planning required to achieve prompt and effective post-spill impact assessment and monitoring are not generally well established. The arrangement and co-ordination of post-incident monitoring and impact assessment need to consider sampling design, biological effects, chemical analysis and collection/interpretation of expert local knowledge. This paper discusses the risks, impacts and mitigation options associated with accidental spills and considers the importance of pre-considered impact assessment and monitoring programmes in the wider response cycle. The PREMIAM (Pollution Response in Emergencies: Marine Impact Assessment and Monitoring; www.premiam.org) project is considered as an example of an improved approach to the planning, co-ordination and conduct of post-incident monitoring.

Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent

PubMed Central

Song, Anren; Zhang, Yujin; Han, Leng; Yegutkin, Gennady G.; Liu, Hong; Sun, Kaiqi; D'Alessandro, Angelo; Li, Jessica; Karmouty-Quintana, Harry; Iriyama, Takayuki; Weng, Tingting; Zhao, Shushan; Wang, Wei; Wu, Hongyu; Nemkov, Travis; Subudhi, Andrew W.; Jameson-Van Houten, Sonja; Julian, Colleen G.; Lovering, Andrew T.; Hansen, Kirk C.; Zhang, Hong; Bogdanov, Mikhail; Dowhan, William; Jin, Jianping; Kellems, Rodney E.; Eltzschig, Holger K.; Blackburn, Michael; Roach, Robert C.; Xia, Yang

2017-01-01

Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response is unknown. We report that in healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent to high altitude and achieved even higher levels upon re-ascent, a feature that is positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) levels are reduced in humans at high altitude and in mice under hypoxia. eENT1 deletion allows rapid accumulation of plasma adenosine to counteract hypoxic tissue damage in mice. Adenosine signalling via erythrocyte ADORA2B induces PKA phosphorylation, ubiquitination and proteasomal degradation of eENT1. Reduced eENT1 resulting from initial hypoxia is maintained upon re-ascent in humans or re-exposure to hypoxia in mice and accounts for erythrocyte hypoxic memory and faster acclimatization. Our findings suggest that targeting identified purinergic-signalling network would enhance the hypoxia adenosine response to counteract hypoxia-induced maladaptation. PMID:28169986

LRRK2 interacts with ATM and regulates Mdm2-p53 cell proliferation axis in response to genotoxic stress.

PubMed

Chen, Zhongcan; Cao, Zhen; Zhang, Wei; Gu, Minxia; Zhou, Zhi Dong; Li, Baojie; Li, Jing; Tan, Eng King; Zeng, Li

2017-11-15

Pathogenic leucine-rich repeat kinase 2 (LRRK2) mutations are recognized as the most common cause of familial Parkinson's disease in certain populations. Recently, LRRK2 mutations were shown to be associated with a higher risk of hormone-related cancers. However, how LRRK2 itself contributes to cancer risk remains unknown. DNA damage causes cancer, and DNA damage responses are among the most important pathways in cancer biology. To understand the role of LRRK2 in DNA damage response pathway, we induced DNA damage by applying genotoxic stress to the cells with Adriamycin. We found that DNA damage enhances LRRK2 phosphorylation at Serine 910, Serine 935 and Serine 1292. We further showed that LRRK2 phosphorylation is abolished in the absence of ATM, suggesting that LRRK2 phosphorylation requires ATM. It should also be noted that LRRK2 interacts with ATM. In contrast, overexpression or knockdown of LRRK2 does not affect ATM phosphorylation, indicating that LRRK2 is the downstream target of ATM in response to DNA damage. Moreover, we demonstrated that LRRK2 increases the expression of p53 and p21 by increasing the Mdm2 phosphorylation in response to DNA damage. Loss-of-function in LRRK2 has the opposite effect to that of LRRK2. In addition, FACS analysis revealed that LRRK2 enhances cell cycle progression into S phase in response to DNA damage, a finding that was confirmed by 5-bromo-2'-deoxyuridine immunostaining. Taken together, our findings demonstrate that LRRK2 plays an important role in the ATM-Mdm2-p53 pathway that regulates cell proliferation in response to DNA damage. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response

PubMed Central

Xu, Ruijuan; Wang, Kai; Mileva, Izolda; Hannun, Yusuf A.; Obeid, Lina M.; Mao, Cungui

2016-01-01

Human cells respond to DNA damage by elevating sphingosine, a bioactive sphingolipid that induces programmed cell death (PCD) in response to various forms of stress, but its regulation and role in the DNA damage response remain obscure. Herein we demonstrate that DNA damage increases sphingosine levels in tumor cells by upregulating alkaline ceramidase 2 (ACER2) and that the upregulation of the ACER2/sphingosine pathway induces PCD in response to DNA damage by increasing the production of reactive oxygen species (ROS). Treatment with the DNA damaging agent doxorubicin increased both ACER2 expression and sphingosine levels in HCT116 cells in a dose-dependent manner. ACER2 overexpression increased sphingosine in HeLa cells whereas knocking down ACER2 inhibited the doxorubicin-induced increase in sphingosine in HCT116 cells, suggesting that DNA damage elevates sphingosine by upregulating ACER2. Knocking down ACER2 inhibited an increase in the apoptotic and necrotic cell population and the cleavage of poly ADP ribose polymerase (PARP) in HCT116 cells in response to doxorubicin as well as doxorubicin-induced release of lactate dehydrogenase (LDH) from these cells. Similar to treatment with doxorubicin, ACER2 overexpression induced an increase in the apoptotic and necrotic cell population and PARP cleavage in HeLa cells and LDH release from cells, suggesting that ACER2 upregulation mediates PCD in response to DNA damage through sphingosine. Mechanistic studies demonstrated that the upregulation of the ACER2/sphingosine pathway induces PCD by increasing ROS levels. Taken together, these results suggest that the ACER2/sphingosine pathway mediates PCD in response to DNA damage through ROS production. PMID:26943039

Cross-country transferability of multi-variable damage models

NASA Astrophysics Data System (ADS)

Wagenaar, Dennis; Lüdtke, Stefan; Kreibich, Heidi; Bouwer, Laurens

2017-04-01

Flood damage assessment is often done with simple damage curves based only on flood water depth. Additionally, damage models are often transferred in space and time, e.g. from region to region or from one flood event to another. Validation has shown that depth-damage curve estimates are associated with high uncertainties, particularly when applied in regions outside the area where the data for curve development was collected. Recently, progress has been made with multi-variable damage models created with data-mining techniques, i.e. Bayesian Networks and random forest. However, it is still unknown to what extent and under which conditions model transfers are possible and reliable. Model validations in different countries will provide valuable insights into the transferability of multi-variable damage models. In this study we compare multi-variable models developed on basis of flood damage datasets from Germany as well as from The Netherlands. Data from several German floods was collected using computer aided telephone interviews. Data from the 1993 Meuse flood in the Netherlands is available, based on compensations paid by the government. The Bayesian network and random forest based models are applied and validated in both countries on basis of the individual datasets. A major challenge was the harmonization of the variables between both datasets due to factors like differences in variable definitions, and regional and temporal differences in flood hazard and exposure characteristics. Results of model validations and comparisons in both countries are discussed, particularly in respect to encountered challenges and possible solutions for an improvement of model transferability.

Computationally-efficient stochastic cluster dynamics method for modeling damage accumulation in irradiated materials

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

Hoang, Tuan L.; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, CA 94550; Marian, Jaime, E-mail: jmarian@ucla.edu

2015-11-01

An improved version of a recently developed stochastic cluster dynamics (SCD) method (Marian and Bulatov, 2012) [6] is introduced as an alternative to rate theory (RT) methods for solving coupled ordinary differential equation (ODE) systems for irradiation damage simulations. SCD circumvents by design the curse of dimensionality of the variable space that renders traditional ODE-based RT approaches inefficient when handling complex defect population comprised of multiple (more than two) defect species. Several improvements introduced here enable efficient and accurate simulations of irradiated materials up to realistic (high) damage doses characteristic of next-generation nuclear systems. The first improvement is a proceduremore » for efficiently updating the defect reaction-network and event selection in the context of a dynamically expanding reaction-network. Next is a novel implementation of the τ-leaping method that speeds up SCD simulations by advancing the state of the reaction network in large time increments when appropriate. Lastly, a volume rescaling procedure is introduced to control the computational complexity of the expanding reaction-network through occasional reductions of the defect population while maintaining accurate statistics. The enhanced SCD method is then applied to model defect cluster accumulation in iron thin films subjected to triple ion-beam (Fe{sup 3+}, He{sup +} and H{sup +}) irradiations, for which standard RT or spatially-resolved kinetic Monte Carlo simulations are prohibitively expensive.« less

Computationally-efficient stochastic cluster dynamics method for modeling damage accumulation in irradiated materials

NASA Astrophysics Data System (ADS)

Hoang, Tuan L.; Marian, Jaime; Bulatov, Vasily V.; Hosemann, Peter

2015-11-01

An improved version of a recently developed stochastic cluster dynamics (SCD) method (Marian and Bulatov, 2012) [6] is introduced as an alternative to rate theory (RT) methods for solving coupled ordinary differential equation (ODE) systems for irradiation damage simulations. SCD circumvents by design the curse of dimensionality of the variable space that renders traditional ODE-based RT approaches inefficient when handling complex defect population comprised of multiple (more than two) defect species. Several improvements introduced here enable efficient and accurate simulations of irradiated materials up to realistic (high) damage doses characteristic of next-generation nuclear systems. The first improvement is a procedure for efficiently updating the defect reaction-network and event selection in the context of a dynamically expanding reaction-network. Next is a novel implementation of the τ-leaping method that speeds up SCD simulations by advancing the state of the reaction network in large time increments when appropriate. Lastly, a volume rescaling procedure is introduced to control the computational complexity of the expanding reaction-network through occasional reductions of the defect population while maintaining accurate statistics. The enhanced SCD method is then applied to model defect cluster accumulation in iron thin films subjected to triple ion-beam (Fe3+, He+ and H+) irradiations, for which standard RT or spatially-resolved kinetic Monte Carlo simulations are prohibitively expensive.

Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

PubMed Central

Kong, Eric F.; Tsui, Christina; Nguyen, M. Hong; Clancy, Cornelius J.; Fidel, Paul L.; Noverr, Mairi

2016-01-01

Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of Candida albicans, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably, C. albicans infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses. PMID:27430274

Size Effects in Impact Damage of Composite Sandwich Panels

NASA Technical Reports Server (NTRS)

Dobyns, Alan; Jackson, Wade

2003-01-01

Panel size has a large effect on the impact response and resultant damage level of honeycomb sandwich panels. It has been observed during impact testing that panels of the same design but different panel sizes will show large differences in damage when impacted with the same impact energy. To study this effect, a test program was conducted with instrumented impact testing of three different sizes of sandwich panels to obtain data on panel response and residual damage. In concert with the test program. a closed form analysis method was developed that incorporates the effects of damage on the impact response. This analysis method will predict both the impact response and the residual damage of a simply-supported sandwich panel impacted at any position on the panel. The damage is incorporated by the use of an experimental load-indentation curve obtained for the face-sheet/honeycomb and indentor combination under study. This curve inherently includes the damage response and can be obtained quasi-statically from a rigidly-backed specimen or a specimen with any support conditions. Good correlation has been obtained between the test data and the analysis results for the maximum force and residual indentation. The predictions can be improved by using a dynamic indentation curve. Analyses have also been done using the MSC/DYTRAN finite element code.

How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery

PubMed Central

Bordignon, Valentina; Trento, Elisabetta; D’Agosto, Giovanna; Cavallo, Ilaria; Pontone, Martina; Pimpinelli, Fulvia; Mariani, Luciano; Ensoli, Fabrizio

2017-01-01

The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM- and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)–STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses. PMID:29257060

Self-organizing hierarchies in sensor and communication networks.

PubMed

Prokopenko, Mikhail; Wang, Peter; Valencia, Philip; Price, Don; Foreman, Mark; Farmer, Anthony

2005-01-01

We consider a hierarchical multicellular sensing and communication network, embedded in an ageless aerospace vehicle that is expected to detect and react to multiple impacts and damage over a wide range of impact energies. In particular, we investigate self-organization of impact boundaries enclosing critically damaged areas, and impact networks connecting remote cells that have detected noncritical impacts. Each level of the hierarchy is shown to have distinct higher-order emergent properties, desirable in self-monitoring and self-repairing vehicles. In addition, cells and communication messages are shown to need memory (hysteresis) in order to retain desirable emergent behavior within and between various hierarchical levels. Spatiotemporal robustness of self-organizing hierarchies is quantitatively measured with graph-theoretic and information-theoretic techniques, such as the Shannon entropy. This allows us to clearly identify phase transitions separating chaotic dynamics from ordered and robust patterns.

Neural Network Burst Pressure Prediction in Composite Overwrapped Pressure Vessels

NASA Technical Reports Server (NTRS)

Hill, Eric v. K.; Dion, Seth-Andrew T.; Karl, Justin O.; Spivey, Nicholas S.; Walker, James L., II

2007-01-01

Acoustic emission data were collected during the hydroburst testing of eleven 15 inch diameter filament wound composite overwrapped pressure vessels. A neural network burst pressure prediction was generated from the resulting AE amplitude data. The bottles shared commonality of graphite fiber, epoxy resin, and cure time. Individual bottles varied by cure mode (rotisserie versus static oven curing), types of inflicted damage, temperature of the pressurant, and pressurization scheme. Three categorical variables were selected to represent undamaged bottles, impact damaged bottles, and bottles with lacerated hoop fibers. This categorization along with the removal of the AE data from the disbonding noise between the aluminum liner and the composite overwrap allowed the prediction of burst pressures in all three sets of bottles using a single backpropagation neural network. Here the worst case error was 3.38 percent.

Using Bayesian Network as a tool for coastal storm flood impact prediction at Varna Bay (Bulgaria, Western Black Sea)

NASA Astrophysics Data System (ADS)

Valchev, Nikolay; Eftimova, Petya; Andreeva, Nataliya; Prodanov, Bogdan

2017-04-01

Coastal zone is among the fastest evolving areas worldwide. Ever increasing population inhabiting coastal settlements develops often conflicting economic and societal activities. The existing imbalance between the expansion of these activities, on one hand, and the potential to accommodate them in a sustainable manner, on the other, becomes a critical problem. Concurrently, coasts are affected by various hydro-meteorological phenomena such as storm surges, heavy seas, strong winds and flash floods, which intensities and occurrence frequency is likely to increase due to the climate change. This implies elaboration of tools capable of quick prediction of impact of those phenomena on the coast and providing solutions in terms of disaster risk reduction measures. One such tool is Bayesian network. Proposed paper describes the set-up of such network for Varna Bay (Bulgaria, Western Black Sea). It relates near-shore storm conditions to their onshore flood potential and ultimately to relevant impact as relative damage on coastal and manmade environment. Methodology for set-up and training of the Bayesian network was developed within RISC-KIT project (Resilience-Increasing Strategies for Coasts - toolKIT). Proposed BN reflects the interaction between boundary conditions, receptors, hazard, and consequences. Storm boundary conditions - maximum significant wave height and peak surge level, were determined on the basis of their historical and projected occurrence. The only hazard considered in this study is flooding characterized by maximum inundation depth. BN was trained with synthetic events created by combining estimated boundary conditions. Flood impact was modeled with the process-based morphodynamical model XBeach. Restaurants, sport and leisure facilities, administrative buildings, and car parks were introduced in the network as receptors. Consequences (impact) are estimated in terms of relative damage caused by given inundation depth. National depth-damage (susceptibility) curves were used to define the percentage of damage ranked as low, moderate, high and very high. Besides previously described components, BN includes also two hazard influencing disaster risk reduction (DRR) measures: re-enforced embankment of Varna Port wall and beach nourishment. As a result of training process the network is able to evaluate spatially varying hazards and damages for specific storm conditions. Moreover, it is able to predict where on the site the highest impact would occur and to quantify the mitigation capacity of proposed DRR measures. For example, it is estimated that storm impact would be considerably reduced in present conditions but vulnerability would be still high in climate change perspective.

Investigating changes in brain network properties in HIV-associated neurocognitive disease (HAND) using mutual connectivity analysis (MCA)

NASA Astrophysics Data System (ADS)

Abidin, Anas Zainul; D'Souza, Adora M.; Nagarajan, Mahesh B.; Wismüller, Axel

2016-03-01

About 50% of subjects infected with HIV present deficits in cognitive domains, which are known collectively as HIV associated neurocognitive disorder (HAND). The underlying synaptodendritic damage can be captured using resting state functional MRI, as has been demonstrated by a few earlier studies. Such damage may induce topological changes of brain connectivity networks. We test this hypothesis by capturing the functional interdependence of 90 brain network nodes using a Mutual Connectivity Analysis (MCA) framework with non-linear time series modeling based on Generalized Radial Basis function (GRBF) neural networks. The network nodes are selected based on the regions defined in the Automated Anatomic Labeling (AAL) atlas. Each node is represented by the average time series of the voxels of that region. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We tested for differences in these properties in network graphs obtained for 10 subjects (6 male and 4 female, 5 HIV+ and 5 HIV-). Global network properties captured some differences between these subject cohorts, though significant differences were seen only with the clustering coefficient measure. Local network properties, such as local efficiency and the degree of connections, captured significant differences in regions of the frontal lobe, precentral and cingulate cortex amongst a few others. These results suggest that our method can be used to effectively capture differences occurring in brain network connectivity properties revealed by resting-state functional MRI in neurological disease states, such as HAND.

DNAtraffic--a new database for systems biology of DNA dynamics during the cell life.

PubMed

Kuchta, Krzysztof; Barszcz, Daniela; Grzesiuk, Elzbieta; Pomorski, Pawel; Krwawicz, Joanna

2012-01-01

DNAtraffic (http://dnatraffic.ibb.waw.pl/) is dedicated to be a unique comprehensive and richly annotated database of genome dynamics during the cell life. It contains extensive data on the nomenclature, ontology, structure and function of proteins related to the DNA integrity mechanisms such as chromatin remodeling, histone modifications, DNA repair and damage response from eight organisms: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Escherichia coli and Arabidopsis thaliana. DNAtraffic contains comprehensive information on the diseases related to the assembled human proteins. DNAtraffic is richly annotated in the systemic information on the nomenclature, chemistry and structure of DNA damage and their sources, including environmental agents or commonly used drugs targeting nucleic acids and/or proteins involved in the maintenance of genome stability. One of the DNAtraffic database aim is to create the first platform of the combinatorial complexity of DNA network analysis. Database includes illustrations of pathways, damage, proteins and drugs. Since DNAtraffic is designed to cover a broad spectrum of scientific disciplines, it has to be extensively linked to numerous external data sources. Our database represents the result of the manual annotation work aimed at making the DNAtraffic much more useful for a wide range of systems biology applications.

DNAtraffic—a new database for systems biology of DNA dynamics during the cell life

PubMed Central

Kuchta, Krzysztof; Barszcz, Daniela; Grzesiuk, Elzbieta; Pomorski, Pawel; Krwawicz, Joanna

2012-01-01

DNAtraffic (http://dnatraffic.ibb.waw.pl/) is dedicated to be a unique comprehensive and richly annotated database of genome dynamics during the cell life. It contains extensive data on the nomenclature, ontology, structure and function of proteins related to the DNA integrity mechanisms such as chromatin remodeling, histone modifications, DNA repair and damage response from eight organisms: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Escherichia coli and Arabidopsis thaliana. DNAtraffic contains comprehensive information on the diseases related to the assembled human proteins. DNAtraffic is richly annotated in the systemic information on the nomenclature, chemistry and structure of DNA damage and their sources, including environmental agents or commonly used drugs targeting nucleic acids and/or proteins involved in the maintenance of genome stability. One of the DNAtraffic database aim is to create the first platform of the combinatorial complexity of DNA network analysis. Database includes illustrations of pathways, damage, proteins and drugs. Since DNAtraffic is designed to cover a broad spectrum of scientific disciplines, it has to be extensively linked to numerous external data sources. Our database represents the result of the manual annotation work aimed at making the DNAtraffic much more useful for a wide range of systems biology applications. PMID:22110027

Development and Evaluation of Sensor Concepts for Ageless Aerospace Vehicles: Report 5 - Phase 2 Implementation of the Concept Demonstrator

NASA Technical Reports Server (NTRS)

Batten, Adam; Dunlop, John; Edwards, Graeme; Farmer, Tony; Gaffney, Bruce; Hedley, Mark; Hoschke, Nigel; Isaacs, Peter; Johnson, Mark; Lewis, Chris;

Disruption of a Regulatory Network Consisting of Neutrophils and Platelets Fosters Persisting Inflammation in Rheumatic Diseases.

PubMed

Maugeri, Norma; Rovere-Querini, Patrizia; Manfredi, Angelo A

2016-01-01

A network of cellular interactions that involve blood leukocytes and platelets maintains vessel homeostasis. It plays a critical role in the response to invading microbes by recruiting intravascular immunity and through the generation of neutrophil extracellular traps (NETs) and immunothrombosis. Moreover, it enables immune cells to respond to remote chemoattractants by crossing the endothelial barrier and reaching sites of infection. Once the network operating under physiological conditions is disrupted, the reciprocal activation of cells in the blood and the vessel walls determines the vascular remodeling via inflammatory signals delivered to stem/progenitor cells. A deregulated leukocyte/mural cell interaction is an early critical event in the natural history of systemic inflammation. Despite intense efforts, the signals that initiate and sustain the immune-mediated vessel injury, or those that enforce the often-prolonged phases of clinical quiescence in patients with vasculitis, have only been partially elucidated. Here, we discuss recent evidence that implicates the prototypic damage-associated molecular pattern/alarmin, the high mobility group box 1 (HMGB1) protein in systemic vasculitis and in the vascular inflammation associated with systemic sclerosis. HMGB1 could represent a player in the pathogenesis of rheumatic diseases and an attractive target for molecular interventions.

Structural Health Management of Damaged Aircraft Structures Using the Digital Twin Concept

NASA Technical Reports Server (NTRS)

Seshadri, Banavara R.; Krishnamurthy, Thiagarajan

2017-01-01

The development of multidisciplinary integrated Structural Health Management (SHM) tools will enable accurate detection, and prognosis of damaged aircraft under normal and adverse conditions during flight. As part of the digital twin concept, methodologies are developed by using integrated multiphysics models, sensor information and input data from an in-service vehicle to mirror and predict the life of its corresponding physical twin. SHM tools are necessary for both damage diagnostics and prognostics for continued safe operation of damaged aircraft structures. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and structural damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign object impact that can reach a critical size during flight, resulting in loss of control of the aircraft. To avoid unstable, catastrophic propagation of damage during a flight, load levels must be maintained that are below a reduced load-carrying capacity for continued safe operation of an aircraft. Hence, a capability is needed for accurate real-time predictions of damage size and safe load carrying capacity for structures with complex damage configurations. In the present work, a procedure is developed that uses guided wave responses to interrogate damage. As the guided wave interacts with damage, the signal attenuates in some directions and reflects in others. This results in a difference in signal magnitude as well as phase shifts between signal responses for damaged and undamaged structures. Accurate estimation of damage size, location, and orientation is made by evaluating the cumulative signal responses at various pre-selected sensor locations using a genetic algorithm (GA) based optimization procedure. The damage size, location, and orientation is obtained by minimizing the difference between the reference responses and the responses obtained by wave propagation finite element analysis of different representative cracks, geometries, and sizes.

Quantitative proteomics and dynamic imaging of the nucleolus reveal distinct responses to UV and ionizing radiation.

PubMed

Moore, Henna M; Bai, Baoyan; Boisvert, François-Michel; Latonen, Leena; Rantanen, Ville; Simpson, Jeremy C; Pepperkok, Rainer; Lamond, Angus I; Laiho, Marikki

2011-10-01

The nucleolus is a nuclear organelle that coordinates rRNA transcription and ribosome subunit biogenesis. Recent proteomic analyses have shown that the nucleolus contains proteins involved in cell cycle control, DNA processing and DNA damage response and repair, in addition to the many proteins connected with ribosome subunit production. Here we study the dynamics of nucleolar protein responses in cells exposed to stress and DNA damage caused by ionizing and ultraviolet (UV) radiation in diploid human fibroblasts. We show using a combination of imaging and quantitative proteomics methods that nucleolar substructure and the nucleolar proteome undergo selective reorganization in response to UV damage. The proteomic responses to UV include alterations of functional protein complexes such as the SSU processome and exosome, and paraspeckle proteins, involving both decreases and increases in steady state protein ratios, respectively. Several nonhomologous end-joining proteins (NHEJ), such as Ku70/80, display similar fast responses to UV. In contrast, nucleolar proteomic responses to IR are both temporally and spatially distinct from those caused by UV, and more limited in terms of magnitude. With the exception of the NHEJ and paraspeckle proteins, where IR induces rapid and transient changes within 15 min of the damage, IR does not alter the ratios of most other functional nucleolar protein complexes. The rapid transient decrease of NHEJ proteins in the nucleolus indicates that it may reflect a response to DNA damage. Our results underline that the nucleolus is a specific stress response organelle that responds to different damage and stress agents in a unique, damage-specific manner.

Damage Detection/Locating System Providing Thermal Protection

NASA Technical Reports Server (NTRS)

Woodard, Stanley E. (Inventor); Jones, Thomas W. (Inventor); Taylor, Bryant D. (Inventor); Qamar, A. Shams (Inventor)

2010-01-01

A damage locating system also provides thermal protection. An array of sensors substantially tiles an area of interest. Each sensor is a reflective-surface conductor having operatively coupled inductance and capacitance. A magnetic field response recorder is provided to interrogate each sensor before and after a damage condition. Changes in response are indicative of damage and a corresponding location thereof.

Detection of Hail Storms in Radar Imagery Using Deep Learning

NASA Technical Reports Server (NTRS)

Pullman, Melinda; Gurung, Iksha; Ramachandran, Rahul; Maskey, Manil

2017-01-01

In 2016, hail was responsible for 3.5 billion and 23 million dollars in damage to property and crops, respectively, making it the second costliest weather phenomenon in the United States. In an effort to improve hail-prediction techniques and reduce the societal impacts associated with hail storms, we propose a deep learning technique that leverages radar imagery for automatic detection of hail storms. The technique is applied to radar imagery from 2011 to 2016 for the contiguous United States and achieved a precision of 0.848. Hail storms are primarily detected through the visual interpretation of radar imagery (Mrozet al., 2017). With radars providing data every two minutes, the detection of hail storms has become a big data task. As a result, scientists have turned to neural networks that employ computer vision to identify hail-bearing storms (Marzbanet al., 2001). In this study, we propose a deep Convolutional Neural Network (ConvNet) to understand the spatial features and patterns of radar echoes for detecting hailstorms.

Conditional repair by locally switching the thermal healing capability of dynamic covalent polymers with light

PubMed Central

Fuhrmann, Anne; Göstl, Robert; Wendt, Robert; Kötteritzsch, Julia; Hager, Martin D.; Schubert, Ulrich S.; Brademann-Jock, Kerstin; Thünemann, Andreas F.; Nöchel, Ulrich; Behl, Marc; Hecht, Stefan

2016-01-01

Healable materials could play an important role in reducing the environmental footprint of our modern technological society through extending the life cycles of consumer products and constructions. However, as most healing processes are carried out by heat alone, the ability to heal damage generally kills the parent material's thermal and mechanical properties. Here we present a dynamic covalent polymer network whose thermal healing ability can be switched ‘on' and ‘off' on demand by light, thereby providing local control over repair while retaining the advantageous macroscopic properties of static polymer networks. We employ a photoswitchable furan-based crosslinker, which reacts with short and mobile maleimide-substituted poly(lauryl methacrylate) chains forming strong covalent bonds while simultaneously allowing the reversible, spatiotemporally resolved control over thermally induced de- and re-crosslinking. We reason that our system can be adapted to more complex materials and has the potential to impact applications in responsive coatings, photolithography and microfabrication. PMID:27941924

Spike-timing-dependent plasticity in the human dorso-lateral prefrontal cortex.

PubMed

Casula, Elias Paolo; Pellicciari, Maria Concetta; Picazio, Silvia; Caltagirone, Carlo; Koch, Giacomo

2016-12-01

Changes in the synaptic strength of neural connections are induced by repeated coupling of activity of interconnected neurons with precise timing, a phenomenon known as spike-timing-dependent plasticity (STDP). It is debated if this mechanism exists in large-scale cortical networks in humans. We combined transcranial magnetic stimulation (TMS) with concurrent electroencephalography (EEG) to directly investigate the effects of two paired associative stimulation (PAS) protocols (fronto-parietal and parieto-frontal) of pre and post-synaptic inputs within the human fronto-parietal network. We found evidence that the dorsolateral prefrontal cortex (DLPFC) has the potential to form robust STDP. Long-term potentiation/depression of TMS-evoked cortical activity is prompted after that DLPFC stimulation is followed/preceded by posterior parietal stimulation. Such bidirectional changes are paralleled by sustained increase/decrease of high-frequency oscillatory activity, likely reflecting STDP responsivity. The current findings could be important to drive plasticity of damaged cortical circuits in patients with cognitive or psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Conditional repair by locally switching the thermal healing capability of dynamic covalent polymers with light

NASA Astrophysics Data System (ADS)

Fuhrmann, Anne; Göstl, Robert; Wendt, Robert; Kötteritzsch, Julia; Hager, Martin D.; Schubert, Ulrich S.; Brademann-Jock, Kerstin; Thünemann, Andreas F.; Nöchel, Ulrich; Behl, Marc; Hecht, Stefan

2016-12-01

Healable materials could play an important role in reducing the environmental footprint of our modern technological society through extending the life cycles of consumer products and constructions. However, as most healing processes are carried out by heat alone, the ability to heal damage generally kills the parent material's thermal and mechanical properties. Here we present a dynamic covalent polymer network whose thermal healing ability can be switched `on' and `off' on demand by light, thereby providing local control over repair while retaining the advantageous macroscopic properties of static polymer networks. We employ a photoswitchable furan-based crosslinker, which reacts with short and mobile maleimide-substituted poly(lauryl methacrylate) chains forming strong covalent bonds while simultaneously allowing the reversible, spatiotemporally resolved control over thermally induced de- and re-crosslinking. We reason that our system can be adapted to more complex materials and has the potential to impact applications in responsive coatings, photolithography and microfabrication.

Helicopter rotor blade frequency evolution with damage growth and signal processing

NASA Astrophysics Data System (ADS)

Roy, Niranjan; Ganguli, Ranjan

2005-05-01

Structural damage in materials evolves over time due to growth of fatigue cracks in homogenous materials and a complicated process of matrix cracking, delamination, fiber breakage and fiber matrix debonding in composite materials. In this study, a finite element model of the helicopter rotor blade is used to analyze the effect of damage growth on the modal frequencies in a qualitative manner. Phenomenological models of material degradation for homogenous and composite materials are used. Results show that damage can be detected by monitoring changes in lower as well as higher mode flap (out-of-plane bending), lag (in-plane bending) and torsion rotating frequencies, especially for composite materials where the onset of the last stage of damage of fiber breakage is most critical. Curve fits are also proposed for mathematical modeling of the relationship between rotating frequencies and cycles. Finally, since operational data are noisy and also contaminated with outliers, denoising algorithms based on recursive median filters and radial basis function neural networks and wavelets are studied and compared with a moving average filter using simulated data for improved health-monitoring application. A novel recursive median filter is designed using integer programming through genetic algorithm and is found to have comparable performance to neural networks with much less complexity and is better than wavelet denoising for outlier removal. This filter is proposed as a tool for denoising time series of damage indicators.

The Molecular Origin of the MMR-dependent Apoptosis Pathway from Dynamics Analysis of MutSα-DNA Complexes

PubMed Central

Negureanu, Lacramioara; Salsbury, Freddie R.

2012-01-01

The cellular response to DNA damage signaling by MMR proteins is incompletely understood. It is generally accepted that MMR-dependent apoptosis pathway in response to DNA damage detection is independent of MMR's DNA repair function. In this study we investigate correlated motions in response to the binding of mismatched and PCL DNA fragments by MutSα, as derived from 50 ns molecular dynamics simulations. The protein dynamics in response to the mismatched and damaged DNA recognition suggests that MutSα signals their recognition through independent pathways providing evidence for the molecular origin of the MMR-dependent apoptosis. MSH2 subunit is indicated to play a key role in signaling both mismatched and damaged DNA recognition; localized and collective motions within the protein allow identifying sites on the MSH2 surface possible involved in recruiting proteins responsible for downstream events. Unlike in the mismatch complex, predicted key communication sites specific for the damage recognition are on the list of known cancer causing mutations or deletions. This confirms MSH2's role in signaling DNA-damage induced apoptosis and suggests that defects in MMR alone is sufficient to trigger tumorigenesis, supporting the experimental evidence that MMR-damage response function could protect from the early occurrence of tumors. Identifying these particular communication sites may have implications for the treatment of cancers that are not defective for MMR, but are unable to function optimally for MMR-dependent responses following DNA damage such as the case of resistance to cisplatin. PMID:22712459

Pressurized vascular systems for self-healing materials

PubMed Central

Hamilton, A. R.; Sottos, N. R.; White, S. R.

2012-01-01

An emerging strategy for creating self-healing materials relies on embedded vascular networks of microchannels to transport reactive fluids to regions of damage. Here we investigate the use of active pumping for the pressurized delivery of a two-part healing system, allowing a small vascular system to deliver large volumes of healing agent. Different pumping strategies are explored to improve the mixing and subsequent polymerization of healing agents in the damage zone. Significant improvements in the number of healing cycles and in the overall healing efficiency are achieved compared with prior passive schemes that use only capillary forces for the delivery of healing agents. At the same time, the volume of the vascular system required to achieve this superior healing performance is significantly reduced. In the best case, nearly full recovery of fracture toughness is attained throughout 15 cycles of damage and healing, with a vascular network constituting just 0.1 vol% of the specimen. PMID:21957119

Surrogate Modeling of High-Fidelity Fracture Simulations for Real-Time Residual Strength Predictions

NASA Technical Reports Server (NTRS)

Spear, Ashley D.; Priest, Amanda R.; Veilleux, Michael G.; Ingraffea, Anthony R.; Hochhalter, Jacob D.

2011-01-01

A surrogate model methodology is described for predicting in real time the residual strength of flight structures with discrete-source damage. Starting with design of experiment, an artificial neural network is developed that takes as input discrete-source damage parameters and outputs a prediction of the structural residual strength. Target residual strength values used to train the artificial neural network are derived from 3D finite element-based fracture simulations. A residual strength test of a metallic, integrally-stiffened panel is simulated to show that crack growth and residual strength are determined more accurately in discrete-source damage cases by using an elastic-plastic fracture framework rather than a linear-elastic fracture mechanics-based method. Improving accuracy of the residual strength training data would, in turn, improve accuracy of the surrogate model. When combined, the surrogate model methodology and high-fidelity fracture simulation framework provide useful tools for adaptive flight technology.

Surrogate Modeling of High-Fidelity Fracture Simulations for Real-Time Residual Strength Predictions

NASA Technical Reports Server (NTRS)

Spear, Ashley D.; Priest, Amanda R.; Veilleux, Michael G.; Ingraffea, Anthony R.; Hochhalter, Jacob D.

2011-01-01

A surrogate model methodology is described for predicting, during flight, the residual strength of aircraft structures that sustain discrete-source damage. Starting with design of experiment, an artificial neural network is developed that takes as input discrete-source damage parameters and outputs a prediction of the structural residual strength. Target residual strength values used to train the artificial neural network are derived from 3D finite element-based fracture simulations. Two ductile fracture simulations are presented to show that crack growth and residual strength are determined more accurately in discrete-source damage cases by using an elastic-plastic fracture framework rather than a linear-elastic fracture mechanics-based method. Improving accuracy of the residual strength training data does, in turn, improve accuracy of the surrogate model. When combined, the surrogate model methodology and high fidelity fracture simulation framework provide useful tools for adaptive flight technology.

The Extraction of Post-Earthquake Building Damage Informatiom Based on Convolutional Neural Network

NASA Astrophysics Data System (ADS)

Chen, M.; Wang, X.; Dou, A.; Wu, X.

2018-04-01

The seismic damage information of buildings extracted from remote sensing (RS) imagery is meaningful for supporting relief and effective reduction of losses caused by earthquake. Both traditional pixel-based and object-oriented methods have some shortcoming in extracting information of object. Pixel-based method can't make fully use of contextual information of objects. Object-oriented method faces problem that segmentation of image is not ideal, and the choice of feature space is difficult. In this paper, a new stratage is proposed which combines Convolution Neural Network (CNN) with imagery segmentation to extract building damage information from remote sensing imagery. the key idea of this method includes two steps. First to use CNN to predicate the probability of each pixel and then integrate the probability within each segmentation spot. The method is tested through extracting the collapsed building and uncollapsed building from the aerial image which is acquired in Longtoushan Town after Ms 6.5 Ludian County, Yunnan Province earthquake. The results show that the proposed method indicates its effectiveness in extracting damage information of buildings after earthquake.

Effects of Displacement Damage on the Time-Resolved Gain and Bandwidth of a Low Breakdown Voltage Si Avalanche Photodiode

NASA Technical Reports Server (NTRS)

Laird, Jamie S.; Onoda, Shinobu; Hirao, Toshio; Becker, Heidi; Johnston, Allan; Laird, Jamie S.; Itoh, Hisayoshi

2006-01-01

Effects of displacement damage and ionization damage induced by gamma irradiation on the dark current and impulse response of a high-bandwidth low breakdown voltage Si Avalanche Photodiode has been investigated using picosecond laser microscopy. At doses as high as 10Mrad (Si) minimal alteration in the impulse response and bandwidth were observed. However, dark current measurements also performed with and without biased irradiation exhibit anomalously large damage factors for applied biases close to breakdown. The absence of any degradation in the impulse response is discussed as are possible mechanisms for higher dark current damage factors observed for biased irradiation.

Destabilization of the MutSα’s protein-protein interface due to binding to the DNA adduct induced by anticancer agent Carboplatin via molecular dynamics simulations

PubMed Central

Negureanu, Lacramioara; Salsbury, Freddie R

2013-01-01

DNA mismatch repair (MMR) proteins maintain genetic integrity in all organisms by recognizing and repairing DNA errors. Such alteration of hereditary information can lead to various diseases, including cancer. Besides their role in DNA repair, MMR proteins detect and initiate cellular responses to certain type of DNA damage. Its response to the damaged DNA has made the human MMR pathway a useful target for anticancer agents such as carboplatin. This study indicates that strong, specific interactions at the interface of MutSα in response to the mismatched DNA recognition are replaced by weak, non-specific interactions in response to the damaged DNA recognition. Data suggest a severe impairment of the dimerization of MutSα in response to the damaged DNA recognition. While the core of MutSα is preserved in response to the damaged DNA recognition, the loss of contact surface and the rearrangement of contacts at the protein interface suggest a different packing in response to the damaged DNA recognition. Coupled in response to the mismatched DNA recognition, interaction energies, hydrogen bonds, salt bridges, and solvent accessible surface areas at the interface of MutSα and within the subunits are uncoupled or asynchronously coupled in response to the damaged DNA recognition. These pieces of evidence suggest that the loss of a synchronous mode of response in the MutSα’s surveillance for DNA errors would possible be one of the mechanism(s) of signaling the MMR-dependent programed cell death much wanted in anticancer therapies. The analysis was drawn from dynamics simulations. PMID:24061854

Uninformative memories will prevail: the storage of correlated representations and its consequences.

PubMed

Kropff, Emilio; Treves, Alessandro

2007-11-01

Autoassociative networks were proposed in the 80's as simplified models of memory function in the brain, using recurrent connectivity with Hebbian plasticity to store patterns of neural activity that can be later recalled. This type of computation has been suggested to take place in the CA3 region of the hippocampus and at several levels in the cortex. One of the weaknesses of these models is their apparent inability to store correlated patterns of activity. We show, however, that a small and biologically plausible modification in the "learning rule" (associating to each neuron a plasticity threshold that reflects its popularity) enables the network to handle correlations. We study the stability properties of the resulting memories (in terms of their resistance to the damage of neurons or synapses), finding a novel property of autoassociative networks: not all memories are equally robust, and the most informative are also the most sensitive to damage. We relate these results to category-specific effects in semantic memory patients, where concepts related to "non-living things" are usually more resistant to brain damage than those related to "living things," a phenomenon suspected to be rooted in the correlation between representations of concepts in the cortex.

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

PubMed

Spieth, Peter M; Carvalho, Alysson R; Pelosi, Paolo; Hoehn, Catharina; Meissner, Christoph; Kasper, Michael; Hübler, Matthias; von Neindorff, Matthias; Dassow, Constanze; Barrenschee, Martina; Uhlig, Stefan; Koch, Thea; de Abreu, Marcelo Gama

2009-04-15

Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Intelligent Modeling for Nuclear Power Plant Accident Management

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

Darling, Michael Christropher; Luger, George F.; Jones, Thomas B.

This study explores the viability of using counterfactual reasoning for impact analyses when understanding and responding to “beyond-design-basis” nuclear power plant accidents. Currently, when a severe nuclear power plant accident occurs, plant operators rely on Severe Accident Management Guidelines. However, the current guidelines are limited in scope and depth: for certain types of accidents, plant operators would have to work to mitigate the damage with limited experience and guidance for the particular situation. We aim to fill the need for comprehensive accident support by using a dynamic Bayesian network to aid in the diagnosis of a nuclear reactor’s state andmore » to analyze the impact of possible response measures.« less

Intelligent Modeling for Nuclear Power Plant Accident Management

DOE PAGES

Darling, Michael Christropher; Luger, George F.; Jones, Thomas B.; ...

2018-03-29

This study explores the viability of using counterfactual reasoning for impact analyses when understanding and responding to “beyond-design-basis” nuclear power plant accidents. Currently, when a severe nuclear power plant accident occurs, plant operators rely on Severe Accident Management Guidelines. However, the current guidelines are limited in scope and depth: for certain types of accidents, plant operators would have to work to mitigate the damage with limited experience and guidance for the particular situation. We aim to fill the need for comprehensive accident support by using a dynamic Bayesian network to aid in the diagnosis of a nuclear reactor’s state andmore » to analyze the impact of possible response measures.« less

The human intra-S checkpoint response to UVC-induced DNA damage.

PubMed

Kaufmann, William K

2010-05-01

The intra-S checkpoint response to 254 nm light (UVC)-induced DNA damage appears to have dual functions to slow the rate of DNA synthesis and stabilize replication forks that become stalled at sites of UVC-induced photoproducts in DNA. These functions should provide more time for repair of damaged DNA before its replication and thereby reduce the frequencies of mutations and chromosomal aberrations in surviving cells. This review tries to summarize the history of discovery of the checkpoint, the current state of understanding of the biological features of intra-S checkpoint signaling and its mechanisms of action with a focus primarily on intra-S checkpoint responses in human cells. The differences in the intra-S checkpoint responses to UVC and ionizing radiation-induced DNA damage are emphasized. Evidence that [6-4]pyrimidine-pyrimidone photoproducts in DNA trigger the response is discussed and the relationships between cellular responses to UVC and the molecular dose of UVC-induced DNA damage are briefly summarized. The role of the intra-S checkpoint response in protecting against solar radiation carcinogenesis remains to be determined.

Snm1B/Apollo functions in the Fanconi anemia pathway in response to DNA interstrand crosslinks.

PubMed

Mason, Jennifer M; Sekiguchi, JoAnn M

2011-07-01

Fanconi anemia (FA) is an inherited chromosomal instability disorder characterized by childhood aplastic anemia, developmental abnormalities and cancer predisposition. One of the hallmark phenotypes of FA is cellular hypersensitivity to agents that induce DNA interstrand crosslinks (ICLs), such as mitomycin C (MMC). FA is caused by mutation in at least 14 genes which function in the resolution of ICLs during replication. The FA proteins act within the context of a protein network in coordination with multiple repair factors that function in distinct pathways. SNM1B/Apollo is a member of metallo-β-lactamase/βCASP family of nucleases and has been demonstrated to function in ICL repair. However, the relationship between SNM1B and the FA protein network is not known. In the current study, we establish that SNM1B functions epistatically to the central FA factor, FANCD2, in cellular survival after ICL damage and homology-directed repair of DNA double-strand breaks. We also demonstrate that MMC-induced chromosomal anomalies are increased in SNM1B-depleted cells, and this phenotype is not further exacerbated upon depletion of either FANCD2 or another key FA protein, FANCI. Furthermore, we find that SNM1B is required for proper localization of critical repair factors, including FANCD2, BRCA1 and RAD51, to MMC-induced subnuclear foci. Our findings demonstrate that SNM1B functions within the FA pathway during the repair of ICL damage.

Heterogeneity in the Fault Damage Zone: a Field Study on the Borrego Fault, B.C., Mexico

NASA Astrophysics Data System (ADS)

Ostermeijer, G.; Mitchell, T. M.; Dorsey, M. T.; Browning, J.; Rockwell, T. K.; Aben, F. M.; Fletcher, J. M.; Brantut, N.

2017-12-01

The nature and distribution of damage around faults, and its impacts on fault zone properties has been a hot topic of research over the past decade. Understanding the mechanisms that control the formation of off fault damage can shed light on the processes during the seismic cycle, and the nature of fault zone development. Recent published work has identified three broad zones of damage around most faults based on the type, intensity, and extent of fracturing; Tip, Wall, and Linking damage. Although these zones are able to adequately characterise the general distribution of damage, little has been done to identify the nature of damage heterogeneity within those zones, often simplifying the distribution to fit log-normal linear decay trends. Here, we attempt to characterise the distribution of fractures that make up the wall damage around seismogenic faults. To do so, we investigate an extensive two dimensional fracture network exposed on a river cut platform along the Borrego Fault, BC, Mexico, 5m wide, and extending 20m from the fault core into the damage zone. High resolution fracture mapping of the outcrop, covering scales ranging three orders of magnitude (cm to m), has allowed for detailed observations of the 2D damage distribution within the fault damage zone. Damage profiles were obtained along several 1D transects perpendicular to the fault and micro-damage was examined from thin-sections at various locations around the outcrop for comparison. Analysis of the resulting fracture network indicates heterogeneities in damage intensity at decimetre scales resulting from a patchy distribution of high and low intensity corridors and clusters. Such patchiness may contribute to inconsistencies in damage zone widths defined along 1D transects and the observed variability of fracture densities around decay trends. How this distribution develops with fault maturity and the scaling of heterogeneities above and below the observed range will likely play a key role in understanding the evolution of fault damage, it's feedback into the seismic cycle, and impact on fluid migration in fault zones. The dataset from the Borrego Fault offers a unique opportunity to study the distribution of fault damage in-situ, and provide field observations towards improving fault zone models.

Structural Health Monitoring in Composite Structures by Fiber-Optic Sensors.

PubMed

Güemes, Alfredo; Fernández-López, Antonio; F Díaz-Maroto, Patricia; Lozano, Angel; Sierra-Perez, Julian

2018-04-04

Fiber-optic sensors cannot measure damage; to get information about damage from strain measurements, additional strategies are needed, and several alternatives are available in the existing literature. This paper discusses two independent procedures. The first is based on detecting new strains appearing around a damage spot. The structure does not need to be under loads, the technique is very robust, and damage detectability is high, but it requires sensors to be located very close to the damage, so it is a local technique. The second approach offers wider coverage of the structure; it is based on identifying the changes caused by damage on the strain field in the whole structure for similar external loads. Damage location does not need to be known a priori, and detectability is dependent upon the sensor's network density, the damage size, and the external loads. Examples of application to real structures are given.

Structural Health Monitoring in Composite Structures by Fiber-Optic Sensors †

PubMed Central

Güemes, Alfredo; Díaz-Maroto, Patricia F.; Lozano, Angel; Sierra-Perez, Julian

2018-01-01

Fiber-optic sensors cannot measure damage; to get information about damage from strain measurements, additional strategies are needed, and several alternatives are available in the existing literature. This paper discusses two independent procedures. The first is based on detecting new strains appearing around a damage spot. The structure does not need to be under loads, the technique is very robust, and damage detectability is high, but it requires sensors to be located very close to the damage, so it is a local technique. The second approach offers wider coverage of the structure; it is based on identifying the changes caused by damage on the strain field in the whole structure for similar external loads. Damage location does not need to be known a priori, and detectability is dependent upon the sensor’s network density, the damage size, and the external loads. Examples of application to real structures are given. PMID:29617345

Selected Flight Test Results for Online Learning Neural Network-Based Flight Control System

NASA Technical Reports Server (NTRS)

Williams, Peggy S.

2004-01-01

The NASA F-15 Intelligent Flight Control System project team has developed a series of flight control concepts designed to demonstrate the benefits of a neural network-based adaptive controller. The objective of the team is to develop and flight-test control systems that use neural network technology to optimize the performance of the aircraft under nominal conditions as well as stabilize the aircraft under failure conditions. Failure conditions include locked or failed control surfaces as well as unforeseen damage that might occur to the aircraft in flight. This report presents flight-test results for an adaptive controller using stability and control derivative values from an online learning neural network. A dynamic cell structure neural network is used in conjunction with a real-time parameter identification algorithm to estimate aerodynamic stability and control derivative increments to the baseline aerodynamic derivatives in flight. This set of open-loop flight tests was performed in preparation for a future phase of flights in which the learning neural network and parameter identification algorithm output would provide the flight controller with aerodynamic stability and control derivative updates in near real time. Two flight maneuvers are analyzed a pitch frequency sweep and an automated flight-test maneuver designed to optimally excite the parameter identification algorithm in all axes. Frequency responses generated from flight data are compared to those obtained from nonlinear simulation runs. An examination of flight data shows that addition of the flight-identified aerodynamic derivative increments into the simulation improved the pitch handling qualities of the aircraft.

Hydromechanical modeling of clay rock including fracture damage

NASA Astrophysics Data System (ADS)

Asahina, D.; Houseworth, J. E.; Birkholzer, J. T.

2012-12-01

Argillaceous rock typically acts as a flow barrier, but under certain conditions significant and potentially conductive fractures may be present. Fracture formation is well-known to occur in the vicinity of underground excavations in a region known as the excavation disturbed zone. Such problems are of particular importance for low-permeability, mechanically weak rock such as clays and shales because fractures can be relatively transient as a result of fracture self-sealing processes. Perhaps not as well appreciated is the fact that natural fractures can form in argillaceous rock as a result of hydraulic overpressure caused by phenomena such as disequlibrium compaction, changes in tectonic stress, and mineral dehydration. Overpressure conditions can cause hydraulic fracturing if the fluid pressure leads to tensile effective stresses that exceed the tensile strength of the material. Quantitative modeling of this type of process requires coupling between hydrogeologic processes and geomechanical processes including fracture initiation and propagation. Here we present a computational method for three-dimensional, hydromechanical coupled processes including fracture damage. Fractures are represented as discrete features in a fracture network that interact with a porous rock matrix. Fracture configurations are mapped onto an unstructured, three-dimensonal, Voronoi grid, which is based on a random set of spatial points. Discrete fracture networks (DFN) are represented by the connections of the edges of a Voronoi cells. This methodology has the advantage that fractures can be more easily introduced in response to coupled hydro-mechanical processes and generally eliminates several potential issues associated with the geometry of DFN and numerical gridding. A geomechanical and fracture-damage model is developed here using the Rigid-Body-Spring-Network (RBSN) numerical method. The hydrogelogic and geomechanical models share the same geometrical information from a 3D Voronoi grid and associated nodes, where the scalar field quantities (e.g. temperature, pressure, and saturation) and the generalized displacements are obtained by an integral finite difference method (e.g., TOUGH2) and RBSN, respectively. Fractures propagate along Voronoi cell boundaries as induced stresses evolve and exceed the material strength. Examples of fracture propagation in clay rock are examined for the excavation disturbed zone and for cases in which hydraulic overpressure leads to hydraulic fracture. Fluid flow behavior in these evolving fracture networks and eventual fracture closing and self-sealing are investigated. Funding for this work was provided by the Used Fuel Disposition Campaign, Office of Nuclear Energy, of the U.S. Department of Energy under Contract NumberDE-AC02-05CH11231 with Berkeley Lab.

ATM directs DNA damage responses and proteostasis via genetically separable pathways

PubMed Central

Lee, Ji-Hoon; Mand, Michael R.; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W.; Richards, Alicia L.; Coon, Joshua J.; Paull, Tanya T.

2018-01-01

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes Ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. Here, we genetically separated DNA damage activation of ATM from oxidative activation using separation-of-function mutations. We found that deficiency in ATM activation by Mre11-Rad50-Nbs1 and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of ATM lacking oxidative activation generates widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicates ATM in the control of protein homeostasis. PMID:29317520

Two-stage damage diagnosis based on the distance between ARMA models and pre-whitening filters

NASA Astrophysics Data System (ADS)

Zheng, H.; Mita, A.

2007-10-01

This paper presents a two-stage damage diagnosis strategy for damage detection and localization. Auto-regressive moving-average (ARMA) models are fitted to time series of vibration signals recorded by sensors. In the first stage, a novel damage indicator, which is defined as the distance between ARMA models, is applied to damage detection. This stage can determine the existence of damage in the structure. Such an algorithm uses output only and does not require operator intervention. Therefore it can be embedded in the sensor board of a monitoring network. In the second stage, a pre-whitening filter is used to minimize the cross-correlation of multiple excitations. With this technique, the damage indicator can further identify the damage location and severity when the damage has been detected in the first stage. The proposed methodology is tested using simulation and experimental data. The analysis results clearly illustrate the feasibility of the proposed two-stage damage diagnosis methodology.

An effective means for damage detection of bridges using the contact-point response of a moving test vehicle

NASA Astrophysics Data System (ADS)

Zhang, Bin; Qian, Yao; Wu, Yuntian; Yang, Y. B.

2018-04-01

To further the technique of indirect measurement, the contact-point response of a moving test vehicle is adopted for the damage detection of bridges. First, the contact-point response of the vehicle moving over the bridge is derived both analytically and in central difference form (for field use). Then, the instantaneous amplitude squared (IAS) of the driving component of the contact-point response is calculated by the Hilbert transform, making use of its narrow-band feature. The IAS peaks serve as the key parameter for damage detection. In the numerical simulation, a damage (crack) is modeled by a hinge-spring unit. The feasibility of the proposed method to detect the location and severity of a damage or multi damages of the bridge is verified. Also, the effects of surface roughness, vehicle speed, measurement noise and random traffic are studied. In the presence of ongoing traffic, the damages of the bridge are identified from the repeated or invariant IAS peaks generated for different traffic flows by the same test vehicle over the bridge.

Whole exome sequencing implicates eye development, the unfolded protein response and plasma membrane homeostasis in primary open-angle glaucoma

PubMed Central

Souzeau, Emmanuelle; Sharma, Shiwani; Landers, John; Mills, Richard; Goldberg, Ivan; Healey, Paul R.; Graham, Stuart; Hewitt, Alex W.; Mackey, David A.; Galanopoulos, Anna; Casson, Robert J.; Ruddle, Jonathan B.; Ellis, Jonathan; Leo, Paul; Brown, Matthew A.; MacGregor, Stuart; Lynn, David J.; Burdon, Kathryn P.; Craig, Jamie E.

2017-01-01

Purpose To identify biological processes associated with POAG and its subtypes, high-tension (HTG) and normal-tension glaucoma (NTG), by analyzing rare potentially damaging genetic variants. Methods A total of 122 and 65 unrelated HTG and NTG participants, respectively, with early onset advanced POAG, 103 non-glaucoma controls and 993 unscreened ethnicity-matched controls were included in this study. Study participants without myocilin disease-causing variants and non-glaucoma controls were subjected to whole exome sequencing on an Illumina HiSeq2000. Exomes of participants were sequenced on an Illumina HiSeq2000. Qualifying variants were rare in the general population (MAF < 0.001) and potentially functionally damaging (nonsense, frameshift, splice or predicted pathogenic using SIFT or Polyphen2 software). Genes showing enrichment of qualifying variants in cases were selected for pathway and network analysis using InnateDB. Results POAG cases showed enrichment of rare variants in camera-type eye development genes (p = 1.40×10–7, corrected p = 3.28×10–4). Implicated eye development genes were related to neuronal or retinal development. HTG cases were significantly enriched for key regulators in the unfolded protein response (UPR) (p = 7.72×10–5, corrected p = 0.013). The UPR is known to be involved in myocilin-related glaucoma; our results suggest the UPR has a role in non-myocilin causes of HTG. NTG cases showed enrichment in ion channel transport processes (p = 1.05×10–4, corrected p = 0.027) including calcium, chloride and phospholipid transporters involved in plasma membrane homeostasis. Network analysis also revealed enrichment of the MHC Class I antigen presentation pathway in HTG, and the EGFR1 and cell-cycle pathways in both HTG and NTG. Conclusion This study suggests that mutations in eye development genes are enriched in POAG. HTG can result from aberrant responses to protein misfolding which may be amenable to molecular chaperone therapy. NTG is associated with impaired plasma membrane homeostasis increasing susceptibility to apoptosis. PMID:28264060

In situ analysis of DNA damage response and repair using laser microirradiation.

PubMed

Kim, Jong-Soo; Heale, Jason T; Zeng, Weihua; Kong, Xiangduo; Krasieva, Tatiana B; Ball, Alexander R; Yokomori, Kyoko

2007-01-01

A proper response to DNA damage is critical for the maintenance of genome integrity. However, it is difficult to study the in vivo kinetics and factor requirements of the damage recognition process in mammalian cells. In order to address how the cell reacts to DNA damage, we utilized a second harmonic (532 nm) pulsed Nd:YAG laser to induce highly concentrated damage in a small area in interphase cell nuclei and cytologically analyzed both protein recruitment and modification. Our results revealed for the first time the sequential recruitment of factors involved in two major DNA double-strand break (DSB) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR), and the cell cycle-specific recruitment of the sister chromatid cohesion complex cohesin to the damage site. In this chapter, the strategy developed to study the DNA damage response using the 532-nm Nd:YAG laser will be summarized.

Dynamic extrafloral nectar production: the timing of leaf damage affects the defensive response in Senna mexicana var. chapmanii (Fabaceae).

PubMed

Jones, Ian M; Koptur, Suzanne

2015-01-01

• Extrafloral nectar (EFN) mediates food for protection mutualisms between plants and defensive insects. Understanding sources of variation in EFN production is important because such variations may affect the number and identity of visitors and the effectiveness of plant defense. We investigated the influence of plant developmental stage, time of day, leaf age, and leaf damage on EFN production in Senna mexicana var. chapmanii. The observed patterns of variation in EFN production were compared with those predicted by optimal defense theory.• Greenhouse experiments with potted plants were conducted to determine how plant age, time of day, and leaf damage affected EFN production. A subsequent field study was conducted to determine how leaf damage, and the resulting increase in EFN production, affected ant visitation in S. chapmanii.• More nectar was produced at night and by older plants. Leaf damage resulted in increased EFN production, and the magnitude of the response was greater in plants damaged in the morning than those damaged at night. Damage to young leaves elicited a stronger defensive response than damage to older leaves, in line with optimal defense theory. Damage to the leaves of S. chapmanii also resulted in significantly higher ant visitation in the field.• Extrafloral nectar is an inducible defense in S. chapmanii. Developmental variations in its production support the growth differentiation balance hypothesis, while within-plant variations and damage responses support optimal defense theory. © 2015 Botanical Society of America, Inc.

Bullet trajectory predicts the need for damage control: an artificial neural network model.

PubMed

Hirshberg, Asher; Wall, Matthew J; Mattox, Kenneth L

2002-05-01

Effective use of damage control in trauma hinges on an early decision to use it. Bullet trajectory has never been studied as a marker for damage control. We hypothesize that this decision can be predicted by an artificial neural network (ANN) model based on the bullet trajectory and the patient's blood pressure. A multilayer perceptron ANN predictive model was developed from a data set of 312 patients with single abdominal gunshot injuries. Input variables were the bullet path, trajectory patterns, and admission systolic pressure. The output variable was either a damage control laparotomy or intraoperative death. The best performing ANN was implemented on prospectively collected data from 34 patients. The model achieved a correct classification rate of 0.96 and area under the receiver operating characteristic curve of 0.94. External validation showed the model to have a sensitivity of 88% and specificity of 96%. Model implementation on the prospectively collected data had a correct classification rate of 0.91. Sensitivity analysis showed that systolic pressure, bullet path across the midline, and trajectory involving the right upper quadrant were the three most important input variables. Bullet trajectory is an important, hitherto unrecognized, factor that should be incorporated into the decision to use damage control.

Modeling cognitive deficits following neurodegenerative diseases and traumatic brain injuries with deep convolutional neural networks.

PubMed

Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan

2018-06-01

The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.

An addressable conducting network for autonomic structural health management of composite structures

NASA Astrophysics Data System (ADS)

Takahashi, Kosuke; Park, Jong Se; Hahn, H. Thomas

2010-10-01

The electrical resistance change method (ERCM) has long been an area of interest as an in-service health monitoring system. To apply the ERCM to existing structures, a new concept, the addressable conducting network (ACN), is proposed for autonomic structural health management of graphite/polymer composites. The ACN consists of two sets of conducting lines normal to each other, where one set resides on the top surface of the laminate and the other on the bottom surface. Damage can be detected by monitoring the resistance change 'through the laminate thickness' between two lines. By using a thermally mendable polymer as the matrix, the same conducting lines can be used to supply the electric current needed for resistive heating, thereby allowing the detected damage to be healed. As shown experimentally, the electrical resistance change method using an ACN distinguishes between laminates made of properly and improperly cured prepreg as well as revealing damage generated during three-point bending tests. Finite element analysis was performed to examine the feasibility of the ACN and indicated that the damage can be easily located from the spatial distribution of resistance changes and that the damaged area can be locally heated by supplying a large amount of current to selected conducting lines.

Impact damage monitoring in CFRP using fiber Bragg grating ultrasound sensors

NASA Astrophysics Data System (ADS)

Tsuda, Hiroshi; Lee, Jung-Ryul; Eguchi, Shunji

2006-03-01

Impact damage in CFRP was monitored by ultrasonic inspection method using small-diameter fiber Bragg grating (FBG) sensors. The FBG ultrasound detection system consisted of broadband light source, FBG sensor and tunable optical filter. Broadband light was launched into the FBG sensor. Light reflected from the FBG sensor was transmitted through the tunable optical filter whose transmissive wavelength range is comparable to the reflected wavelength range of the FBG sensor. The operating wavelength of tunable filter was set to optimize the sensitivity of ultrasound detection. Ultrasound vibration was converted into change in intensity of light transmitted through the filter. A cross-ply carbon fiber-reinforced plastic (CFRP) plate was used as a test specimen for impact damage monitoring. A 6.3 X 9mm2 impact damage was introduced by ball dropping. Both FBG ultrasound sensor and piezoelectric ultrasound transmitter were attached on the CFRP surface. The change in responses to ultrasound excited by either spike signal or toneburst signal before and after impact damage was investigated. In response to ultrasound excited by spike signal, the response after impact damage showed a scattered behavior where the period of response signal got longer. In response to ultrasound excited by toneburst signal, damage signal features scattered and distorted waveform. Experimental results proved that the FBG inspection system could monitor a 6.3 X 9mm2 impact damage in CFRP.

The Researches on Damage Detection Method for Truss Structures

NASA Astrophysics Data System (ADS)

Wang, Meng Hong; Cao, Xiao Nan

2018-06-01

This paper presents an effective method to detect damage in truss structures. Numerical simulation and experimental analysis were carried out on a damaged truss structure under instantaneous excitation. The ideal excitation point and appropriate hammering method were determined to extract time domain signals under two working conditions. The frequency response function and principal component analysis were used for data processing, and the angle between the frequency response function vectors was selected as a damage index to ascertain the location of a damaged bar in the truss structure. In the numerical simulation, the time domain signal of all nodes was extracted to determine the location of the damaged bar. In the experimental analysis, the time domain signal of a portion of the nodes was extracted on the basis of an optimal sensor placement method based on the node strain energy coefficient. The results of the numerical simulation and experimental analysis showed that the damage detection method based on the frequency response function and principal component analysis could locate the damaged bar accurately.

Multiscale modelling of Flow-Induced Blood Cell Damage

NASA Astrophysics Data System (ADS)

Liu, Yaling; Sohrabi, Salman

2017-11-01

We study red blood cell (RBC) damage and hemolysis at cellular level. Under high shear rates, pores form on RBC membranes through which hemoglobin (Hb) leaks out and increases free Hb content of plasma leading to hemolysis. By coupling lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single RBC under various shear rates. The developed cellular damage model can be used as a predictive tool for hydrodynamic and hematologic design optimization of blood-wetting medical devices.

Functional vs. Structural Modularity: do they imply each other?

NASA Astrophysics Data System (ADS)

Toroczkai, Zoltan

2009-03-01

While many deterministic and stochastic processes have been proposed to produce heterogeneous graphs mimicking real-world networks, only a handful of studies attempt to connect structure and dynamics with the function(s) performed by the network. In this talk I will present an approach built on the premise that structure, dynamics, and their observed heterogeneity, are implementations of various functions and their compositions. After a brief review of real-world networks where this connection can explicitly be made, I will focus on biological networks. Biological networks are known to possess functionally specialized modules, which perform tasks almost independently of each other. While proposals have been made for the evolutionary emergence of modularity, it is far from clear that adaptation on evolutionary timescales is the sole mechanism leading to functional specialization. We show that non-evolutionary learning can also lead to the formation of functionally specialized modules in a system exposed to multiple environmental constraints. A natural example suggesting that this is possible is the cerebral cortex, where there are clearly delineated functional areas in spite of the largely uniform anatomical construction of the cortical tissue. However, as numerous experiments show, when damaged, regions specialized for a certain function can be retrained to perform functions normally attributed to other regions. We use the paradigm of neural networks to represent a multitasking system, and use several non-evolutionary learning algorithms as mechanisms for phenotypic adaptation. We show that for a network learning to perform multiple tasks, the degree of independence between the tasks dictates the degree of functional specialization emerging in the network. To uncover the functional modules, we introduce a method of node knockouts that explicitly rates the contribution of each node to different tasks (differential robustness). Through a concrete example we also demonstrate the potential inability of purely topology-based clustering methods to detect functional modules. The robustness of these results suggests that similar mechanisms might be responsible for the emergence of functional specialization in other multitasking networks, as well, including social networks.

Comparative proteomic analysis of proteins expression changes in the mammary tissue of cows infected with Escherichia coli mastitis.

PubMed

Zhao, Xiao-wei; Yang, Yong-xin; Huang, Dong-wei; Cheng, Guang-long; Zhao, Hui-ling

2015-01-01

Cows infected with Escherichia (E.) coli usually experience severe clinical symptoms, including damage to mammary tissues, reduced milk yield, and altered milk composition. In order to investigate the host response to E. coli infection and discover novel markers for mastitis treatment, mammary tissue samples were collected from healthy cows and bovines with naturally occurring severe E. coli mastitis. Changes of mammary tissue proteins were examined using two-dimensional gel electrophoresis and label-free proteomic approaches. A total of 95 differentially expressed proteins were identified. Of these, 56 proteins were categorized according to molecular function, cellular component, and biological processes. The most frequent biological processes influenced by the proteins were response to stress, transport, and establishment of localization. Furthermore, a network analysis of the proteins with altered expression in mammary tissues demonstrated that these factors are predominantly involved with binding and structural molecule activities. Vimentin and a-enolase were central "functional hubs" in the network. Based on results from the present study, disease-induced alterations of protein expression in mammary glands and potential markers for the effective treatment of E. coli mastitis were identified. These data have also helped elucidate defense mechanisms that protect the mammary glands and promote the pathogenesis of E. coli mastitis.

Comparative proteomic analysis of proteins expression changes in the mammary tissue of cows infected with Escherichia coli mastitis

PubMed Central

Zhao, Xiao-wei; Huang, Dong-wei; Cheng, Guang-long; Zhao, Hui-ling

2015-01-01

Cows infected with Escherichia (E.) coli usually experience severe clinical symptoms, including damage to mammary tissues, reduced milk yield, and altered milk composition. In order to investigate the host response to E. coli infection and discover novel markers for mastitis treatment, mammary tissue samples were collected from healthy cows and bovines with naturally occurring severe E. coli mastitis. Changes of mammary tissue proteins were examined using two-dimensional gel electrophoresis and label-free proteomic approaches. A total of 95 differentially expressed proteins were identified. Of these, 56 proteins were categorized according to molecular function, cellular component, and biological processes. The most frequent biological processes influenced by the proteins were response to stress, transport, and establishment of localization. Furthermore, a network analysis of the proteins with altered expression in mammary tissues demonstrated that these factors are predominantly involved with binding and structural molecule activities. Vimentin and α-enolase were central "functional hubs" in the network. Based on results from the present study, disease-induced alterations of protein expression in mammary glands and potential markers for the effective treatment of E. coli mastitis were identified. These data have also helped elucidate defense mechanisms that protect the mammary glands and promote the pathogenesis of E. coli mastitis. PMID:25549220

Prediction of strain values in reinforcements and concrete of a RC frame using neural networks

NASA Astrophysics Data System (ADS)

Vafaei, Mohammadreza; Alih, Sophia C.; Shad, Hossein; Falah, Ali; Halim, Nur Hajarul Falahi Abdul

2018-03-01

The level of strain in structural elements is an important indicator for the presence of damage and its intensity. Considering this fact, often structural health monitoring systems employ strain gauges to measure strains in critical elements. However, because of their sensitivity to the magnetic fields, inadequate long-term durability especially in harsh environments, difficulties in installation on existing structures, and maintenance cost, installation of strain gauges is not always possible for all structural components. Therefore, a reliable method that can accurately estimate strain values in critical structural elements is necessary for damage identification. In this study, a full-scale test was conducted on a planar RC frame to investigate the capability of neural networks for predicting the strain values. Two neural networks each of which having a single hidden layer was trained to relate the measured rotations and vertical displacements of the frame to the strain values measured at different locations of the frame. Results of trained neural networks indicated that they accurately estimated the strain values both in reinforcements and concrete. In addition, the trained neural networks were capable of predicting strains for the unseen input data set.

Radionuclide Gas Transport through Nuclear Explosion-Generated Fracture Networks

PubMed Central

Jordan, Amy B.; Stauffer, Philip H.; Knight, Earl E.; Rougier, Esteban; Anderson, Dale N.

2015-01-01

Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. Seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable. PMID:26676058

Radionuclide Gas Transport through Nuclear Explosion-Generated Fracture Networks.

PubMed

Jordan, Amy B; Stauffer, Philip H; Knight, Earl E; Rougier, Esteban; Anderson, Dale N

2015-12-17

Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. Seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable.

Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

PubMed

Yannoutsos, Alexandra; Levy, Bernard I; Safar, Michel E; Slama, Gerard; Blacher, Jacques

2014-02-01

Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

Investigation on the use of artificial neural networks to overcome the effects of environmental and operational changes on guided waves monitoring

NASA Astrophysics Data System (ADS)

El Mountassir, M.; Yaacoubi, S.; Dahmene, F.

2015-07-01

Intelligent feature extraction and advanced signal processing techniques are necessary for a better interpretation of ultrasonic guided waves signals either in structural health monitoring (SHM) or in nondestructive testing (NDT). Such signals are characterized by at least multi-modal and dispersive components. In addition, in SHM, these signals are closely vulnerable to environmental and operational conditions (EOCs), and can be severely affected. In this paper we investigate the use of Artificial Neural Network (ANN) to overcome these effects and to provide a reliable damage detection method with a minimal of false indications. An experimental case of study (full scale pipe) is presented. Damages sizes have been increased and their shapes modified in different steps. Various parameters such as the number of inputs and the number of hidden neurons were studied to find the optimal configuration of the neural network.

Multiscale Modeling of Dewetting Damage in Highly Filled Particulate Composites

NASA Astrophysics Data System (ADS)

Geubelle, P. H.; Inglis, H. M.; Kramer, J. D.; Patel, J. J.; Kumar, N. C.; Tan, H.

2008-02-01

Particle debonding or dewetting constitutes one of the key damage processes in highly filled particulate composites such as solid propellant and other energetic materials. To analyze this failure process, we have developed a multiscale finite element framework that combines, at the microscale, a nonlinear description of the binder response with a cohesive model of the damage process taking place in a representative periodic unit cell (PUC). To relate micro-scale damage to the macroscopic constitutive response of the material, we employ the mathematical theory of homogenization (MTH). After a description of the numerical scheme, we present the results of the damage response of a highly filled particulate composite subjected to a uniaxial macroscopic strain, and show the direct correlation between the complex damage processes taking place in the PUC and the nonlinear macroscopic constitutive response. We also present a detailed study of the PUC size and a comparison between the finite element MTH-based study and a micromechanics model of the dewetting process.

A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection.

PubMed

Ignatieva, Elena V; Igoshin, Alexander V; Yudin, Nikolay S

2017-12-28

Tick-borne encephalitis is caused by the neurotropic, positive-sense RNA virus, tick-borne encephalitis virus (TBEV). TBEV infection can lead to a variety of clinical manifestations ranging from slight fever to severe neurological illness. Very little is known about genetic factors predisposing to severe forms of disease caused by TBEV. The aims of the study were to compile a catalog of human genes involved in response to TBEV infection and to rank genes from the catalog based on the number of neighbors in the network of pairwise interactions involving these genes and TBEV RNA or proteins. Based on manual review and curation of scientific publications a catalog comprising 140 human genes involved in response to TBEV infection was developed. To provide access to data on all genes, the TBEVhostDB web resource ( http://icg.nsc.ru/TBEVHostDB/ ) was created. We reconstructed a network formed by pairwise interactions between TBEV virion itself, viral RNA and viral proteins and 140 genes/proteins from TBEVHostDB. Genes were ranked according to the number of interactions in the network. Two genes/proteins (CCR5 and IFNAR1) that had maximal number of interactions were revealed. It was found that the subnetworks formed by CCR5 and IFNAR1 and their neighbors were a fragments of two key pathways functioning during the course of tick-borne encephalitis: (1) the attenuation of interferon-I signaling pathway by the TBEV NS5 protein that targeted peptidase D; (2) proinflammation and tissue damage pathway triggered by chemokine receptor CCR5 interacting with CD4, CCL3, CCL4, CCL2. Among nine genes associated with severe forms of TBEV infection, three genes/proteins (CCR5, IL10, ARID1B) were found to have protein-protein interactions within the network, and two genes/proteins (IFNL3 and the IL10, that was just mentioned) were up- or down-regulated in response to TBEV infection. Based on this finding, potential mechanisms for participation of CCR5, IL10, ARID1B, and IFNL3 in the host response to TBEV infection were suggested. A database comprising 140 human genes involved in response to TBEV infection was compiled and the TBEVHostDB web resource, providing access to all genes was created. This is the first effort of integrating and unifying data on genetic factors that may predispose to severe forms of diseases caused by TBEV. The TBEVHostDB could potentially be used for assessment of risk factors for severe forms of tick-borne encephalitis and for the design of personalized pharmacological strategies for the treatment of TBEV infection.

RING finger and WD repeat domain 3 (RFWD3) associates with replication protein A (RPA) and facilitates RPA-mediated DNA damage response.

PubMed

Liu, Shangfeng; Chu, Jessica; Yucer, Nur; Leng, Mei; Wang, Shih-Ya; Chen, Benjamin P C; Hittelman, Walter N; Wang, Yi

2011-06-24

DNA damage response is crucial for maintaining genomic integrity and preventing cancer by coordinating the activation of checkpoints and the repair of damaged DNA. Central to DNA damage response are the two checkpoint kinases ATM and ATR that phosphorylate a wide range of substrates. RING finger and WD repeat domain 3 (RFWD3) was initially identified as a substrate of ATM/ATR from a proteomic screen. Subsequent studies showed that RFWD3 is an E3 ubiquitin ligase that ubiquitinates p53 in vitro and positively regulates p53 levels in response to DNA damage. We report here that RFWD3 associates with replication protein A (RPA), a single-stranded DNA-binding protein that plays essential roles in DNA replication, recombination, and repair. Binding of RPA to single-stranded DNA (ssDNA), which is generated by DNA damage and repair, is essential for the recruitment of DNA repair factors to damaged sites and the activation of checkpoint signaling. We show that RFWD3 is physically associated with RPA and rapidly localizes to sites of DNA damage in a RPA-dependent manner. In vitro experiments suggest that the C terminus of RFWD3, which encompass the coiled-coil domain and the WD40 domain, is necessary for binding to RPA. Furthermore, DNA damage-induced phosphorylation of RPA and RFWD3 is dependent upon each other. Consequently, loss of RFWD3 results in the persistent foci of DNA damage marker γH2AX and the repair protein Rad51 in damaged cells. These findings suggest that RFWD3 is recruited to sites of DNA damage and facilitates RPA-mediated DNA damage signaling and repair.

Network measures predict neuropsychological outcome after brain injury

PubMed Central

Warren, David E.; Power, Jonathan D.; Bruss, Joel; Denburg, Natalie L.; Waldron, Eric J.; Sun, Haoxin; Petersen, Steven E.; Tranel, Daniel

2014-01-01

Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as “cortical hubs” of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six “target” hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two “control” hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury. PMID:25225403

External modulation of the sustained attention network in traumatic brain injury.

PubMed

Richard, Nadine M; O'Connor, Charlene; Dey, Ayan; Robertson, Ian H; Levine, Brian

2018-05-07

Traumatic brain injury (TBI) is associated with impairments in processing speed as well as higher-level cognitive functions that depend on distributed neural networks, such as regulating and sustaining attention. Although exogenous alerting cues have been shown to support patients in sustaining attentive, goal-directed behavior, the neural correlates of this rehabilitative effect are unclear. The purpose of this study was to explore the effects of moderate to severe TBI on activity and functional connectivity in the well-documented right-lateralized frontal-subcortical-parietal sustained attention network, and to assess the effects of alerting cues. Using multivariate analysis of fMRI data, TBI patients and matched neurologically healthy (NH) comparison participants were scanned as they performed the Sustained Attention to Response Task (SART) in 60-s blocks, with or without exogenous cueing through brief auditory alerting tones. Results documented inefficient voluntary control of attention in the TBI patients, with reduced functional connectivity in the sustained attention network relative to NH participants. When alerting cues were present during the SART, however, functional connectivity increased and became comparable to activity patterns seen in the NH group. These findings provide novel evidence of a neural mechanism for the facilitatory effects of alerting cues on goal-directed behavior in patients with damaged attentional brain systems, and support their use in cognitive rehabilitation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Amygdala Response to Emotional Stimuli without Awareness: Facts and Interpretations

PubMed Central

Diano, Matteo; Celeghin, Alessia; Bagnis, Arianna; Tamietto, Marco

2017-01-01

Over the past two decades, evidence has accumulated that the human amygdala exerts some of its functions also when the observer is not aware of the content, or even presence, of the triggering emotional stimulus. Nevertheless, there is as of yet no consensus on the limits and conditions that affect the extent of amygdala’s response without focused attention or awareness. Here we review past and recent studies on this subject, examining neuroimaging literature on healthy participants as well as brain-damaged patients, and we comment on their strengths and limits. We propose a theoretical distinction between processes involved in attentional unawareness, wherein the stimulus is potentially accessible to enter visual awareness but fails to do so because attention is diverted, and in sensory unawareness, wherein the stimulus fails to enter awareness because its normal processing in the visual cortex is suppressed. We argue this distinction, along with data sampling amygdala responses with high temporal resolution, helps to appreciate the multiplicity of functional and anatomical mechanisms centered on the amygdala and supporting its role in non-conscious emotion processing. Separate, but interacting, networks relay visual information to the amygdala exploiting different computational properties of subcortical and cortical routes, thereby supporting amygdala functions at different stages of emotion processing. This view reconciles some apparent contradictions in the literature, as well as seemingly contrasting proposals, such as the dual stage and the dual route model. We conclude that evidence in favor of the amygdala response without awareness is solid, albeit this response originates from different functional mechanisms and is driven by more complex neural networks than commonly assumed. Acknowledging the complexity of such mechanisms can foster new insights on the varieties of amygdala functions without awareness and their impact on human behavior. PMID:28119645

Positive Feedback Amplifies the Response of Mitochondrial Membrane Potential to Glucose Concentration in Clonal Pancreatic Beta Cells

PubMed Central

GERENCSER, Akos A.; MOOKERJEE, Shona A.; JASTROCH, Martin; BRAND, Martin D.

2016-01-01

Analysis of the cellular mechanisms of metabolic disorders, including type 2 diabetes mellitus, is complicated by the large number of reactions and interactions in metabolic networks. Metabolic control analysis with appropriate modularization is a powerful method for simplifying and analyzing these networks. To analyze control of cellular energy metabolism in adherent cell cultures of the INS-1 832/13 pancreatic β-cell model we adapted our microscopy assay of absolute mitochondrial membrane potential (ΔψM) to a fluorescence microplate reader format, and applied it in conjunction with cell respirometry. In these cells the sensitive response of ΔψM to extracellular glucose concentration drives glucose-stimulated insulin secretion. Using metabolic control analysis we identified the control properties that generate this sensitive response. Force-flux relationships between ΔψM and respiration were used to calculate kinetic responses to ΔψM of processes both upstream (glucose oxidation) and downstream (proton leak and ATP turnover) of ΔψM. The analysis revealed that glucose-evoked ΔψM hyperpolarization is amplified by increased glucose oxidation activity caused by factors downstream of ΔψM. At high glucose, the hyperpolarized ΔψM is stabilized almost completely by the action of glucose oxidation, whereas proton leak also contribute to the homeostatic control of ΔψM at low glucose. These findings suggest a strong positive feedback loop in the regulation of β-cell energetics, and a possible regulatory role of proton leak in the fasting state. Analysis of islet bioenergetics from published cases of type 2 diabetes suggests that disruption of this feedback can explain the damaged bioenergetic response of β-cells to glucose. PMID:27771512

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation.

PubMed

Yang, Feng; Waters, Katrina M; Miller, John H; Gritsenko, Marina A; Zhao, Rui; Du, Xiuxia; Livesay, Eric A; Purvine, Samuel O; Monroe, Matthew E; Wang, Yingchun; Camp, David G; Smith, Richard D; Stenoien, David L

2010-11-30

High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.

Phosphoproteomics Profiling of Human Skin Fibroblast Cells Reveals Pathways and Proteins Affected by Low Doses of Ionizing Radiation

PubMed Central

Yang, Feng; Waters, Katrina M.; Miller, John H.; Gritsenko, Marina A.; Zhao, Rui; Du, Xiuxia; Livesay, Eric A.; Purvine, Samuel O.; Monroe, Matthew E.; Wang, Yingchun; Camp, David G.; Smith, Richard D.; Stenoien, David L.

2010-01-01

Background High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation. Principal Findings We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conclusions Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health. PMID:21152398

Hypothermia modulates the DNA damage response to ionizing radiation in human peripheral blood lymphocytes.

PubMed

Lisowska, Halina; Cheng, Lei; Sollazzo, Alice; Lundholm, Lovisa; Wegierek-Ciuk, Aneta; Sommer, Sylwester; Lankoff, Anna; Wojcik, Andrzej

2018-06-01

Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage. It was suggested to be due to an effective transformation of DNA damage to chromosomal damage at low temperature. The purpose of the study was to analyze the kinetics of aberration formation during the first hours after exposing human peripheral blood lymphocytes to ionizing radiation at 0.8 °C and 37 °C. To this end, we applied the technique of premature chromosome condensation. In addition, DNA damage response was analyzed by measuring the levels of phosphorylated DNA damage responsive proteins ATM, DNA-PK and p53 and mRNA levels of the radiation-responsive genes BBC3, FDXR, GADD45A, XPC, MDM2 and CDKN1A. A consistently lower frequency of chromosomal breaks was observed in cells exposed at 0.8 °C as compared to 37 °C already after 30 minutes postexposure. This effect was accompanied by elevated levels of phosphorylated ATM and DNA-PK proteins and a reduced immediate level of phosphorylated p53 and of the responsive genes. Low temperature at exposure appears to promote DNA repair leading to reduced transformation of DNA damage to chromosomal aberrations.

Approaches for characterizing threshold dose-response relationships for DNA-damage pathways involved in carcinogenicity in vivo and micronuclei formation in vitro.

PubMed

Clewell, Rebecca A; Andersen, Melvin E

2016-05-01

Assessing the shape of dose-response curves for DNA-damage in cellular systems and for the consequences of DNA damage in intact animals remains a controversial topic. This overview looks at aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of cellular DNA-damage/repair and their role in defining the shape of dose-response curves using an in vivo example with formaldehyde and in vitro examples for micronuclei (MN) formation with several test compounds. Formaldehyde is both strongly mutagenic and an endogenous metabolite in cells. With increasing inhaled concentrations, there were transitions in gene changes, from activation of selective stress pathway genes at low concentrations, to activation of pathways for cell-cycle control, p53-DNA damage, and stem cell niche pathways at higher exposures. These gene expression changes were more consistent with dose-dependent transitions in the PD responses to formaldehyde in epithelial cells in the intact rat rather than the low-dose linear extrapolation methods currently used for carcinogens. However, more complete PD explanations of non-linear dose response for creation of fixed damage in cells require detailed examination of cellular responses in vitro using measures of DNA damage and repair that are not easily accessible in the intact animal. In the second section of the article, we illustrate an approach from our laboratory that develops fit-for-purpose, in vitro assays and evaluates the PD of DNA damage and repair through studies using prototypical DNA-damaging agents. Examination of a broad range of responses in these cells showed that transcriptional upregulation of cell cycle control and DNA repair pathways only occurred at doses higher than those causing overt damage fixed damage-measured as MN formation. Lower levels of damage appear to be handled by post-translational repair process using pre-existing proteins. In depth evaluation of the PD properties of one such post-translational process (formation of DNA repair centers; DRCs) has indicated that the formation of DRCs and their ability to complete repair before replication are consistent with threshold behaviours for mutagenesis and, by extension, with chemical carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation

PubMed Central

Xie, Da-Fei; Xie, Yi; Liu, Xiao-Dan; Wang, Qi; Sui, Li; Song, Man; Zhang, Hong; Zhou, Jianhua; Zhou, Ping-Kun

2016-01-01

Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET) value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, we analyzed the proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from different LET values of heavy ion 12C. Total proteins were extracted from these cells and examined by Q Exactive with Liquid Chromatography (LC)—Electrospray Ionization (ESI) Tandem MS (MS/MS). Using bioinformatics approaches, differentially expressed proteins with 1.5 or 2.0-fold changes between different dosages of exposure were compared. With the higher the dosage and/or LET of ion irradiation, the worse response the cells were in terms of protein expression. For instance, compared to the control (0 Gy), 771 (20.2%) proteins in cells irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/μm, 313 proteins (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/μm, and 243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/μm exhibited changes of 1.5-fold or greater. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Munich Information Center for Protein Sequences (MIPS) analysis, and BioCarta analysis all indicated that RNA metabolic processes (RNA splicing, destabilization and deadenylation) and proteasome pathways may play key roles in the cellular response to heavy-ion irradiation. Proteasome pathways ranked highest among all biological processes associated with heavy carbon-ion irradiation. In addition, network analysis revealed that cellular pathways involving proteins such as Col1a1 and Fn1 continued to respond to high dosages of heavy-ion irradiation, suggesting that these pathways still protect cells against damage. However, pathways such as those involving Ikbkg1 responded better at lower dosages than at higher dosages, implying that cell damage would occur when the networks involving these proteins stop responding. Our investigation provides valuable proteomic information for elucidating the mechanism of biological effects induced by carbon ions in general. PMID:27711237

Axonal/Glial Upregulation of EphB/ephrin-B Signaling in Mouse Experimental Ocular Hypertension

PubMed Central

Tran, Tony; Sretavan, David

2010-01-01

Purpose. To use a laser-induced ocular hypertension (LIOH) mouse model to examine the optic nerve head (ONH) expression of EphB/ephrin-B, previously shown to be upregulated in glaucomatous DBA/2J mice. To relate ephrin-B reverse signaling with states of axonal response to disease. Methods. LIOH was induced unilaterally in CD-1 mice by laser photocoagulation of limbal and episcleral veins. Intraocular pressure (IOP) was measured with a tonometer. EphB/ephrin-B mRNA expression was assessed by in situ hybridization on eyecup cryosections and real-time PCR. Cell specific markers were used to identify the cellular origin of EphB/ephrin-B expression. Activation of ephrin-B signaling was investigated with a phosphospecific antibody on cryosections and retinal whole-mounts. Results. Upregulation of EphB/ephrin-B expression occurred early within a day of IOP elevation. A transient increase of phosphorylation-dependent ephrin-B (pEB) reverse signaling was observed in ONH axons, microglia, and some astrocytes. Morphologically unaffected retinal ganglion cell (RGC) axons differed from axons with reactive aberrant trajectories by exhibiting increased pEB activation, whereas pEB levels in morphologically affected axons were comparable to those of controls. Conclusions. An Eph-ephrin signaling network is activated at the ONH after LIOH in CD-1 mice, either before or coincident with the initial morphologic signs of RGC axon damage reported previously. Of note, ephrin-B reverse signaling was transiently upregulated in RGC axons at the ONH early in their response to IOP elevation but was downregulated in axons that had been damaged by glaucomatous injury and exhibited aberrant trajectories. Ephrin-B reverse signaling may mark RGC axons for damage or confer a protective advantage against injury. PMID:19815726

Study of cumulative fatigue damage detection for used parts with nonlinear output frequency response functions based on NARMAX modelling

NASA Astrophysics Data System (ADS)

Huang, Honglan; Mao, Hanying; Mao, Hanling; Zheng, Weixue; Huang, Zhenfeng; Li, Xinxin; Wang, Xianghong

2017-12-01

Cumulative fatigue damage detection for used parts plays a key role in the process of remanufacturing engineering and is related to the service safety of the remanufactured parts. In light of the nonlinear properties of used parts caused by cumulative fatigue damage, the based nonlinear output frequency response functions detection approach offers a breakthrough to solve this key problem. First, a modified PSO-adaptive lasso algorithm is introduced to improve the accuracy of the NARMAX model under impulse hammer excitation, and then, an effective new algorithm is derived to estimate the nonlinear output frequency response functions under rectangular pulse excitation, and a based nonlinear output frequency response functions index is introduced to detect the cumulative fatigue damage in used parts. Then, a novel damage detection approach that integrates the NARMAX model and the rectangular pulse is proposed for nonlinear output frequency response functions identification and cumulative fatigue damage detection of used parts. Finally, experimental studies of fatigued plate specimens and used connecting rod parts are conducted to verify the validity of the novel approach. The obtained results reveal that the new approach can detect cumulative fatigue damages of used parts effectively and efficiently and that the various values of the based nonlinear output frequency response functions index can be used to detect the different fatigue damages or working time. Since the proposed new approach can extract nonlinear properties of systems by only a single excitation of the inspected system, it shows great promise for use in remanufacturing engineering applications.

Intelligent seismic risk mitigation system on structure building

NASA Astrophysics Data System (ADS)

Suryanita, R.; Maizir, H.; Yuniorto, E.; Jingga, H.

2018-01-01

Indonesia located on the Pacific Ring of Fire, is one of the highest-risk seismic zone in the world. The strong ground motion might cause catastrophic collapse of the building which leads to casualties and property damages. Therefore, it is imperative to properly design the structural response of building against seismic hazard. Seismic-resistant building design process requires structural analysis to be performed to obtain the necessary building responses. However, the structural analysis could be very difficult and time consuming. This study aims to predict the structural response includes displacement, velocity, and acceleration of multi-storey building with the fixed floor plan using Artificial Neural Network (ANN) method based on the 2010 Indonesian seismic hazard map. By varying the building height, soil condition, and seismic location in 47 cities in Indonesia, 6345 data sets were obtained and fed into the ANN model for the learning process. The trained ANN can predict the displacement, velocity, and acceleration responses with up to 96% of predicted rate. The trained ANN architecture and weight factors were later used to build a simple tool in Visual Basic program which possesses the features for prediction of structural response as mentioned previously.

RNF168 forms a functional complex with RAD6 during the DNA damage response

PubMed Central

Liu, Chao; Wang, Degui; Wu, Jiaxue; Keller, Jennifer; Ma, Teng; Yu, Xiaochun

2013-01-01

Summary Protein ubiquitination plays an important role in initiating the DNA damage response. Following DNA damage, E2 ubiquitin conjugating enzymes are crucial for catalyzing substrate ubiquitination that recruits downstream DNA repair factors to DNA lesions. To identify novel E2 conjugating enzymes important for initiating the DNA-damage-induced ubiquitination cascade, we screened most of the known E2 enzymes and found that RAD6A and RAD6B function together with RNF168 in the ionizing radiation (IR)-induced DNA damage response. Similarly to RNF168-deficient cells, RAD6A- or RAD6B-deficient cells exhibit a reduction in DNA-damage-induced protein ubiquitination. Correspondingly, DNA-damage-induced foci formation of DNA damage repair proteins, such as BRCA1 and 53BP1, is impaired in the absence of RAD6A or RAD6B. Moreover, the RNF168–RAD6 complex targeted histone H1.2 for ubiquitination in vitro and regulated DNA-damage-induced histone H1.2 ubiquitination in vivo. Collectively, these data demonstrate that RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade. PMID:23525009

Damage localization of marine risers using time series of vibration signals

NASA Astrophysics Data System (ADS)

Liu, Hao; Yang, Hezhen; Liu, Fushun

2014-10-01

Based on dynamic response signals a damage detection algorithm is developed for marine risers. Damage detection methods based on numerous modal properties have encountered issues in the researches in offshore oil community. For example, significant increase in structure mass due to marine plant/animal growth and changes in modal properties by equipment noise are not the result of damage for riser structures. In an attempt to eliminate the need to determine modal parameters, a data-based method is developed. The implementation of the method requires that vibration data are first standardized to remove the influence of different loading conditions and the autoregressive moving average (ARMA) model is used to fit vibration response signals. In addition, a damage feature factor is introduced based on the autoregressive (AR) parameters. After that, the Euclidean distance between ARMA models is subtracted as a damage indicator for damage detection and localization and a top tensioned riser simulation model with different damage scenarios is analyzed using the proposed method with dynamic acceleration responses of a marine riser as sensor data. Finally, the influence of measured noise is analyzed. According to the damage localization results, the proposed method provides accurate damage locations of risers and is robust to overcome noise effect.

Damage detection in sandwich composite materials using laser vibrometry in conjunction with nonlinear system identification

NASA Astrophysics Data System (ADS)

Underwood, Sara; Koester, David; Adams, Douglas E.

2009-03-01

Fiberglass sandwich panels are tested to study a vibration-based method for locating damage in composite materials. This method does not rely on a direct comparison of the natural frequencies, mode shapes, or residues in the forced vibration response data. Specifically, a nonlinear system identification based method for damage detection is sought that reduces the sensitivity of damage detection results to changes in vibration measurements due to variations in boundary conditions, environmental conditions, and material properties of the panel. Damage mechanisms considered include a disbond between the core and face sheet and a crack within the core. A panel is excited by a skewed piezoelectric actuator over a broad frequency range while a three-dimensional scanning laser vibrometer measures the surface velocity of the panel along three orthogonal axes. The forced frequency response data measured using the scanning laser vibrometer at multiple excitation amplitudes is processed to identify areas of the panel that exhibit significant nonlinear response characteristics. It is demonstrated that these localized nonlinearities in the panel coincide with the damaged areas of the composite material. Because changes in the measured frequency response functions due to nonlinear distortions associated with the damage can be identified without comparing the vibration data to a reference (baseline) signature of the undamaged material, this vibration technique for damage detection in composite materials exhibits less sensitivity to variations in the underlying linear characteristics than traditional methods. It is also demonstrated that the damage at a given location can be classified as either due to a disbond or core crack because these two types of damage produce difference signatures when comparing the multi-amplitude frequency response functions.

Cell Cycle Regulators Guide Mitochondrial Activity in Radiation-Induced Adaptive Response

PubMed Central

Alexandrou, Aris T.

2014-01-01

Abstract Significance: There are accruing concerns on potential genotoxic agents present in the environment including low-dose ionizing radiation (LDIR) that naturally exists on earth's surface and atmosphere and is frequently used in medical diagnosis and nuclear industry. Although its long-term health risk is being evaluated and remains controversial, LDIR is shown to induce temporary but significant adaptive responses in mammalian cells and animals. The mechanisms guiding the mitochondrial function in LDIR-induced adaptive response represent a unique communication between DNA damage and cellular metabolism. Elucidation of the LDIR-regulated mitochondrial activity may reveal new mechanisms adjusting cellular function to cope with hazardous environmental stress. Recent Advances: Key cell cycle regulators, including Cyclin D1/CDK4 and Cyclin B1/cyclin-dependent kinase 1 (CDK1) complexes, are actively involved in the regulation of mitochondrial functions via phosphorylation of their mitochondrial targets. Accumulating new evidence supports a concept that the Cyclin B1/CDK1 complex acts as a mediator in the cross talk between radiation-induced DNA damage and mitochondrial functions to coordinate cellular responses to low-level genotoxic stresses. Critical Issues: The LDIR-mediated mitochondrial activity via Cyclin B1/CDK1 regulation is an irreplaceable network that is able to harmonize vital cellular functions with adjusted mitochondrial metabolism to enhance cellular homeostasis. Future Directions: Further investigation of the coordinative mechanism that regulates mitochondrial activities in sublethal stress conditions, including LDIR, will reveal new insights of how cells cope with genotoxic injury and will be vital for future targeted therapeutic interventions that reduce environmental injury and cancer risk. Antioxid. Redox Signal. 20, 1463–1480. PMID:24180340

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

PubMed

Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

2017-06-18

Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress

PubMed Central

Wilson, Andrew F.; Li, Xue

2017-01-01

ABSTRACT Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G2/M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress. PMID:28475398

Launch Pad 39 Hail Monitor Array System

NASA Technical Reports Server (NTRS)

2008-01-01

Weather conditions at Kennedy Space Center are extremely dynamic, and they greatly affect the safety of the Space Shuttles sitting on the launch pads. For example, on May 13, 1999, the foam on the External Tank (ET) of STS-96 was significantly damaged by hail at the launch pad, requiring rollback to the Vehicle Assembly Building. The loss of ET foam on STS-114 in 2005 intensified interest in monitoring and measuring damage to ET foam, especially from hail. But hail can be difficult to detect and monitor because it is often localized and obscured by heavy rain. Furthermore, the hot Florida climate usually melts the hail even before the rainfall subsides. In response, the hail monitor array (HMA) system, a joint effort of the Applied Physics Laboratory operated by NASA and ASRC Aerospace at KSC, was deployed for operational testing in the fall of 2006. Volunteers from the Community Collaborative Rain, Hail, and Snow (CoCoRaHS) network, in conjunction with Colorado State University, continue to test duplicate hail monitor systems deployed in the high plains of Colorado.