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Sample records for early response mechanisms

  1. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    KAUST Repository

    Yun, Kil-Young; Park, Myoung Ryoul; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Mauleon, Ramil; Wijaya, Edward; Bajic, Vladimir B.; Bruskiewich, Richard; de los Reyes, Benildo G

    2010-01-01

    -plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress

  2. The temporal relationship between reduction of early imitative responses and the development of attention mechanisms

    Directory of Open Access Journals (Sweden)

    Benga Oana

    2003-12-01

    Full Text Available Abstract Background To determine whether early imitative responses fade out following the maturation of attentional mechanisms, the relationship between primitive imitation behaviors and the development of attention was examined in 4-month-old infants. They were divided into high and low imitators, based on an index of imitation. The status of attention was assessed by studying inhibition of return (IOR. Nine-month-old infants were also tested to confirm the hypothesis. Results The IOR latency data replicate previous results that infants get faster to produce a covert shift of attention with increasing age. However, those 4-month-olds who showed less imitation had more rapid saccades to the cue before target presentation. Conclusion The cortical control of saccade planning appears to be related to an apparent drop in early imitation. We interpret the results as suggesting a relationship between the status of imitation and the neural development of attention-related eye movement.

  3. Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum.

    Science.gov (United States)

    Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

    2017-07-26

    The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.

  4. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    Directory of Open Access Journals (Sweden)

    Wijaya Edward

    2010-01-01

    Full Text Available Abstract Background The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10°C, an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach. Results Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10°C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters. Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2 spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters. Conclusion Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries.

  5. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    KAUST Repository

    Yun, Kil-Young

    2010-01-25

    Background: The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10C), an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach.Results: Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters.Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters.Conclusion: Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries. 2010 Yun et al; licensee BioMed Central Ltd.

  6. Target or barrier? The cell wall of early- and later- diverging plants vs cadmium toxicity: differences in the response mechanisms

    Directory of Open Access Journals (Sweden)

    Luigi eParrotta

    2015-03-01

    Full Text Available Increasing industrialization and urbanization result in emission of pollutants in the environment including toxic heavy metals, as cadmium and lead. Among the different heavy metals contaminating the environment, cadmium raises great concern, as it is ecotoxic and as such can heavily impact ecosystems. The cell wall is the first structure of plant cells to come in contact with heavy metals. Its composition, characterized by proteins, polysaccharides and in some instances lignin and other phenolic compounds, confers the ability to bind non-covalently and/or covalently heavy metals via functional groups. A strong body of evidence in the literature has shown the role of the cell wall in heavy metal response: it sequesters heavy metals, but at the same time its synthesis and composition can be severely affected. The present review analyzes the dual property of plant cell walls, i.e. barrier and target of heavy metals, by taking Cd toxicity as example. Following a summary of the known physiological and biochemical responses of plants to Cd, the review compares the wall-related mechanisms in early- and later-diverging land plants, by considering the diversity in cell wall composition. By doing so, common as well as unique response mechanisms to metal/cadmium toxicity are identified among plant phyla and discussed. After discussing the role of hyperaccumulators’ cell walls as a particular case, the review concludes by considering important aspects for plant engineering.

  7. Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response.

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    Maria Jesus Iglesias

    Full Text Available Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS.To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches--gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII, which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF, was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines, was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40% was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at

  8. Mechanical response of composites

    NARCIS (Netherlands)

    Camanho, Pedro P.; Dávila, C.G.; Pinho, Silvestre T.; Remmers, J.J.C.

    2008-01-01

    This book contains twelve selected papers presented at the ECCOMAS Thematic Conference ? Mechanical Response of Composites, and the papers presented by the three plenary speakers. It describes recent advances in the field of analysis models for the mechanical response of advanced composite

  9. Hormonal responses during early embryogenesis in maize.

    Science.gov (United States)

    Chen, Junyi; Lausser, Andreas; Dresselhaus, Thomas

    2014-04-01

    Plant hormones have been shown to regulate key processes during embryogenesis in the model plant Arabidopsis thaliana, but the mechanisms that determine the peculiar embryo pattern formation of monocots are largely unknown. Using the auxin and cytokinin response markers DR5 and TCSv2 (two-component system, cytokinin-responsive promoter version #2), as well as the auxin efflux carrier protein PIN1a (PINFORMED1a), we have studied the hormonal response during early embryogenesis (zygote towards transition stage) in the model and crop plant maize. Compared with the hormonal response in Arabidopsis, we found that detectable hormone activities inside the developing maize embryo appeared much later. Our observations indicate further an important role of auxin, PIN1a and cytokinin in endosperm formation shortly after fertilization. Apparent auxin signals within adaxial endosperm cells and cytokinin responses in the basal endosperm transfer layer as well as chalazal endosperm are characteristic for early seed development in maize. Moreover, auxin signalling in endosperm cells is likely to be involved in exogenous embryo patterning as auxin responses in the endosperm located around the embryo proper correlate with adaxial embryo differentiation and outgrowth. Overall, the comparison between Arabidopsis and maize hormone response and flux suggests intriguing mechanisms in monocots that are used to direct their embryo patterning, which is significantly different from that of eudicots.

  10. Mechanical Response of Thermoelectric Materials

    Energy Technology Data Exchange (ETDEWEB)

    Wereszczak, Andrew A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Case, Eldon D. [Michigan State Univ., East Lansing, MI (United States)

    2015-05-01

    A sufficient mechanical response of thermoelectric materials (TEMats) to structural loadings is a prerequisite to the exploitation of any candidate TEMat's thermoelectric efficiency. If a TEMat is mechanically damaged or cracks from service-induced stresses, then its thermal and electrical functions can be compromised or even cease. Semiconductor TEMats tend to be quite brittle and have a high coefficient of thermal expansion; therefore, they can be quite susceptible to mechanical failure when subjected to operational thermal gradients. Because of this, sufficient mechanical response (vis-a-vis, mechanical properties) of any candidate TEMat must be achieved and sustained in the context of the service-induced stress state to which it is subjected. This report provides an overview of the mechanical responses of state-of-the-art TEMats; discusses the relevant properties that are associated with those responses and their measurement; and describes important, nonequilibrium phenomena that further complicate their use in thermoelectric devices. For reference purposes, the report also includes several appendixes that list published data on elastic properties and strengths of a variety of TEMats.

  11. Neurobiological mechanisms of placebo responses.

    Science.gov (United States)

    Zubieta, Jon-Kar; Stohler, Christian S

    2009-03-01

    Expectations, positive or negative, are modulating factors influencing behavior. They are also thought to underlie placebo effects, potentially impacting perceptions and biological processes. We used sustained pain as a model to determine the neural mechanisms underlying placebo-induced analgesia and affective changes in healthy humans. Subjects were informed that they could receive either an active agent or an inactive compound, similar to routine clinical trials. Using PET and the mu-opioid selective radiotracer [(11)C]carfentanil we demonstrate placebo-induced activation of opioid neurotransmission in a number of brain regions. These include the rostral anterior cingulate, orbitofrontal and dorsolateral prefrontal cortex, anterior and posterior insula, nucleus accumbens, amygdala, thalamus, hypothalamus, and periaqueductal grey. Some of these regions overlap with those involved in pain and affective regulation but also motivated behavior. The activation of endogenous opioid neurotransmission was further associated with reductions in pain report and negative affective state. Additional studies with the radiotracer [(11)C]raclopride, studies labeling dopamine D2/3 receptors, also demonstrate the activation of nucleus accumbens dopamine during placebo administration under expectation of analgesia. Both dopamine and opioid neurotransmission were related to expectations of analgesia and deviations from those initial expectations. When the activity of the nucleus accumbens was probed with fMRI using a monetary reward expectation paradigm, its activation was correlated with both dopamine, opioid responses to placebo in this region and the formation of placebo analgesia. These data confirm that specific neural circuits and neurotransmitter systems respond to the expectation of benefit during placebo administration, inducing measurable physiological changes.

  12. Characterization of early host responses in adults with dengue disease

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    Ling Ling

    2011-08-01

    Full Text Available Abstract Background While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. Methods In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on denguevirus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Results In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut, while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1, CCL8 (MCP-2, CXCL10 (IP-10 and CCL3 (MIP-1α, antimicrobial peptide β-defensin 1 (DEFB1, desmosome/intermediate junction component plakoglobin (JUP and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1. Conclusions These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease.

  13. Orthostatic intolerance and the cardiovascular response to early postoperative mobilization

    DEFF Research Database (Denmark)

    Bundgaard-Nielsen, M; Jørgensen, Christoffer Calov; Jørgensen, T B

    2009-01-01

    BACKGROUND: A key element in enhanced postoperative recovery is early mobilization which, however, may be hindered by orthostatic intolerance, that is, an inability to sit or stand because of symptoms of cerebral hypoperfusion as intolerable dizziness, nausea and vomiting, feeling of heat...... of orthostatic intolerance. In contrast, 8 (50%) and 2 (12%) patients were orthostatic intolerant at 6 and approximately 22 h after surgery, respectively. Before surgery, SAP, DAP, and TPR increased (P0.05) and Scv(O2) decreased (P... the preoperative evaluation (P>0.05). CONCLUSIONS: The early postoperative postural cardiovascular response is impaired after radical prostatectomy with a risk of orthostatic intolerance, limiting early postoperative mobilization. The pathogenic mechanisms include both impaired TPR and CO responses....

  14. Early Screening for Tetrahydrobiopterin Responsiveness in Phenylketonuria.

    Science.gov (United States)

    Porta, Francesco; Spada, Marco; Ponzone, Alberto

    2017-08-01

    Since 2007, synthetic tetrahydrobiopterin (BH4) has been approved as a therapeutic option in BH4-responsive phenylketonuria (PKU) and since 2015 extended to infants younger than 4 years in Europe. The current definition of BH4 responsiveness relies on the observation of a 20% to 30% blood phenylalanine (Phe) decrease after BH4 administration, under nonstandardized conditions. By this definition, however, patients with the same genotype or even the same patients were alternatively reported as responsive or nonresponsive to the cofactor. These inconsistencies are troubling, as frustrating patient expectations and impairing cost-effectiveness of BH4-therapy. Here we tried a quantitative procedure through the comparison of the outcome of a simple Phe and a combined Phe plus BH4 loading in a series of infants with PKU, most of them harboring genotypes already reported as BH4 responsive. Under these ideal conditions, blood Phe clearance did not significantly differ after the 2 types of loading, and a 20% to 30% decrease of blood Phe occurred irrespective of BH4 administration in milder forms of PKU. Such early screening for BH4 responsiveness, based on a quantitative assay, is essential for warranting an evidence-based and cost-effective therapy in those patients with PKU eventually but definitely diagnosed as responsive to the cofactor. Copyright © 2017 by the American Academy of Pediatrics.

  15. T-cell activation and early gene response in dogs.

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    Sally-Anne Mortlock

    Full Text Available T-cells play a crucial role in canine immunoregulation and defence against invading pathogens. Proliferation is fundamental to T-cell differentiation, homeostasis and immune response. Initiation of proliferation following receptor mediated stimuli requires a temporally programmed gene response that can be identified as immediate-early, mid- and late phases. The immediate-early response genes in T-cell activation engage the cell cycle machinery and promote subsequent gene activation events. Genes involved in this immediate-early response in dogs are yet to be identified. The present study was undertaken to characterise the early T-cell gene response in dogs to improve understanding of the genetic mechanisms regulating immune function. Gene expression profiles were characterised using canine gene expression microarrays and quantitative reverse transcription PCR (qRT-PCR, and paired samples from eleven dogs. Significant functional annotation clusters were identified following stimulation with phytohemagluttinin (PHA (5μg/ml, including the Toll-like receptor signaling pathway and phosphorylation pathways. Using strict statistical criteria, 13 individual genes were found to be differentially expressed, nine of which have ontologies that relate to proliferation and cell cycle control. These included, prostaglandin-endoperoxide synthase 2 (PTGS2/COX2, early growth response 1 (EGR1, growth arrest and DNA damage-inducible gene (GADD45B, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, V-FOS FBJ murine osteosarcoma viral oncogene homolog (FOS, early growth response 2 (EGR2, hemogen (HEMGN, polo-like kinase 2 (PLK2 and polo-like kinase 3 (PLK3. Differential gene expression was re-examined using qRT-PCR, which confirmed that EGR1, EGR2, PMAIP1, PTGS2, FOS and GADD45B were significantly upregulated in stimulated cells and ALAS2 downregulated. PTGS2 and EGR1 showed the highest levels of response in these dogs. Both of these genes are involved in

  16. Mechanisms of subliminal response priming.

    Science.gov (United States)

    Kiesel, Andrea; Kunde, Wilfried; Hoffmann, Joachim

    2008-07-15

    Subliminal response priming has been considered to operate on several stages, e.g. perceptual, central or motor stages might be affected. While primes' impact on target perception has been clearly demonstrated, semantic response priming recently has been thrown into doubt (e.g. Klinger, Burton, & Pitts, 2000). Finally, LRP studies have revealed that subliminal primes evoke motor processes. Yet, the premises for such prime-evoked motor activation are not settled. A transfer of priming to stimuli that have never been presented as targets appears particularly interesting because it suggests a level of processing that goes beyond a reactivation of previously acquired S-R links. Yet, such transfer has not always withstood empirical testing. To account for these contradictory results, we proposed a two-process model (Kunde, Kiesel, & Hoffmann, 2003): First, participants build up expectations regarding imperative stimuli for the required responses according to experience and/or instructions. Second, stimuli that match these "action triggers" directly activate the corresponding motor responses irrespective of their conscious identification. In line with these assumptions, recent studies revealed that non-target primes induce priming when they fit the current task intentions and when they are expected in the experimental setting.

  17. Decreased heart rate variability responses during early postoperative mobilization

    DEFF Research Database (Denmark)

    Jans, Øivind; Brinth, Louise; Kehlet, Henrik

    2015-01-01

    in relation to postural change. METHODS: A standardized mobilization protocol before, 6 and 24 h after surgery was performed in 23 patients scheduled for elective THA. Beat-to-beat arterial blood pressure was measured by photoplethysmography and HRV was derived from pulse wave interbeat intervals and analysed......BACKGROUND: Intact orthostatic blood pressure regulation is essential for early mobilization after surgery. However, postoperative orthostatic hypotension and intolerance (OI) may delay early ambulation. The mechanisms of postoperative OI include impaired vasopressor responses relating...... and postural responses in arterial pressures decreased compared to preoperative conditions. During standing HF variation increased by 16.7 (95 % CI 8.0-25.0) normalized units (nu) at 6 h and 10.7 (2.0-19.4) nu at 24 h compared to the preoperative evaluation. At 24 h the LF/HF ratio decreased from 1.8 (1...

  18. Modeling the mechanical response of PBX 9501

    Energy Technology Data Exchange (ETDEWEB)

    Ragaswamy, Partha [Los Alamos National Laboratory; Lewis, Matthew W [Los Alamos National Laboratory; Liu, Cheng [Los Alamos National Laboratory; Thompson, Darla G [Los Alamos National Laboratory

    2010-01-01

    An engineering overview of the mechanical response of Plastic-Bonded eXplosives (PBXs), specifically PBX 9501, will be provided with emphasis on observed mechanisms associated with different types of mechanical testing. Mechanical tests in the form of uniaxial tension, compression, cyclic loading, creep (compression and tension), and Hopkinson bar show strain rate and temperature dependence. A range of mechanical behavior is observed which includes small strain recoverable response in the form of viscoelasticity; change in stiffness and softening beyond peak strength due to damage in the form microcracks, debonding, void formation and the growth of existing voids; inelastic response in the form of irrecoverable strain as shown in cyclic tests, and viscoelastic creep combined with plastic response as demonstrated in creep and recovery tests. The main focus of this paper is to elucidate the challenges and issues involved in modeling the mechanical behavior of PBXs for simulating thermo-mechanical responses in engineering components. Examples of validation of a constitutive material model based on a few of the observed mechanisms will be demonstrated against three point bending, split Hopkinson pressure bar and Brazilian disk geometry.

  19. Early years of Computational Statistical Mechanics

    Science.gov (United States)

    Mareschal, Michel

    2018-05-01

    Evidence that a model of hard spheres exhibits a first-order solid-fluid phase transition was provided in the late fifties by two new numerical techniques known as Monte Carlo and Molecular Dynamics. This result can be considered as the starting point of computational statistical mechanics: at the time, it was a confirmation of a counter-intuitive (and controversial) theoretical prediction by J. Kirkwood. It necessitated an intensive collaboration between the Los Alamos team, with Bill Wood developing the Monte Carlo approach, and the Livermore group, where Berni Alder was inventing Molecular Dynamics. This article tells how it happened.

  20. Stomatal Blue Light Response Is Present in Early Vascular Plants.

    Science.gov (United States)

    Doi, Michio; Kitagawa, Yuki; Shimazaki, Ken-ichiro

    2015-10-01

    Light is a major environmental factor required for stomatal opening. Blue light (BL) induces stomatal opening in higher plants as a signal under the photosynthetic active radiation. The stomatal BL response is not present in the fern species of Polypodiopsida. The acquisition of a stomatal BL response might provide competitive advantages in both the uptake of CO2 and prevention of water loss with the ability to rapidly open and close stomata. We surveyed the stomatal opening in response to strong red light (RL) and weak BL under the RL with gas exchange technique in a diverse selection of plant species from euphyllophytes, including spermatophytes and monilophytes, to lycophytes. We showed the presence of RL-induced stomatal opening in most of these species and found that the BL responses operated in all euphyllophytes except Polypodiopsida. We also confirmed that the stomatal opening in lycophytes, the early vascular plants, is driven by plasma membrane proton-translocating adenosine triphosphatase and K(+) accumulation in guard cells, which is the same mechanism operating in stomata of angiosperms. These results suggest that the early vascular plants respond to both RL and BL and actively regulate stomatal aperture. We also found three plant species that absolutely require BL for both stomatal opening and photosynthetic CO2 fixation, including a gymnosperm, C. revoluta, and the ferns Equisetum hyemale and Psilotum nudum. © 2015 American Society of Plant Biologists. All Rights Reserved.

  1. Early Age Fracture Mechanics and Cracking of Concrete

    DEFF Research Database (Denmark)

    Østergaard, Lennart

    2003-01-01

    . The reasons are the increased autogenous deformation, the high rate of heat evolution and a higher brittleness of these concretes. Due to these adverse mechanisms the interest in the full description of the behavior of early age concrete has increased dramatically in the last two or three decades. Almost all...... the fictitious crack model and the aim has been experimentally to determine the fracture mechanical properties related to this model. The results provide interesting and important insight into the development of the fracture properties in early age. It is found that the characteristic length has moments of low...... values in early age, which means that the cracking sensibility is higher at those time points. The possible influence of time-dependent effects in the fracture mechanical properties on the cracking behavior in early age has also been investigated. The reason for this has been the known fact...

  2. Mechanical response of biopolymer double networks

    Science.gov (United States)

    Carroll, Joshua; Das, Moumita

    We investigate a double network model of articular cartilage (AC) and characterize its equilibrium mechanical response. AC has very few cells and the extracellular matrix mainly determines its mechanical response. This matrix can be thought of as a double polymer network made of collagen and aggrecan. The collagen fibers are stiff and resist tension and compression forces, while aggrecans are flexible and control swelling and hydration. We construct a microscopic model made of two interconnected disordered polymer networks, with fiber elasticity chosen to qualitatively mimic the experimental system. We study the collective mechanical response of this double network as a function of the concentration and stiffness of the individual components as well as the strength of the connection between them using rigidity percolation theory. Our results may provide a better understanding of mechanisms underlying the mechanical resilience of AC, and more broadly may also lead to new perspectives on the mechanical response of multicomponent soft materials. This work was partially supported by a Cottrell College Science Award.

  3. Predictive information processing is a fundamental learning mechanism present in early development: evidence from infants.

    Science.gov (United States)

    Trainor, Laurel J

    2012-02-01

    Evidence is presented that predictive coding is fundamental to brain function and present in early infancy. Indeed, mismatch responses to unexpected auditory stimuli are among the earliest robust cortical event-related potential responses, and have been measured in young infants in response to many types of deviation, including in pitch, timing, and melodic pattern. Furthermore, mismatch responses change quickly with specific experience, suggesting that predictive coding reflects a powerful, early-developing learning mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    Science.gov (United States)

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  5. The Cytoskeleton and Force Response Mechanisms

    Science.gov (United States)

    Allen, Philip Goodwin

    2003-01-01

    The long term aim of this project was to define the mechanisms by which cells sense and respond to the physical forces experienced at 1g and missing in microgravity. Identification and characterization of the elements of the cells force response mechanism could provide pathways and molecules to serve as targets for pharmacological intervention to mitigate the pathologic effects of microgravity. Mechanical forces experienced by the organism can be transmitted to cells through molecules that allow cells to bind to the extracellular matrix and through other types of molecules which bind cells to each other. These molecules are coupled in large complexes of proteins to structural elements such as the actin cytoskeleton that give the cell the ability to sense, resist and respond to force. Application of small forces to tissue culture cells causes local elevation of intracellular calcium through stretch activated ion channels, increased tyrosine phosphorylation and a restructuring of the actin cytoskeleton. Using collagen coated iron oxide beads and strong magnets, we can apply different levels of force to cells in culture. We have found that force application causes the cells to polymerize actin at the site of mechanical deformation and unexpectedly, to depolymerize actin across the rest of the cell. Observations of GFP- actin expressing cells demonstrate that actin accumulates at the site of deformation within the first five minutes of force application and is maintained for many tens of minutes after force is removed. Consistent with the reinforcement of the cytoskeletal structures underlying the integrin-bead interaction, force also alters the motion of bound magnetic beads. This effect is seen following the removal of the magnetic field, and is only partially ablated by actin disruption with cytochalsin B. While actin is polymerizing locally at the site of force application, force also stimulates a global reduction in actin filament content within the cells. We have

  6. The origins of cognitive vulnerability in early childhood: mechanisms linking early attachment to later depression.

    Science.gov (United States)

    Morley, Tara E; Moran, Greg

    2011-11-01

    This paper examines the theory and research linking attachment relationships to cognitive vulnerability to depression and assesses evidence that early attachment experiences contribute to the development of these cognitive processes. Most research in this area has involved adult participants using self-report measures of both attachment and depressive vulnerabilities and thus cannot convincingly speak to the existence of such a developmental pathway. Several studies, however, have followed individuals from infancy and examined the emergence of self-esteem and responses to failure throughout childhood and adolescence. These studies suggest that early experiences in non-secure attachment relationships place an individual at-risk for developing a cognitive framework that increases their vulnerability to depression following stressful life events. The paper concludes with a discussion of how future research might best explore specific mechanisms through which distinct attachment relationships may lead to divergent developmental pathways sharing the common outcome of cognitive processes that place individuals at risk for depression. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2014-05-01

    Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

  8. Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

    2014-01-01

    Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

  9. Respiratory mechanics in ventilated preterm infants : early determinants and outcome

    NARCIS (Netherlands)

    Snepvangers, Dimphn Adriana Cornelia Maria

    2003-01-01

    The studies in this thesis show that in the current surfactant era, the majority of ventilated preterm infants are still suffering from respiratory morbidity and substantial respiratory function abnormalities throughout the early years of life. Since respiratory function testing during mechanical

  10. Analysis of the thermo-chemo-mechanical behavior of massive concrete structures oat early-age

    International Nuclear Information System (INIS)

    Honorio, T.; Bary, B.; Benboudjema, F.

    2014-01-01

    The prediction of the thermo-chemo-mechanical behavior of concrete structures at early ages is important in the context of the feasibility of massive structures. Different phenomena affecting the thermal response of the structure are studied, namely the influence of the change on convection conditions due to wind, the influence of solar radiation, the influence of ambient temperature and the influence of assembly date. A mechanical analysis accounting for autogenous shrinkage and creep strains, besides thermal strains, is performed for the latter case. The results point out the importance of considering the solar radiation and wind conditions on the thermal response of the structure. The ambient temperature impacts directly the maximum temperature reached within the structure. Finally, although the temperature profiles seem just to shift according to the assembly date, the mechanical response is less favorable to early assembly dates. (authors)

  11. Robert Hooke: early respiratory physiologist, polymath, and mechanical genius.

    Science.gov (United States)

    West, John B

    2014-07-01

    Robert Hooke (1635-1703) was a polymath who made important contributions to respiratory physiology and many other scientific areas. With Robert Boyle, he constructed the first air pump that allowed measurements on small animals at a reduced atmospheric pressure, and this started the discipline of high-altitude physiology. He also built the first human low-pressure chamber and described his experiences when the pressure was reduced to the equivalent of an altitude of ∼2,400 m. Using artificial ventilation in an animal preparation, he demonstrated that movement of the lung was not essential for life. His book Micrographia describing early studies with a microscope remains a classic. He produced an exquisite drawing of the head of a fly, showing the elaborate compound eye. There is also a detailed drawing of a flea, and Hooke noted how the long, many-jointed legs enable the insect to jump so high. For 40 years, he was the curator of experiments for the newly founded Royal Society in London and contributed greatly to its intellectual ferment. His mechanical inventions covered an enormous range, including the watch spring, the wheel barometer, and the universal joint. Following the Great Fire of London in 1666, he designed many of the new buildings in conjunction with Christopher Wren. Unfortunately, Hooke had an abrasive personality, which was partly responsible for a lack of recognition of his work for many years. However, during the last 25 years, there has been renewed interest, and he is now recognized as a brilliant scientist and innovator. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

  12. Epigenomic mechanisms of early adversity and HPA dysfunction: Considerations for PTSD research

    Directory of Open Access Journals (Sweden)

    Patrick O McGowan

    2013-09-01

    Full Text Available Childhood adversity can have life-long consequences for the response to stressful events later in life. Abuse or severe neglect are well known risk factors for post-traumatic stress disorder (PTSD, at least in part via changes in neural systems mediating the endocrine response to stress. Determining the biological signatures of risk for stress-related mental disorders such as PTSD is important for identifying homogenous subgroups and improving treatment options. This review will focus on epigenetic regulation in early life by adversity and parental care – prime mediators of offspring neurodevelopment - in order to address several questions: (1 what have studies of humans and analogous animal models taught us about molecular mechanisms underlying changes in stress-sensitive physiological systems in response to early life trauma? (2 What are the considerations for studies relating early adversity and PTSD risk, going forward? I will summarize studies in animals and humans that address the epigenetic response to early adversity in the brain and in peripheral tissues. In so doing, I will describe work on the Glucocorticoid Receptor (GR and other well-characterized genes within the stress response pathway and then turn to genomic studies to illustrate the use of increasingly powerful high-throughput approaches to the study of epigenomic mechanisms.

  13. Exploring early public responses to geoengineering.

    Science.gov (United States)

    Pidgeon, Nick; Corner, Adam; Parkhill, Karen; Spence, Alexa; Butler, Catherine; Poortinga, Wouter

    2012-09-13

    Proposals for geoengineering the Earth's climate are prime examples of emerging or 'upstream' technologies, because many aspects of their effectiveness, cost and risks are yet to be researched, and in many cases are highly uncertain. This paper contributes to the emerging debate about the social acceptability of geoengineering technologies by presenting preliminary evidence on public responses to geoengineering from two of the very first UK studies of public perceptions and responses. The discussion draws upon two datasets: qualitative data (from an interview study conducted in 42 households in 2009), and quantitative data (from a subsequent nationwide survey (n=1822) of British public opinion). Unsurprisingly, baseline awareness of geoengineering was extremely low in both cases. The data from the survey indicate that, when briefly explained to people, carbon dioxide removal approaches were preferred to solar radiation management, while significant positive correlations were also found between concern about climate change and support for different geoengineering approaches. We discuss some of the wider considerations that are likely to shape public perceptions of geoengineering as it enters the media and public sphere, and conclude that, aside from technical considerations, public perceptions are likely to prove a key element influencing the debate over questions of the acceptability of geoengineering proposals.

  14. Early mechanical stimulation only permits timely bone healing in sheep.

    Science.gov (United States)

    Tufekci, Pelin; Tavakoli, Aramesh; Dlaska, Constantin; Neumann, Mirjam; Shanker, Mihir; Saifzadeh, Siamak; Steck, Roland; Schuetz, Michael; Epari, Devakar

    2018-06-01

    Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano-sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological-like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro-computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological-like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well-defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under-stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1790-1796, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. The Mechanical Response of Multifunctional Battery Systems

    Science.gov (United States)

    Tsutsui, Waterloo

    The current state of the art in the field of the mechanical behavior of electric vehicle (EV) battery cells is limited to quasi-static analysis. The lack of published data in the dynamic mechanical behavior of EV battery cells blinds engineers and scientists with the uncertainty of what to expect when EVs experience such unexpected events as intrusions to their battery systems. To this end, the recent occurrences of several EVs catching fire after hitting road debris even make this topic timelier. In order to ensure the safety of EV battery, it is critical to develop quantitative understanding of battery cell mechanical behavior under dynamic compressive loadings. Specifically, the research focuses on the dynamic mechanical loading effect on the standard "18650" cylindrical lithium-ion battery cells. In the study, the force-displacement and voltage-displacement behavior of the battery cells were analyzed experimentally at two strain rates, two state-of-charges, and two unit-cell configurations. The results revealed the strain rate sensitivity of their mechanical responses with the solid sacrificial elements. When the hollow sacrificial cells are used, on the other hand, effect was negligible up to the point of densification strength. Also, the high state-of-charge appeared to increase the stiffness of the battery cells. The research also revealed the effectiveness of the sacrificial elements on the mechanical behavior of a unit cell that consists of one battery cell and six sacrificial elements. The use of the sacrificial elements resulted in the delayed initiation of electric short circuit. Based on the analysis of battery behavior at the cell level, granular battery assembly, a battery pack, was designed and fabricated. The behavior of the granular battery assembly was analyzed both quasistatically and dynamically. Building on the results of the research, various research plans were proposed. Through conducting the research, we sought to answer the following

  16. Early mechanisms in radiation-induced biological damage

    International Nuclear Information System (INIS)

    Powers, E.L.

    1983-01-01

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical

  17. Computational mechanics of nonlinear response of shells

    Energy Technology Data Exchange (ETDEWEB)

    Kraetzig, W.B. (Bochum Univ. (Germany, F.R.). Inst. fuer Statik und Dynamik); Onate, E. (Universidad Politecnica de Cataluna, Barcelona (Spain). Escuela Tecnica Superior de Ingenieros de Caminos) (eds.)

    1990-01-01

    Shell structures and their components are utilized in a wide spectrum of engineering fields reaching from space and aircraft structures, pipes and pressure vessels over liquid storage tanks, off-shore installations, cooling towers and domes, to bodyworks of motor vehicles. Of continuously increasing importance is their nonlinear behavior, in which large deformations and large rotations are involved as well as nonlinear material properties. The book starts with a survey about nonlinear shell theories from the rigorous point of view of continuum mechanics, this starting point being unavoidable for modern computational concepts. There follows a series of papers on nonlinear, especially unstable shell responses, which draw computational connections to well established tools in the field of static and dynamic stability of systems. Several papers are then concerned with new finite element derivations for nonlinear shell problems, and finally a series of authors contribute to specific applications opening a small window of the above mentioned wide spectrum. (orig./HP) With 159 figs.

  18. Computational mechanics of nonlinear response of shells

    International Nuclear Information System (INIS)

    Kraetzig, W.B.; Onate, E.

    1990-01-01

    Shell structures and their components are utilized in a wide spectrum of engineering fields reaching from space and aircraft structures, pipes and pressure vessels over liquid storage tanks, off-shore installations, cooling towers and domes, to bodyworks of motor vehicles. Of continuously increasing importance is their nonlinear behavior, in which large deformations and large rotations are involved as well as nonlinear material properties. The book starts with a survey about nonlinear shell theories from the rigorous point of view of continuum mechanics, this starting point being unavoidable for modern computational concepts. There follows a series of papers on nonlinear, especially unstable shell responses, which draw computational connections to well established tools in the field of static and dynamic stability of systems. Several papers are then concerned with new finite element derivations for nonlinear shell problems, and finally a series of authors contribute to specific applications opening a small window of the above mentioned wide spectrum. (orig./HP) With 159 figs

  19. The mechanisms for social and environmentally responsible agricultural land use

    OpenAIRE

    Ye. Mishenin; I. Yarova

    2015-01-01

    This paper deals with arguments that the most effective mechanism for greening use of land resources is to increase the level of social and environmental responsibility. The mechanisms for social and environmentally responsible agricultural land use are formed.

  20. Early growth and postprandial appetite regulatory hormone responses

    DEFF Research Database (Denmark)

    Perälä, Mia-Maria; Kajantie, Eero; Valsta, Liisa M

    2013-01-01

    Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore......, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life......, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels....

  1. Language experience enhances early cortical pitch-dependent responses

    Science.gov (United States)

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Vijayaraghavan, Venkatakrishnan

    2014-01-01

    Pitch processing at cortical and subcortical stages of processing is shaped by language experience. We recently demonstrated that specific components of the cortical pitch response (CPR) index the more rapidly-changing portions of the high rising Tone 2 of Mandarin Chinese, in addition to marking pitch onset and sound offset. In this study, we examine how language experience (Mandarin vs. English) shapes the processing of different temporal attributes of pitch reflected in the CPR components using stimuli representative of within-category variants of Tone 2. Results showed that the magnitude of CPR components (Na-Pb and Pb-Nb) and the correlation between these two components and pitch acceleration were stronger for the Chinese listeners compared to English listeners for stimuli that fell within the range of Tone 2 citation forms. Discriminant function analysis revealed that the Na-Pb component was more than twice as important as Pb-Nb in grouping listeners by language affiliation. In addition, a stronger stimulus-dependent, rightward asymmetry was observed for the Chinese group at the temporal, but not frontal, electrode sites. This finding may reflect selective recruitment of experience-dependent, pitch-specific mechanisms in right auditory cortex to extract more complex, time-varying pitch patterns. Taken together, these findings suggest that long-term language experience shapes early sensory level processing of pitch in the auditory cortex, and that the sensitivity of the CPR may vary depending on the relative linguistic importance of specific temporal attributes of dynamic pitch. PMID:25506127

  2. Mechanical origins of rightward torsion in early chick brain development

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

    2015-03-01

    During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

  3. Early adversity and brain response to faces in young adulthood.

    Science.gov (United States)

    Lieslehto, Johannes; Kiviniemi, Vesa; Mäki, Pirjo; Koivukangas, Jenni; Nordström, Tanja; Miettunen, Jouko; Barnett, Jennifer H; Jones, Peter B; Murray, Graham K; Moilanen, Irma; Paus, Tomáš; Veijola, Juha

    2017-09-01

    Early stressors play a key role in shaping interindividual differences in vulnerability to various psychopathologies, which according to the diathesis-stress model might relate to the elevated glucocorticoid secretion and impaired responsiveness to stress. Furthermore, previous studies have shown that individuals exposed to early adversity have deficits in emotion processing from faces. This study aims to explore whether early adversities associate with brain response to faces and whether this association might associate with the regional variations in mRNA expression of the glucocorticoid receptor gene (NR3C1). A total of 104 individuals drawn from the Northern Finland Brith Cohort 1986 participated in a face-task functional magnetic resonance imaging (fMRI) study. A large independent dataset (IMAGEN, N = 1739) was utilized for reducing fMRI data-analytical space in the NFBC 1986 dataset. Early adversities were associated with deviant brain response to fearful faces (MANCOVA, P = 0.006) and with weaker performance in fearful facial expression recognition (P = 0.01). Glucocorticoid receptor gene expression (data from the Allen Human Brain Atlas) correlated with the degree of associations between early adversities and brain response to fearful faces (R 2  = 0.25, P = 0.01) across different brain regions. Our results suggest that early adversities contribute to brain response to faces and that this association is mediated in part by the glucocorticoid system. Hum Brain Mapp 38:4470-4478, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. MECHANISMS OF IMMUNE RESPONSES IN CNIDARIANS

    Directory of Open Access Journals (Sweden)

    Iván Darío Ocampo

    2015-05-01

    Full Text Available The immune system maintains the integrity of the organisms through a complex network of molecules, cells, and tissues that recognize internal or external antigenic substances to neutralized and eliminate them. The mechanisms of immune response have evolved in a modular fashion, where members of a given module interact strongly among them, but weakly with members of other modules, providing robustness and evolvability to the immune system. Ancestral modules are the raw material for the generation of new modules through evolution. Thus, the study of immune systems in basal metazoans such as cnidarians seeks to determine the basic tool kit from which the metazoans started to construct their immune systems. In addition, understanding the immune mechanisms in cnidarians contributes to decipher the etiopathology of coral diseases of infectious nature that are affecting coral reefs worldwide. RESUMEN El sistema inmune mantiene la integridad de los organismos vivos por medio de una red compleja de moléculas, células y tejidos que reconocen sustancias antigénicas internas o externas para neutralizarlas y eliminarlas. Los mecanismos de respuesta inmune han evolucionado de una manera modular, en donde miembros de un módulo dado interactúan fuertemente entre sí, pero débilmente con componentes de otros módulos, otorgando así robustez y potencial evolutivo al sistema inmune. Módulos ancestrales representan el material básico para la generación de nuevos módulos durante el proceso evolutivo. Así, el estudio de sistemas inmunes en metazoarios basales como los cnidarios busca determinar cuales son los módulos ancestrales a partir de los cuales se constituyen los sistemas inmunes de animales derivados. Adicionalmente, el entendimiento de los mecanismos de respuesta inmune en cnidarios eventualmente contribuirá a descifrar la etiopatología de las enfermedades de corales de carácter infeccioso que está afectando los corales en el mundo.

  5. Early response to psychological trauma--what GPs can do.

    Science.gov (United States)

    Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

    2013-09-01

    There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

  6. Serological response to Epstein-Barr virus early antigen is ...

    African Journals Online (AJOL)

    Serological response to Epstein-Barr virus early antigen is associated with gastric cancer and human immunodeficiency virus infection in Zambian adults: a ... EBV exposure is common among Zambian adults and that EBV EA seropositivity is associated with gastric cancer and HIV infection, but not premalignant lesions.

  7. The early medical response to the Goiania accident

    International Nuclear Information System (INIS)

    Valverde, N.J.; Oliveira, A.R.

    2000-01-01

    The Goiania accident was the most severe radiological one that ever happened in the western hemisphere. The response to its human, social, environmental, economical and psychological burdens represented a huge challenge. Thanks to a multi-institutional intervention the consequences of the accident were greatly minimised. The medical response followed the same pattern and was based on a three-level system of progressive assistance. The early medical response encompassed medical and 'radiological' triage, admission to a specially prepared ward of a local hospital and treatment at a reference center in Rio de Janeiro. (author)

  8. Decisional responsibility for mechanical ventilation and weaning

    DEFF Research Database (Denmark)

    Rose, Louise; Blackwood, Bronagh; Egerod, Ingrid

    2011-01-01

    Optimal management of mechanical ventilation and weaning requires dynamic and collaborative decision making to minimize complications and avoid delays in the transition to extubation. In the absence of collaboration, ventilation decision making may be fragmented, inconsistent, and delayed. Our...

  9. Evolution of attention mechanisms for early visual processing

    Science.gov (United States)

    Müller, Thomas; Knoll, Alois

    2011-03-01

    Early visual processing as a method to speed up computations on visual input data has long been discussed in the computer vision community. The general target of a such approaches is to filter nonrelevant information from the costly higher-level visual processing algorithms. By insertion of this additional filter layer the overall approach can be speeded up without actually changing the visual processing methodology. Being inspired by the layered architecture of the human visual processing apparatus, several approaches for early visual processing have been recently proposed. Most promising in this field is the extraction of a saliency map to determine regions of current attention in the visual field. Such saliency can be computed in a bottom-up manner, i.e. the theory claims that static regions of attention emerge from a certain color footprint, and dynamic regions of attention emerge from connected blobs of textures moving in a uniform way in the visual field. Top-down saliency effects are either unconscious through inherent mechanisms like inhibition-of-return, i.e. within a period of time the attention level paid to a certain region automatically decreases if the properties of that region do not change, or volitional through cognitive feedback, e.g. if an object moves consistently in the visual field. These bottom-up and top-down saliency effects have been implemented and evaluated in a previous computer vision system for the project JAST. In this paper an extension applying evolutionary processes is proposed. The prior vision system utilized multiple threads to analyze the regions of attention delivered from the early processing mechanism. Here, in addition, multiple saliency units are used to produce these regions of attention. All of these saliency units have different parameter-sets. The idea is to let the population of saliency units create regions of attention, then evaluate the results with cognitive feedback and finally apply the genetic mechanism

  10. Individual responsibility in early detection of prostate gland cancer

    International Nuclear Information System (INIS)

    Nodal Laugart, Ramon Lemay; Rodriguez Ardi, Maricel; Tamayo Tamayo, Iser

    2011-01-01

    Starting from the point that morbidity and mortality rate due to prostate gland cancer has increased in Santiago de Cuba, the authors of this work decided to analyze the relation to individual responsibility in order to early detect the aforementioned condition. Therefore, 48 men over 50 years old belonging to the health area of Frank Pais Garcia University Polyclinic in Santiago de Cuba were surveyed during the first months of the year 2011 to determine the factors that influenced on the low risk perception. Results showed the urgent need of carrying out actions of health promotion and disease prevention in order to achieve the individual feels more responsible of his health care. Of the case material, 85,4 % participants admitted they did not have the tests to guarantee the early diagnosis or detect this tumor.(author)

  11. Evaluation of early imaging response criteria in glioblastoma multiforme

    International Nuclear Information System (INIS)

    Gladwish, Adam; Koh, Eng-Siew; Hoisak, Jeremy; Lockwood, Gina; Millar, Barbara-Ann; Mason, Warren; Yu, Eugene; Laperriere, Normand J; Ménard, Cynthia

    2011-01-01

    Early and accurate prediction of response to cancer treatment through imaging criteria is particularly important in rapidly progressive malignancies such as Glioblastoma Multiforme (GBM). We sought to assess the predictive value of structural imaging response criteria one month after concurrent chemotherapy and radiotherapy (RT) in patients with GBM. Thirty patients were enrolled from 2005 to 2007 (median follow-up 22 months). Tumor volumes were delineated at the boundary of abnormal contrast enhancement on T1-weighted images prior to and 1 month after RT. Clinical Progression [CP] occurred when clinical and/or radiological events led to a change in chemotherapy management. Early Radiologic Progression [ERP] was defined as the qualitative interpretation of radiological progression one month post-RT. Patients with ERP were determined pseudoprogressors if clinically stable for ≥6 months. Receiver-operator characteristics were calculated for RECIST and MacDonald criteria, along with alternative thresholds against 1 year CP-free survival and 2 year overall survival (OS). 13 patients (52%) were found to have ERP, of whom 5 (38.5%) were pseudoprogressors. Patients with ERP had a lower median OS (11.2 mo) than those without (not reached) (p < 0.001). True progressors fared worse than pseudoprogressors (median survival 7.2 mo vs. 19.0 mo, p < 0.001). Volume thresholds performed slightly better compared to area and diameter thresholds in ROC analysis. Responses of > 25% in volume or > 15% in area were most predictive of OS. We show that while a subjective interpretation of early radiological progression from baseline is generally associated with poor outcome, true progressors cannot be distinguished from pseudoprogressors. In contrast, the magnitude of early imaging volumetric response may be a predictive and quantitative metric of favorable outcome

  12. Universal biology and the statistical mechanics of early life

    Science.gov (United States)

    Goldenfeld, Nigel; Biancalani, Tommaso; Jafarpour, Farshid

    2017-11-01

    All known life on the Earth exhibits at least two non-trivial common features: the canonical genetic code and biological homochirality, both of which emerged prior to the Last Universal Common Ancestor state. This article describes recent efforts to provide a narrative of this epoch using tools from statistical mechanics. During the emergence of self-replicating life far from equilibrium in a period of chemical evolution, minimal models of autocatalysis show that homochirality would have necessarily co-evolved along with the efficiency of early-life self-replicators. Dynamical system models of the evolution of the genetic code must explain its universality and its highly refined error-minimization properties. These have both been accounted for in a scenario where life arose from a collective, networked phase where there was no notion of species and perhaps even individuality itself. We show how this phase ultimately terminated during an event sometimes known as the Darwinian transition, leading to the present epoch of tree-like vertical descent of organismal lineages. These examples illustrate concrete examples of universal biology: the quest for a fundamental understanding of the basic properties of living systems, independent of precise instantiation in chemistry or other media. This article is part of the themed issue 'Reconceptualizing the origins of life'.

  13. Possible relationships between the early inflammatory response and subsequent fibrosis in rat skin after irradiation

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1975-01-01

    The possible mechanistic relationships between the early inflammatory response and subsequent fibrosis seen after radiation exposure was studied in rats were given single x ray doses of either 2000 or 5000 rads to standardized fields of the inner thigh. The results suggest that two mechanisms are responsible for the radiation-induced increase in extravasation rate and vascular injury seen early after irradiation. First, direct cytocidal damage of the endothelium; and second, chemically mediated, possibly complement dependent mechanisms. Indirect histological evidence suggests a correlation between the PMN infiltrate and the indirect vascular damage. In addition, one may conclude from these data that both direct and indirect damage to the vasculature play a role in influencing the subsequent late radiation-induced fibrosis; and a decrease in the indirect damage may allow the maintenance of a supportive vasculature at lower doses or allow the reestablishment of a vascular bed in the case of higher doses. (U.S.)

  14. Meso Mechanical Analysis of AC Mixture Response

    NARCIS (Netherlands)

    Woldekidan, M.F.; Huurman, M.; Vaccari, E.; Poot, M.

    2012-01-01

    Ongoing research into performance modeling of Asphalt Concrete (AC) mixtures using meso mechanics approaches is being undertaken at Delft University of Technology (TUD). The approach has already been successfully employed for evaluating the long term performance of porous asphalt concrete. The work

  15. Pathways to Conscience: Early Mother-Child Mutually Responsive Orientation and Children's Moral Emotion, Conduct, and Cognition

    Science.gov (United States)

    Kochanska, Grazyna; Forman, David R.; Aksan, Nazan; Dunbar, Stephen B.

    2005-01-01

    Background: Associations between early mother-child mutually responsive orientation (MRO) and children's conscience have been previously established, but the mechanisms accounting for those links are not understood. We examined three such mediational mechanisms: (a) the child's enhanced enjoyment of interactions with the mother, (b) increased…

  16. Generic Primary Mechanical Response of Viscous Liquids

    Science.gov (United States)

    Bierwirth, S. Peter; Böhmer, Roland; Gainaru, Catalin

    2017-12-01

    Four decades ago a seminal review by Jonscher [Nature (London) 267, 673 (1977), 10.1038/267673a0] revealed that the dielectric response of conducting materials is characterized by a "remarkable universality". Demonstrating that the same response pattern is exhibited also by shear rheological spectra of nonpolymeric viscous liquids, the present contribution connects two branches of condensed matter physics: Concepts developed for charge transport can be employed for the description of mass flow and vice versa. Based on the virtual equivalence of the two dynamics a connection is established between microscopic and macroscopic viscoelastic characteristics of liquids, resembling the Barton-Nakajima-Namikawa relation for conductivity.

  17. Neurochemical mechanisms underlying responses to psychostimulants

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.S.; Hitzemann, R.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York, Stony Brook, NY (United States)

    1994-11-01

    This study employed positron emission tomography (PET) to investigate biochemical and metabolic characteristics of the brain of individuals which could put them at risk for drug addiction. It takes advantage of the normal variability between individuals in response to psychoactive drugs to investigate relation between mental state, brain neurochemistry and metabolism and the behavioral response to drugs. We discuss its use to assess if there is an association between mental state and dompaminergic reactivity in response to the psychostimulant drug methylphenidate (MP). Changes in synaptic dopamine induced by MP were evaluated with PET and [11C]raclopride, a D{sub 2} receptor radioligand that is sensitive to endogenous dopamine. Methylpphenidate significantly decreased striatal [11C]raclopride binding. The study showed a correlation between the magnitude of the dopamine-induced changes by methylphenidate, and the mental state of the subjects. Subjects reporting high levels of anxiety and restlessness at baseline had larger changes in MP-induced dopamine changes than those that did not. Further investigations on the relation between an individual`s response to a drug and his/her mental state and personality as well as his neurochemical brain composition may enable to understand better differences in drug addiction vulnerability.

  18. Gelation And Mechanical Response of Patchy Rods

    Science.gov (United States)

    Kazem, Navid; Majidi, Carmel; Maloney, Craig

    We perform Brownian Dynamics simulations to study the gelation of suspensions of attractive, rod-like particles. We show that details of the particle-particle interactions can dramatically affect the dynamics of gelation and the structure and mechanics of the networks that form. If the attraction between the rods is perfectly smooth along their length, they will collapse into compact bundles. If the attraction is sufficiently corrugated or patchy, over time, a rigid space spanning network forms. We study the structure and mechanical properties of the networks that form as a function of the fraction of the surface that is allowed to bind. Surprisingly, the structural and mechanical properties are non-monotonic in the surface coverage. At low coverage, there are not a sufficient number of cross-linking sites to form networks. At high coverage, rods bundle and form disconnected clusters. At intermediate coverage, robust networks form. The elastic modulus and yield stress are both non-monotonic in the surface coverage. The stiffest and strongest networks show an essentially homogeneous deformation under strain with rods re-orienting along the extensional axis. Weaker, clumpy networks at high surface coverage exhibit relatively little re-orienting with strong non-affine deformation. These results suggest design strategies for tailoring surface interactions between rods to yield rigid networks with optimal properties. National Science Foundation and the Air Force Office of Scientific Research.

  19. Host response mechanisms in periodontal diseases

    Directory of Open Access Journals (Sweden)

    Nora SILVA

    2015-06-01

    Full Text Available Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells. Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs and bone-resorbing osteoclasts (OCLs. This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as

  20. Host response mechanisms in periodontal diseases

    Science.gov (United States)

    SILVA, Nora; ABUSLEME, Loreto; BRAVO, Denisse; DUTZAN, Nicolás; GARCIA-SESNICH, Jocelyn; VERNAL, Rolando; HERNÁNDEZ, Marcela; GAMONAL, Jorge

    2015-01-01

    Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts (OCLs). This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as a stage that

  1. Dynamic response analysis as a tool for investigating transport mechanisms

    International Nuclear Information System (INIS)

    Dudok de Wit, Th.; Joye, B.; Lister, J.B.; Moret, J.M.

    1990-01-01

    Dynamic response analysis provides an attractive method for studying transport mechanisms in tokamak plasmas. The analysis of the radial response has already been widely used for heat and particle transport studies. The frequency dependence of the dynamic response, which is often omitted, reveals further properties of the dominant transport mechanisms. Extended measurements of the soft X-ray emission were carried out on the TCA tokamak in order to determine the underlying transport processes. (author) 5 refs., 2 figs

  2. Early life adversity influences stress response association with smoking relapse.

    Science.gov (United States)

    al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

    2017-11-01

    We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

  3. Early-life inflammation, immune response and ageing.

    Science.gov (United States)

    Khan, Imroze; Agashe, Deepa; Rolff, Jens

    2017-03-15

    Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

  4. Mechanisms of quinolone action and microbial response.

    Science.gov (United States)

    Hawkey, Peter M

    2003-05-01

    Over the years, chromosomal mapping of the bacterial genome of Escherichia coli has demonstrated that many loci are associated with quinolone resistance, which is mainly a result of chromosomal mutation or alteration of the quantity or type of porins in the outer membrane of Gram-negative bacteria. There has been one report of a small and confined episode of plasmid-mediated resistance to fluoroquinolones, which did not appear to persist. With the increasingly widespread use of an expanding range of fluoroquinolone antibiotics, a range and mix in individual bacterial isolates of the different mechanisms of resistance to fluoroquinolones will undoubtedly be encountered amongst clinically significant bacteria. Currently, transferable resistance is extremely rare and most resistant bacteria arise from clonal expansion of mutated strains. However, it is conceivable that in the future, horizontal gene transfer may become a more important means of conferring resistance to fluoroquinolones.

  5. Early inflammatory response in rat brain after peripheral thermal injury.

    Science.gov (United States)

    Reyes, Raul; Wu, Yimin; Lai, Qin; Mrizek, Michael; Berger, Jamie; Jimenez, David F; Barone, Constance M; Ding, Yuchuan

    2006-10-16

    Previous studies have shown that the cerebral complications associated with skin burn victims are correlated with brain damage. The aim of this study was to determine whether systemic thermal injury induces inflammatory responses in the brain. Sprague Dawley rats (n=28) were studied in thermal injury and control groups. Animals from the thermal injury (n=14) and control (n=14) group were anesthetized and submerged to the neck vertically in 85 degrees C water for 6 s producing a third degree burn affecting 60-70% of the animal body surface area. The controls were submerged in 37 degrees C water for 6 s. Early expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and intracellular cell adhesion molecules (ICAM-1) protein levels in serum were determined at 3 (n=7) and 7 h (n=7) by enzyme-linked immunoabsorbent assay (ELISA). mRNA of TNF-alpha, IL-1beta, and ICAM-1 in the brain was measured at the same time points with a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). An equal animal number was used for controls. Systemic inflammatory responses were demonstrated by dramatic up-regulations (5-50 fold) of TNF-alpha, IL-1beta, and ICAM-1 protein level in serum at 7 h after the thermal injury. However, as early as 3 h after peripheral thermal injury, a significant increase (3-15 fold) in mRNA expression of TNF-alpha, IL-1beta and ICAM-1 was observed in brain homogenates, with increased levels remaining at 7 h after injury. This study demonstrated an early inflammatory response in the brain after severe peripheral thermal injury. The cerebral inflammatory reaction was associated with expression of systemic cytokines and an adhesion molecule.

  6. Early Flowering as a Drought Escape Mechanism in Plants: How Can It Aid Wheat Production?

    Directory of Open Access Journals (Sweden)

    Yuri Shavrukov

    2017-11-01

    Full Text Available Drought escape (DE is a classical adaptive mechanism which involves rapid plant development to enable the completion of the full life-cycle prior to a coming drought event. This strategy is widely used in populations of native plants, and is also applicable to cereal crops such as wheat. Early flowering time and a shorter vegetative phase can be very important for wheat production in conditions of terminal drought since this can minimize exposure to dehydration during the sensitive flowering and post-anthesis grain filling periods. A gradual shift toward early flowering has been observed over the last century of wheat breeding in countries with a Mediterranean-type climate and frequent terminal drought. This trend is predicted to continue for wheat production in the coming years in response to global climate warming. The advantage of early flowering wheat is apparent under conditions of impending terminal drought, and modern varieties are significantly more productive due to minimization of the risk associated with drought stress. Under favorable conditions, a short vegetative phase can result in reduced plant biomass due to the reduction in time available for photosynthetic production and seed nutrient accumulation. However, high yield potential has been reported for the development of both shallow and deep roots, representing plasticity in response to drought in combination with the early flowering trait. Wheat productivity can be high both in well-watered and drought-affected field trials, where an efficient strategy of DE was associated with quick growth, yield potential and water use efficiency. Therefore, early flowering provides a promising strategy for the production of advanced drought-adapted wheat cultivars.

  7. Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Scott H Robbins

    2007-08-01

    Full Text Available Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs for cytokine production, preserves the conventional dendritic cell (cDC compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate

  8. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Science.gov (United States)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  9. Proteomic analysis of barley response during early spot blotch infection

    International Nuclear Information System (INIS)

    Al-Daoude, A.; Jawhar, M.; Shoaib, A.; Arabi, M.I.E.

    2015-01-01

    Spot blotch (SB), caused by the fungus Cochliobolus sativus, is a common foliar disease of barley worldwide, but little is known about the host response to infection at the protein level. In this study, a systematic shotgun proteomics approach was chosen to document the early barley response to C. sativus infection. Overall, 28 protein spots were consistently observed as differential in the proteome profiles of the challenged and unchallenged plants. After tryptic digestion, MALDI-TOF/MS analysis and MASCOT database searching identified proteins associated with the defense response including resistance proteins, putative hydrolase, proteinase, kinase and general metabolism and transport proteins. These afford important functions in host resistance and pathogen's inhibition in plants. One of the identified products is a putative NBS-LRR protein which is considered one of the major plant disease resistance proteins identified to date. This work indicates that, in combination with functional genomics, response of barley to challenge by C. sativus involved the recruitment of proteins from various defense pathways.(author)

  10. Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

    Science.gov (United States)

    de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

    2013-06-01

    Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

  11. Early transcriptional response of soybean contrasting accessions to root dehydration.

    Directory of Open Access Journals (Sweden)

    José Ribamar Costa Ferreira Neto

    Full Text Available Drought is a significant constraint to yield increase in soybean. The early perception of water deprivation is critical for recruitment of genes that promote plant tolerance. DeepSuperSAGE libraries, including one control and a bulk of six stress times imposed (from 25 to 150 min of root dehydration for drought-tolerant and sensitive soybean accessions, allowed to identify new molecular targets for drought tolerance. The survey uncovered 120,770 unique transcripts expressed by the contrasting accessions. Of these, 57,610 aligned with known cDNA sequences, allowing the annotation of 32,373 unitags. A total of 1,127 unitags were up-regulated only in the tolerant accession, whereas 1,557 were up-regulated in both as compared to their controls. An expression profile concerning the most representative Gene Ontology (GO categories for the tolerant accession revealed the expression "protein binding" as the most represented for "Molecular Function", whereas CDPK and CBL were the most up-regulated protein families in this category. Furthermore, particular genes expressed different isoforms according to the accession, showing the potential to operate in the distinction of physiological behaviors. Besides, heat maps comprising GO categories related to abiotic stress response and the unitags regulation observed in the expression contrasts covering tolerant and sensitive accessions, revealed the unitags potential for plant breeding. Candidate genes related to "hormone response" (LOX, ERF1b, XET, "water response" (PUB, BMY, "salt stress response" (WRKY, MYB and "oxidative stress response" (PER figured among the most promising molecular targets. Additionally, nine transcripts (HMGR, XET, WRKY20, RAP2-4, EREBP, NAC3, PER, GPX5 and BMY validated by RT-qPCR (four different time points confirmed their differential expression and pointed that already after 25 minutes a transcriptional reorganization started in response to the new condition, with important

  12. Mechanical Responses and Physical Factors of the Fingertip Pulp

    Directory of Open Access Journals (Sweden)

    N. Sakai

    2006-01-01

    Full Text Available The images of the mechanical responses were analysed when the fingertip was pressed against a plateau plate, and the influence of the contact angle on the loading pressure and the mechanical responses was investigated. As a result, as the contact angle was smaller, the change ratios due to the loading pressure were significantly larger in the contact length, the contact width and the distortion of lateral-view area. These parameters were thought to be useful in clinical medicine as indices for the degrees of mechanical responses of the fingertip. The length of the central axis and the maximum width of the fingertip were inappropriate as the parameters to represent the mechanical responses of the fingertip. The maximum width of the fingertip scarcely changed. This does not reflect the compressibility of the fingertip, and the fingertip as a whole extended along the central axis and in the vertical direction, and the change was not reflected in the maximum width.

  13. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    Science.gov (United States)

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  14. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Directory of Open Access Journals (Sweden)

    Gomez-Lopez Nardhy

    2013-01-01

    Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

  15. Evidence for two concurrent inhibitory mechanisms during response preparation

    Science.gov (United States)

    Duque, Julie; Lew, David; Mazzocchio, Riccardo; Olivier, Etienne; Ivry, Richard B.

    2010-01-01

    Inhibitory mechanisms are critically involved in goal-directed behaviors. To gain further insight into how such mechanisms shape motor representations during response preparation, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and H-reflexes were recorded from left hand muscles during choice reaction time tasks. The imperative signal, which indicated the required response, was always preceded by a preparatory cue. During the post-cue delay period, left MEPs were suppressed when the left hand had been cued for the forthcoming response, suggestive of a form of inhibition specifically directed at selected response representations. H-reflexes were also suppressed on these trials, indicating that the effects of this inhibition extend to spinal circuits. In addition, left MEPs were suppressed when the right hand was cued, but only when left hand movements were a possible response option before the onset of the cue. Notably, left hand H-reflexes were not modulated on these trials, consistent with a cortical locus of inhibition that lowers the activation of task-relevant, but non-selected responses. These results suggest the concurrent operation of two inhibitory mechanisms during response preparation: one decreases the activation of selected responses at the spinal level, helping to control when selected movements should be initiated by preventing their premature release; a second, upstream mechanism helps to determine what response to make during a competitive selection process. PMID:20220014

  16. Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

    Science.gov (United States)

    Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

    2014-02-01

    Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

  17. Using physiology and behaviour to understand the responses of fish early life stages to toxicants.

    Science.gov (United States)

    Sloman, K A; McNeil, P L

    2012-12-01

    The use of early life stages of fishes (embryos and larvae) in toxicity testing has been in existence for a long time, generally utilizing endpoints such as morphological defects and mortality. Behavioural endpoints, however, may represent a more insightful evaluation of the ecological effects of toxicants. Indeed, recent years have seen a considerable increase in the use of behavioural measurements in early life stages reflecting a substantial rise in zebrafish Danio rerio early life-stage toxicity testing and the development of automated behavioural monitoring systems. Current behavioural endpoints identified for early life stages in response to toxicant exposure include spontaneous activity, predator avoidance, capture of live food, shoaling ability and interaction with other individuals. Less frequently used endpoints include measurement of anxiogenic behaviours and cognitive ability, both of which are suggested here as future indicators of toxicant disruption. For many simple behavioural endpoints, there is still a need to link behavioural effects with ecological relevance; currently, only a limited number of studies have addressed this issue. Understanding the physiological mechanisms that underlie toxicant effects on behaviour so early in life has received far less attention, perhaps because physiological measurements can be difficult to carry out on individuals of this size. The most commonly established physiological links with behavioural disruption in early life stages are similar to those seen in juveniles and adults including sensory deprivation (olfaction, lateral line and vision), altered neurogenesis and neurotransmitter concentrations. This review highlights the importance of understanding the integrated behavioural and physiological response of early life stages to toxicants and identifies knowledge gaps which present exciting areas for future research. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  18. A predictive control scheme for automated demand response mechanisms

    NARCIS (Netherlands)

    Lampropoulos, I.; Bosch, van den P.P.J.; Kling, W.L.

    2012-01-01

    The development of demand response mechanisms can provide a considerable option for the integration of renewable energy sources and the establishment of efficient generation and delivery of electrical power. The full potential of demand response can be significant, but its exploration still remains

  19. Early inflammatory response in epithelial ovarian tumor cyst fluids

    International Nuclear Information System (INIS)

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-01-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors

  20. A Dynamic Market Mechanism for Markets with Shiftable Demand Response

    DEFF Research Database (Denmark)

    Hansen, Jacob; Knudsen, Jesper Viese; Kiani, Arman

    2014-01-01

    renewables, this mechanism accommodates both consumers with a shiftable Demand Response and an adjustable Demand Response. The overall market mechanism is evaluated in a Day Ahead Market and is shown in a numerical example to result in a reduction of the cost of electricity for the consumer, as well......In this paper, we propose a dynamic market mechanism that converges to the desired market equilibrium. Both locational marginal prices and the schedules for generation and consumption are determined through a negotiation process between the key market players. In addition to incorporating...

  1. Scrambled eggs: mechanical forces as ecological factors in early development.

    Science.gov (United States)

    Moore, Steven W

    2003-01-01

    Many ecological interactions involve, at some level, mechanical forces and the movements or structural deformations they produce. Although the most familiar examples involve the functional morphology of adult structures, all life history stages (not just the adults) are subject to the laws of physics. Moreover, the success of every lineage depends on the success of every life history stage (again, not just the adults). Therefore, insights gained by using mechanical engineering principles and techniques to study ecological interactions between gametes, embryos, larvae, and their environment are essential to a well-rounded understanding of development, ecology, and evolution. Here I draw on examples from the literature and my own research to illustrate ways in which mechanical forces in the environment shape development. These include mechanical forces acting as selective factors (e.g., when coral gamete size and shape interact with turbulent water flow to determine fertilization success) and as developmental cues (e.g., when plant growth responds to gravity or bone growth responds to mechanical loading). I also examine the opposite cause-and-effect relationship by considering examples in which the development of organisms impacts ecologically relevant mechanical forces. Finally, I discuss the potential for ecological pattern formation as a result of feedback loops created by such bidirectional interactions between developmental processes and mechanical forces in the environment.

  2. Perceived decisional responsibility for mechanical ventilation and weaning

    DEFF Research Database (Denmark)

    Haugdahl, Hege S; Storli, Sissel; Rose, Louise

    2014-01-01

    AIM: To explore variability in perceptions of nurse managers and physician directors regarding roles, responsibilities and clinical-decision making related to mechanical ventilator weaning in Norwegian intensive care units (ICUs). BACKGROUND: Effective teamwork is crucial for providing optimal...... patient care in ICU. More knowledge on nurses' and physicians' perceptions of responsibility in clinical decision-making for mechanical ventilation is needed. METHODS: Self-administered survey of mechanical ventilation and weaning responsibilities was sent to nurse managers and physician directors...... of Norwegian adult ICUs. Nurses' decisional influence and autonomy were estimated on a numeric rating scale (NRS) from 0 to 10 (least to most). RESULTS: Response rate was 38/60 (63%) nurses and 38/52 (73%) physicians. On the NRS nurse managers perceived the autonomy and influence of nurses' ventilator...

  3. Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

    Science.gov (United States)

    Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

    2011-01-01

    Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

  4. Early warning systems and rapid response to the deteriorating patient in hospital: A realist evaluation.

    Science.gov (United States)

    McGaughey, Jennifer; O'Halloran, Peter; Porter, Sam; Trinder, John; Blackwood, Bronagh

    2017-12-01

    To test the Rapid Response Systems programme theory against actual practice components of the Rapid Response Systems implemented to identify those contexts and mechanisms which have an impact on the successful achievement of desired outcomes in practice. Rapid Response Systems allow deteriorating patients to be recognized using Early Warning Systems, referred early via escalation protocols and managed at the bedside by competent staff. Realist evaluation. The research design was an embedded multiple case study approach of four wards in two hospitals in Northern Ireland which followed the principles of Realist Evaluation. We used various mixed methods including individual and focus group interviews, observation of nursing practice between June-November 2010 and document analysis of Early Warning Systems audit data between May-October 2010 and hospital acute care training records over 4.5 years from 2003-2008. Data were analysed using NiVivo8 and SPPS. A cross-case analysis highlighted similar patterns of factors which enabled or constrained successful recognition, referral and response to deteriorating patients in practice. Key enabling factors were the use of clinical judgement by experienced nurses and the empowerment of nurses as a result of organizational change associated with implementation of Early Warning System protocols. Key constraining factors were low staffing and inappropriate skill mix levels, rigid implementation of protocols and culturally embedded suboptimal communication processes. Successful implementation of Rapid Response Systems was dependent on adopting organizational and cultural changes that facilitated staff empowerment, flexible implementation of protocols and ongoing experiential learning. © 2017 John Wiley & Sons Ltd.

  5. A linear chromatic mechanism drives the pupillary response.

    Science.gov (United States)

    Tsujimura, S.; Wolffsohn, J. S.; Gilmartin, B.

    2001-01-01

    Previous studies have shown that a chromatic mechanism can drive pupil responses. The aim of this research was to clarify whether a linear or nonlinear chromatic mechanism drives pupillary responses by using test stimuli of various colours that are defined in cone contrast space. The pupil and accommodation responses evoked by these test stimuli were continuously and simultaneously objectively measured by photorefraction. The results with isochromatic and isoluminant stimuli showed that the accommodative level remained approximately constant (< 0.25 D change in mean level) even when the concurrent pupillary response was large (ca. 0.30 mm). The pupillary response to an isoluminant grating was sustained, delayed (by ca. 60 ms) and larger in amplitude than that for a isochromatic uniform stimulus, which supports previous work suggesting that the chromatic mechanism contributes to the pupillary response. In a second experiment, selected chromatic test gratings were used and isoresponse contours in cone contrast space were obtained. The results showed that the isoresponse contour in cone contrast space is well described (r(2) = 0.99) by a straight line with a positive slope. The results indicate that a /L - M/ linear chromatic mechanism, whereby a signal from the long wavelength cone is subtracted from that of the middle wavelength cone and vice versa, drives pupillary responses. PMID:11674867

  6. Mechanisms behind early life nutrition and adult disease outcome

    OpenAIRE

    Velkoska, Elena; Morris, Margaret J

    2011-01-01

    Obesity is increasing around the globe. While adult lifestyle factors undoubtedly contribute to the incidence of obesity and its attendant disorders, mounting evidence suggests that programming of obesity may occur following under- and over-nutrition during development. As hypothalamic control of appetite and energy expenditure is set early in life and can be perturbed by certain exposures such as undernutrition and altered metabolic and hormonal signals, in utero exposure to altered maternal...

  7. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  8. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Peng

    2015-02-27

    Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response.

  9. Mechanical Thrombectomy for Early Treatment of Massive Pulmonary Embolism

    International Nuclear Information System (INIS)

    Reekers, Jim A.; Baarslag, Henk Jan; Koolen, Maria G.J.; Delden, Otto van; Beek, Edwin J.R. van

    2003-01-01

    We report our technique and results of percutaneous mechanical thrombectomy in a consecutive series of eight patients with massive PE. We also discuss the possible role of mechanical PE thrombectomy. Eight consecutive patients with acute massive PE, with or without hemodynamic impairment, were treated with mechanical thrombectomy. We used a modified 7-fr hydrolyzer catheter. The treatment was combined with systemic fibrinolysis. From the logistic and technical point we encountered no problems. All patients showed significant improvement while still in the angiography suite. There were no bleeding complications and no other events related to the procedure. Despite the clinical improvement, one patient died shortly after the procedure from cardiac failure. In all patients there was an acute increase in PO2 to normal values. Only a mean of about 50% of all local thrombus could be removed (range 30-80%). The mean PAP pre-intervention decreased only minimally from 42.5 mmHg to 36.3 mm Hg post-intervention (not significant). In three patients, the PAP continues to remain high at follow-up. The most important feature of mechanical thrombectomy for massive PE is the immediate improvement of the cardiac output, PO2, and clinical situation, overcoming the first critical hours after massive PE. The amount of thrombus reduction seems not to be an important parameter

  10. Early Bilingualism Enhances Mechanisms of False-Belief Reasoning

    Science.gov (United States)

    Kovacs, Agnes Melinda

    2009-01-01

    In their first years, children's understanding of mental states seems to improve dramatically, but the mechanisms underlying these changes are still unclear. Such "theory of mind" (ToM) abilities may arise during development, or have an innate basis, developmental changes reflecting limitations of other abilities involved in ToM tasks (e.g.…

  11. Hypertensive response to exercise: mechanisms and clinical implication

    OpenAIRE

    Kim, Darae; Ha, Jong-Won

    2016-01-01

    A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates tha...

  12. Nociceptive responses to thermal and mechanical stimulations in awake pigs

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S.

    2013-01-01

    body sizes (30 and 60 kg) were exposed to thermal (CO(2) laser) and mechanical (pressure application measurement device) stimulations to the flank and the hind legs in a balanced order. The median response latency and the type of behavioural response were recorded. RESULTS: Small pigs exhibited...... animal studies in a large species require further examination. This manuscript describes the initial development of a porcine model of cutaneous nociception and focuses on interactions between the sensory modality, body size and the anatomical location of the stimulation site. METHODS: Pigs of different...... significantly lower pain thresholds (shorter latency to response) than large pigs to thermal and mechanical stimulations. Stimulations at the two anatomical locations elicited very distinct sets of behavioural responses, with different levels of sensitivity between the flank and the hind legs. Furthermore...

  13. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Sebastian Weckbach

    2012-01-01

    Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

  14. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Science.gov (United States)

    Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

    2012-01-01

    Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

  15. The association between autism and errors in early embryogenesis: what is the causal mechanism?

    NARCIS (Netherlands)

    Ploeger, A.; Raijmakers, M.E.J.; van der Maas, H.L.J.; Galis, F.

    2010-01-01

    The association between embryonic errors and the development of autism has been recognized in the literature, but the mechanism underlying this association remains unknown. We propose that pleiotropic effects during a very early and specific stage of embryonic development—early organogenesis—can

  16. Immunological mechanisms to establish embryo tolerance in early bovine pregnancy.

    Science.gov (United States)

    Groebner, A E; Schulke, K; Schefold, J C; Fusch, G; Sinowatz, F; Reichenbach, H D; Wolf, E; Meyer, H H D; Ulbrich, S E

    2011-01-01

    A well-balanced immunological interaction between mother and the semi-allogenic embryo is of particular importance. The objective of the present study was to analyse mechanisms of immune tolerance in bovine pregnancy during peri-implantation. Simmental heifers inseminated with either cryopreserved spermatozoa or seminal plasma were killed 12, 15 or 18 days after oestrus. Uteri were flushed for the recovery of conceptuses and the ipsilateral intercaruncular endometrium was sampled for gene expression analysis. Indoleamine 2,3-dioxygenase (IDO) mRNA, coding for the initial enzyme of the kynurenine pathway, was 18-fold (P < 0.001) more abundant in the endometrium of Day 18 pregnant v. non-pregnant animals. Tandem mass spectrometry revealed a decrease of endometrial l-tryptophan (P = 0.0008), but an increase of l-kynurenine concentration (P = 0.005) from Day 12 to Day 18, suggesting increasing IDO activity (P < 0.03). An in vitro coculture model of endometrial cells showed an induction of IDO expression following interferon-τ exposure primarily in stroma cells, which was confirmed by in situ hybridisation localising IDO mRNA mainly in deep stroma cells. Immunohistochemical analysis revealed fewer CD45-positive leucocytes in the zona basalis of pregnant animals. Elevated IDO activity may reduce the presence of leucocytes in the pregnant endometrium, providing a possible mechanism for protecting the semi-allogenic conceptus from maternal rejection.

  17. Early metabolic effects and mechanism of ammonium transport in yeast

    International Nuclear Information System (INIS)

    Pena, A.; Pardo, J.P.; Ramirez, J.

    1987-01-01

    Studies were performed to define the effects and mechanism of NH+4 transport in yeast. The following results were obtained. Glucose was a better facilitator than ethanol-H 2 O 2 for ammonium transport; low concentrations of uncouplers or respiratory inhibitors could inhibit the transport with ethanol as the substrate. With glucose, respiratory inhibitors showed only small inhibitory effects, and only high concentrations of azide or trifluoromethoxy carbonylcyanide phenylhydrazone could inhibit ammonium transport. Ammonium in the free state could be concentrated approximately 200-fold by the cells. Also, the addition of ammonium produced stimulation of both respiration and fermentation; an increased rate of H+ extrusion and an alkalinization of the interior of the cell; a decrease of the membrane potential, as monitored by fluorescent cyanine; an immediate decrease of the levels of ATP and an increase of ADP, which may account for the stimulation of both fermentation and respiration; and an increase of the levels of inorganic phosphate. Ammonium was found to inhibit 86Rb+ transport much less than K+. Also, while K+ produced a competitive type of inhibition, that produced by NH4+ was of the noncompetitive type. From the distribution ratio of ammonium and the pH gradient, an electrochemical potential gradient of around -180 mV was calculated. The results indicate that ammonium is transported in yeast by a mechanism similar to that of monovalent alkaline cations, driven by a membrane potential. The immediate metabolic effects of this cation seem to be due to an increased [H+]ATPase, to which its transport is coupled. However, the carriers seem to be different. The transport system studied in this work was that of low affinity

  18. Possible relationships between the early inflammatory response and subsequent fibrosis in rat skin after irradiation

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1975-01-01

    This study was designed to examine possible mechanistic relationships between the early inflammatory response and the subsequent fibrosis seen after radiation exposure. Anesthetized Rochester ex-Wistar rats were given single x-ray doses of either 2000 or 5000 rads to standardized fields of the inner thigh. The data suggest that two mechanisms are responsible for the radiation-induced increase in extravasation rate and vascular injury seen early after irradiation. First, direct cytocidal damage of the endothelium; and second, chemically mediated, possibly complement dependent mechanisms. Indirect histological evidence suggests a correlation between the PMN infiltrate and the indirect vascular damage. In addition, one may conclude from these data that (1) both direct and indirect damage to the vasculature play a role in influencing the subsequent late radiation-induced fibrosis; and (2) a decrease in the indirect damage may allow the maintenance of a supportive vasculature at lower doses or allow the reestablishment of a vascular bed in the case of higher doses

  19. Response to various periods of mechanical stimuli in Physarum plasmodium

    International Nuclear Information System (INIS)

    Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki

    2017-01-01

    Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli. (paper)

  20. The mechanical response of lithographically defined break junctions

    International Nuclear Information System (INIS)

    Huisman, E. H.; Bakker, F. L.; Wees, B. J. van; Trouwborst, M. L.; Molen, S. J. van der

    2011-01-01

    We present an experimental study on the mechanical response of lithographically defined break junctions by measuring atomic chain formation, tunneling traces and Gundlach oscillations. The calibration factor, i.e., the ratio between the electrode movement and the bending of the substrate, is found to be 2.5 times larger than expected from a simple mechanical model. This result is consistent with previous finite-element calculations. Comparing different samples, the mechanical response is found to be similar for electrode separations >4 A. However, for smaller electrode separations significant sample-to-sample variations appear. These variations are ascribed to differences in the shape of the two electrodes on the atomic scale which cannot be controlled by the fabrication process.

  1. Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

    Science.gov (United States)

    Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

    2017-08-01

    Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

  2. The prestress-dependent mechanical response of magnetorheological elastomers

    International Nuclear Information System (INIS)

    Feng, Jiabin; Xuan, Shouhu; Liu, Taixiang; Ge, Lin; Zhou, Hong; Gong, Xinglong; Yan, Lixun

    2015-01-01

    Magnetorheological elastomers (MREs) are intelligent materials consisting of a rubber matrix filled with magnetizable particles. In many engineering applications, MREs are usually pre-confined and work with constraint-induced prestress. The prestress can significantly change the mechanical properties of MREs. In this work, the influence of prestress on the mechanical response of MREs is studieds both experimentally and theoretically. The storage modulus as well as the magneto-induced modulus change non-linearly with increasing prestress and three regions can be found in the non-linear change. In the non-full contact region, the MREs present poor mechanical properties at small prestress due to the unevenness of the sample surface. In the full contact region, the MREs are under suitable prestress, thus they present good mechanical properties. In the overload region, the pre-configured microstructure of the MREs is destroyed under the large prestress. Moreover, an analytical model is proposed to study the prestress-dependent mechanical properties of MREs. It is revealed that the prestress can change the inter-particle distance, thus further affecting the mechanical response of MREs. (paper)

  3. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    Directory of Open Access Journals (Sweden)

    Ahmed R

    2014-03-01

    Full Text Available Rafay Ahmed,1 Matthew J Oborski,2 Misun Hwang,1 Frank S Lieberman,3 James M Mountz11Department of Radiology, 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Neurology and Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies

  4. Local mechanical stimulation induces components of the pathogen defense response in parsley

    Science.gov (United States)

    Gus-Mayer, Sabine; Naton, Beatrix; Hahlbrock, Klaus; Schmelzer, Elmon

    1998-01-01

    Cell suspension cultures of parsley (Petroselinum crispum) have previously been used as a suitable system for studies of the nonhost resistance response to Phytophthora sojae. In this study, we replaced the penetrating fungus by local mechanical stimulation by using a needle of the same diameter as a fungal hypha, by local application of a structurally defined fungus-derived elicitor, or by a combination of the two stimuli. Similar to the fungal infection hypha, the local mechanical stimulus alone induced the translocation of cytoplasm and nucleus to the site of stimulation, the generation of intracellular reactive oxygen intermediates (ROI), and the expression of some, but not all, elicitor-responsive genes. When the elicitor was applied locally to the cell surface without mechanical stimulation, intracellular ROI also accumulated rapidly, but morphological changes were not detected. A combination of the mechanical stimulus with simultaneous application of low doses of elicitor closely simulated early reactions to fungal infection, including cytoplasmic aggregation, nuclear migration, and ROI accumulation. By contrast, cytoplasmic rearrangements were impaired at high elicitor concentrations. Neither papilla formation nor hypersensitive cell death occurred under the conditions tested. These results suggest that mechanical stimulation by the invading fungus is responsible for the observed intracellular rearrangements and may trigger some of the previously demonstrated changes in the activity of elicitor-responsive genes, whereas chemical stimulation is required for additional biochemical processes. As yet unidentified signals may be involved in papilla formation and hypersensitive cell death. PMID:9653198

  5. Culturally Responsive Literacy Practices in an Early Childhood Community

    Science.gov (United States)

    Bennett, Susan V.; Gunn, AnnMarie Alberton; Gayle-Evans, Guda; Barrera, Estanislado S.; Leung, Cynthia B.

    2018-01-01

    Early childhood educators continue to see an increase in their culturally diverse student population. As our country continues to grow as a multicultural nation, it is imperative that our early childhood classrooms embrace this rich diversity and provide experiences that affirm all students, families and communities. We (teacher educators)…

  6. Response of mechanical properties of glasses to their chemical, thermal and mechanical histories

    DEFF Research Database (Denmark)

    Yue, Yuanzheng

    , surface, thermal history or excess entropy of the final glass state. Here I review recent progresses in understanding of the responses of mechanical properties of oxide glasses to the compositional variation, thermal history and mechanical deformation. The tensile strength, elastic modulus and hardness...... of glass fibers are dependent on the thermal history (measured as fictive temperature), tension, chemical composition and redox state. However, the fictive temperature affects the hardness of bulk glass in a complicated manner, i.e., the effect does not exhibit a clear regularity in the range...... and micro-cracks occurring during indentation of a glass is discussed briefly. Finally I describe the future perspectives and challenges in understanding responses of mechanical properties of oxide glasses to compositional variation, thermal history and mechanical deformation....

  7. Cell response to long term mechanical interaction with nanopipettes

    Science.gov (United States)

    Orynbayeva, Zulfiya; Singhal, Riju; Vitol, Elina; Bouchard, Michael; Azizkhan-Clifford, Jane; Layton, Bradley; Friedman, Gary; Gogotsi, Yury

    2009-03-01

    Traditional microinjection into cells is performed over a relatively short term. Pipettes are typically withdrawn following any kind of injection. On the other hand, there is growing interest in using nanopipettes for cellular and subcellular probing. This interest is partly due to new developments in nanopipette technology which employ carbon nanotubes and provide robustness, flexibility, and biocompatibility. However, as far as we know, no systematic study of physiological, biochemical, and biophysical processes associated with cell response to lengthy mechanical stimulations by nanopipette probing have been performed so far. We present a detailed investigation of a wide range of effects of long term pipette insertion into a cell. Both traditional glass micropipettes and the novel carbon nanotube-tipped probes were involved in this study. The mechanism of Ca2+ response to the mechanical stimuli introduced by the nanopipette, and the role of different organelles in this mechanism were studied. We hypothesize that the calcium response is a function of cytoskeleton integrity and the mode of coupling between the cytoskeleton and the plasma membrane domains.

  8. Molecular mechanisms of radioadaptive responses in human lymphoblastoid cells

    International Nuclear Information System (INIS)

    Kakimoto, Ayana; Taki, Keiko; Nakajima, Tetsuo

    2008-01-01

    Radioadaptive response is a biodefensive response observed in a variety of mammalian cells and animals where exposure to low dose radiation induces resistance against the subsequent high dose radiation. Elucidation of its mechanisms is important for risk estimation of low dose radiation because the radioadaptive response implies that low dose radiation affects cells/individuals in a different manner from high dose radiation. In the present study, we explored the molecular mechanisms of the radioadaptive response in human lymphoblastoid cells AHH-1 in terms of mutation at the hypoxanthine phosphoribosyltransferase (HPRT) gene locus. First we observed that preexposure to the priming dose in the range from 0.02 Gy to 0.2 Gy significantly reduced mutation frequency at HPRT gene locus after irradiation with 3 Gy of X rays. As no significant adaptive response was observed with the priming dose of 0.005 Gy, it was indicated that the lower limit of the priming dose to induce radioadaptive response may be between 0.005 Gy and 0.02 Gy. Second, we examined the effect of 3-amino-benzamide (3AB), an inhibitor of poly(ADP-ribose)polymerase1, which has been reported to inhibit the radioadaptive response in terms of chromosome aberration. However we could observe significant radioadaptive responses in terms of mutation even in the presence of 3AB. These findings suggested that molecular mechanisms of the radioadaptive response in terms of mutation may be different from that for radioadaptive responses in terms of chromosomal aberration, although we could not exclude a possibility that the differential effects of 3AB was due to cell type difference. Finally, by performing a comprehensive analysis of alterations in gene expression using high coverage expression profiling (HiCEP), we could identify 17 genes whose expressions were significantly altered 6 h after irradiation with 0.02 Gy. We also found 17 and 20 genes, the expressions of which were different with or without priming

  9. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

    Directory of Open Access Journals (Sweden)

    Tetu Bernard

    2008-02-01

    Full Text Available Abstract Background Chemotherapy (CT resistance in ovarian cancer (OC is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155, following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism, signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes, cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular

  10. Item response theory analysis of the mechanics baseline test

    Science.gov (United States)

    Cardamone, Caroline N.; Abbott, Jonathan E.; Rayyan, Saif; Seaton, Daniel T.; Pawl, Andrew; Pritchard, David E.

    2012-02-01

    Item response theory is useful in both the development and evaluation of assessments and in computing standardized measures of student performance. In item response theory, individual parameters (difficulty, discrimination) for each item or question are fit by item response models. These parameters provide a means for evaluating a test and offer a better measure of student skill than a raw test score, because each skill calculation considers not only the number of questions answered correctly, but the individual properties of all questions answered. Here, we present the results from an analysis of the Mechanics Baseline Test given at MIT during 2005-2010. Using the item parameters, we identify questions on the Mechanics Baseline Test that are not effective in discriminating between MIT students of different abilities. We show that a limited subset of the highest quality questions on the Mechanics Baseline Test returns accurate measures of student skill. We compare student skills as determined by item response theory to the more traditional measurement of the raw score and show that a comparable measure of learning gain can be computed.

  11. Passive and active response of bacteria under mechanical compression

    Science.gov (United States)

    Garces, Renata; Miller, Samantha; Schmidt, Christoph F.; Byophysics Team; Institute of Medical Sciences Collaboration

    Bacteria display simple but fascinating cellular structures and geometries. Their shapes are the result of the interplay between osmotic pressure and cell wall construction. Typically, bacteria maintain a high difference of osmotic pressure (on the order of 1 atm) to the environment. This pressure difference (turgor pressure) is supported by the cell envelope, a composite of lipid membranes and a rigid cell wall. The response of the cell envelope to mechanical perturbations such as geometrical confinements is important for the cells survival. Another key property of bacteria is the ability to regulate turgor pressure after abrupt changes of external osmotic conditions. This response relies on the activity of mechanosensitive (MS) channels: membrane proteins that release solutes in response to excessive stress in the cell envelope. We here present experimental data on the mechanical response of the cell envelope and on turgor regulation of bacteria subjected to compressive forces. We indent living cells with micron-sized beads attached to the cantilever of an atomic force microscope (AFM). This approach ensures global deformation of the cell. We show that such mechanical loading is sufficient to gate mechanosensitive channels in isosmotic conditions.

  12. Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

    Science.gov (United States)

    Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

    2018-01-01

    There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

  13. Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

    Science.gov (United States)

    Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

    2017-05-25

    -treatment and FU-5P (-.23 ≤ r ≤ .23). Due to several limitations (e.g., small sample size, lack of a control group) the results of this study have to be interpreted cautiously. Our findings show that reliable changes in regard to affective-cognitive and behavioral variables can take place very early in CBT of patients with distressing MUS. These early changes seem to be predictive of the outcome at therapy termination. Future studies are needed in order to replicate our results, and to identify mechanisms of these early response patterns in somatoform patients. ISRCTN. ISRCTN17188363 . Registered retrospectively on 29 March 2007.

  14. Early life stress interactions with the epigenome: potential mechanisms driving vulnerability towards psychiatric illness

    Science.gov (United States)

    Olive, Michael Foster

    2014-01-01

    Throughout the 20th century a body of literature concerning the long lasting effects of early environment was produced. Adverse experiences in early life, or early life stress (ELS), is associated with a higher risk for developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions. PMID:25003947

  15. Early-life stress interactions with the epigenome: potential mechanisms driving vulnerability toward psychiatric illness.

    Science.gov (United States)

    Lewis, Candace R; Olive, M Foster

    2014-09-01

    Throughout the 20th century a body of literature concerning the long-lasting effects of the early environment was produced. Adverse experiences in early life, or early-life stress (ELS), is associated with a higher risk of developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far-reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS-induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions.

  16. Mechanisms of the placebo response in pain in osteoarthritis.

    Science.gov (United States)

    Abhishek, A; Doherty, M

    2013-09-01

    Administration of a placebo associates with symptomatic improvement in many conditions--the so-called placebo response. In this review we explain the concept of placebo response, examine the data that supports existence in osteoarthritis (OA), and discuss its possible mechanisms and determinants. A Pubmed literature search was carried out. Key articles were identified, and their findings discussed in a narrative review. Pain, stiffness, self-reported function and physician-global assessment in OA clearly improve in response to placebo. However, more objective measures such as quadriceps strength and radiographic progression appear less responsive. Although not directly studied in OA, contextual effects, patient expectation and conditioning are believed to be the main mechanisms. Neurotransmitter changes that mediate placebo-induced analgesia include increased endogenous opioid levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost all parts of the brain involved in pain processing are influenced during placebo-induced analgesia. Determinants of the magnitude of placebo response include the patient-practitioner interaction, treatment response expectancy, knowledge of being treated, patient personality traits and placebo specific factors such as the route and frequency of administration, branding, and treatment costs. Clearer understanding of the neurobiology of placebo response validates its existence as a real phenomenon. Although routine administration of placebo for symptomatic improvement is difficult to justify, contextual factors that enhance treatment response should be employed in the management of chronic painful conditions such as OA where available treatments have only modest efficacy. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  17. Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise.

    Science.gov (United States)

    D'Lugos, Andrew C; Patel, Shivam H; Ormsby, Jordan C; Curtis, Donald P; Fry, Christopher S; Carroll, Chad C; Dickinson, Jared M

    2018-04-01

    Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation. Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the cellular mechanisms regulating the adaptive response of skeletal muscle. The purpose of this study was to determine whether prior consumption of the COX inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in human skeletal muscle after RE. In a double-blinded, randomized, crossover design, healthy young men ( n = 8, 25 ± 1 yr) performed two trials of unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin (mTOR) complex 1 signaling was assessed through immunoblot and immunohistochemistry, and mRNA expression of myogenic genes was examined via RT-qPCR. At 1 h p-rpS6 Ser240/244 was increased in both groups but to a greater extent in PLA. At 3 h p-S6K1 Thr389 was elevated only in PLA. Furthermore, localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to alter the early adaptive cellular response of skeletal muscle to RE. These findings further highlight the mechanisms through which COX-inhibiting drugs impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The extent to which the cellular reaction to acetaminophen impacts the mechanisms regulating the adaptive response of human skeletal muscle to resistance exercise is not well understood. Consumption of acetaminophen before

  18. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    OpenAIRE

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initia...

  19. Phenomena of synchronized response in biosystems and the possible mechanism.

    Science.gov (United States)

    Xu, Jingjing; Yang, Fan; Han, Danhong; Xu, Shengyong

    2018-02-05

    Phenomena of synchronized response is common among organs, tissues and cells in biosystems. We have analyzed and discussed three examples of synchronization in biosystems, including the direction-changing movement of paramecia, the prey behavior of flytraps, and the simultaneous discharge of electric eels. These phenomena and discussions support an electrical communication mechanism that in biosystems, the electrical signals are mainly soliton-like electromagnetic pulses, which are generated by the transient transmembrane ionic current through the ion channels and propagate along the dielectric membrane-based softmaterial waveguide network to complete synchronized responses. This transmission model implies that a uniform electrical communication mechanism might have been naturally developed in biosystem. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Early change in coping strategies in responsive treatments for borderline personality disorder: A mediation analysis.

    Science.gov (United States)

    Kramer, Ueli; Keller, Sabine; Caspar, Franz; de Roten, Yves; Despland, Jean-Nicolas; Kolly, Stéphane

    2017-05-01

    Difficulty in emotion regulation is a hallmark feature of patients with borderline personality disorder (BPD). Therefore, change in the frequency of certain patients' coping strategies-aiming at emotion regulation-are among the most promising mechanisms of change in treatments for BPD. In parallel, it was highlighted that therapist responsiveness significantly contributed to outcome across treatment approaches (Stiles, 2009). Based on a randomized controlled trial (Kramer et al., 2014), the present process-outcome mediation analysis aims at examining the patient's early change in frequency of coping strategies-in particular the decrease in behavioral forms of coping-as potential mechanism of change in responsive treatments for BPD. A total of 57 patients with BPD were included in the present analysis, out of whom 27 were randomly assigned to a 10-session psychiatric treatment and 30 to a 10-session psychiatric treatment augmented with the responsive intervention of the motive-oriented therapeutic relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et al., 2005; 171 sessions analyzed in total), a validated observer-rated method for assessing coping strategies in the therapy process. Psychological distress was assessed using the OQ-45 at intake, after Session 5, and after Session 10. The results confirmed a responsiveness effect associated with the motive-oriented therapeutic relationship and showed a significant decrease in frequency of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not different between the 2 conditions. In addition, we demonstrated that the early decrease in behavioral forms of coping between Sessions 1 and 5 partially mediated the link between the group assignment and the change in psychological distress between Sessions 5 and 10. These results shed light on the centrality of therapist responsiveness in treatments for

  1. Responsive feeding: establishing healthy eating behaviour early on ...

    African Journals Online (AJOL)

    2013-04-12

    Apr 12, 2013 ... facilitation of self-regulation skills early in life may predict future food intake ... eating behaviour through communicating their attitudes and beliefs about ..... as well as disturbances in self-esteem, body image and socialisation ...

  2. The Venturia Apple Pathosystem: Pathogenicity Mechanisms and Plant Defense Responses

    Directory of Open Access Journals (Sweden)

    Gopaljee Jha

    2009-01-01

    Full Text Available Venturia inaequalis is the causal agent of apple scab, a devastating disease of apple. We outline several unique features of this pathogen which are useful for molecular genetics studies intended to understand plant-pathogen interactions. The pathogenicity mechanisms of the pathogen and overview of apple defense responses, monogenic and polygenic resistance, and their utilization in scab resistance breeding programs are also reviewed.

  3. Mechanical response tissue analyzer for estimating bone strength

    Science.gov (United States)

    Arnaud, Sara B.; Steele, Charles; Mauriello, Anthony

    1991-01-01

    One of the major concerns for extended space flight is weakness of the long bones of the legs, composed primarily of cortical bone, that functions to provide mechanical support. The strength of cortical bone is due to its complex structure, described simplistically as cylinders of parallel osteons composed of layers of mineralized collagen. The reduced mechanical stresses during space flight or immobilization of bone on Earth reduces the mineral content, and changes the components of its matrix and structure so that its strength is reduced. Currently, the established clinical measures of bone strength are indirect. The measures are based on determinations of mineral density by means of radiography, photon absorptiometry, and quantitative computer tomography. While the mineral content of bone is essential to its strength, there is growing awareness of the limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially limitations of the measurement as the sole predictor of fracture risk in metabolic bone diseases, especially osteoporosis. Other experimental methods in clinical trials that more directly evaluate the physical properties of bone, and do not require exposure to radiation, include ultrasound, acoustic emission, and low-frequency mechanical vibration. The last method can be considered a direct measure of the functional capacity of a long bone since it quantifies the mechanical response to a stimulus delivered directly to the bone. A low frequency vibration induces a response (impedance) curve with a minimum at the resonant frequency, that a few investigators use for the evaluation of the bone. An alternative approach, the method under consideration, is to use the response curve as the basis for determination of the bone bending stiffness EI (E is the intrinsic material property and I is the cross-sectional moment of inertia) and mass, fundamental mechanical properties of bone.

  4. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    Science.gov (United States)

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  5. Impacts of triclosan exposure on zebrafish early-life stage: Toxicity and acclimation mechanisms.

    Science.gov (United States)

    Falisse, Elodie; Voisin, Anne-Sophie; Silvestre, Frédéric

    2017-08-01

    Triclosan (TCS) is a broad spectrum antibacterial agent widely used in personal care products and present in most aquatic ecosystems. This study investigated the occurrence of triclosan acclimation and the biological mechanisms underlying the stress response triggered in early-life stage of zebrafish. Zebrafish eggs were first exposed to four different sublethal concentrations of TCS (2, 20, 50 and 100μg/L) for 7days following fertilization and subsequently exposed to a lethal concentration of TCS (1000μg/L). During the time-to-death exposure (TTD), mortality was continuously recorded to evaluate if increased resistance occurred. Overall, larvae exposed to 50μg/L of TCS demonstrated higher sensitivity, with delayed hatching and increased mortality during the sub-lethal exposure and significant lower mean time-to-death (TTD) value compared to the other groups. Interestingly, fish exposed to the highest concentration of TCS (100μg/L) presented a similar mean TTD value as controls and a significantly better survival in comparison with embryos exposed to 50μg/L, suggesting that acclimation process has been triggered at this concentration. Proteomic and enzymatic analyses were conducted on 7days post fertilization (dpf) larvae exposed to 50μg/L and 100μg/L of TCS giving insights into the functional changes triggered at those specific concentrations. TCS seemed to affect proteins involved in cytoskeleton, stress response, eyes and neuronal development. This was endorsed by the enzymatic results, which suggest impairment in glutathione metabolism and acute neurotoxicity. A significant 2.5-fold and 3-fold increase of AChE activity was observed following TCS exposure. Moreover, GPx activity was significantly increased whereas a significant inhibition of GR activity was observed, suggesting that de novo synthesis of reduced GSH might occur in order to maintain the ratio between reduced and oxidized GSH. Proteomic results revealed possible candidate protein involved in

  6. Thermodynamical aspects of modeling the mechanical response of granular materials

    International Nuclear Information System (INIS)

    Elata, D.

    1995-01-01

    In many applications in rock physics, the material is treated as a continuum. By supplementing the related conservation laws with constitutive equations such as stress-strain relations, a well-posed problem can be formulated and solved. The stress-strain relations may be based on a combination of experimental data and a phenomenological or micromechanical model. If the model is physically sound and its parameters have a physical meaning, it can serve to predict the stress response of the material to unmeasured deformations, predict the stress response of other materials, and perhaps predict other categories of the mechanical response such as failure, permeability, and conductivity. However, it is essential that the model be consistent with all conservation laws and consistent with the second law of thermodynamics. Specifically, some models of the mechanical response of granular materials proposed in literature, are based on intergranular contact force-displacement laws that violate the second law of thermodynamics by permitting energy generation at no cost. This diminishes the usefulness of these models as it invalidates their predictive capabilities. [This work was performed under the auspices of the U.S. DOE by Lawrence Livermore National Laboratory under Contract No. W-7405-ENG-48.

  7. Mechanical response of wall-patterned GaAs surface

    International Nuclear Information System (INIS)

    Le Bourhis, E.; Patriarche, G.

    2005-01-01

    Wall-patterned GaAs surfaces have been elaborated by photolithography and dry etching. Different surfaces were produced in order to change the aspect ratio of the walls formed at the substrate surface. The mechanical behaviour of individual walls was investigated by nanoindentation and the responses were compared to that of a standard bulk reference (flat surface). Deviation from the bulk response is detected in a load range of 1-25 mN depending on the aspect ratio of the walls. A central plastic zone criterion is proposed in view of transmission electron microscopy images of indented walls and allows the prediction of the response deviation of a given wall if its width is known. The mechanical response of the different types of walls is further investigated in terms of stiffness, total penetration of indenter and apparent hardness, and is scanned in relation to the proximity of a wall side. Overall results show that contact stiffness remains almost unaffected by aspect ratio, while penetration drastically increases because of the free sides of the wall as compared to a flat surface (bulk substrate). The application of substrate patterning for optoelectronic devices is discussed in the perspective of eliminating residual dislocations appearing in mismatched structures

  8. Mechanisms regulating osteoblast response to surface microtopography and vitamin D

    Science.gov (United States)

    Bell, Bryan Frederick, Jr.

    A comprehensive understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is essential in the design of advanced biomaterials that better promote bone growth and osseointegration of implants. Dental implants with roughened surfaces and high surface energy are well known to promote osteoblast differentiation in vitro and promote increased bone-to-implant contact in vivo. In addition, increased surface roughness increases osteoblasts response to the vitamin D metabolite 1alpha,25(OH)2D3. However, the exact mechanisms mediating cell response to surface properties and 1alpha,25(OH)2D3 are still being elucidated. The central aim of the thesis is to investigate whether integrin signaling in response to rough surface microtopography enhances osteoblast differentiation and responsiveness to 1alpha,25(OH)2D3. The hypothesis is that the integrin alpha5beta1 plays a role in osteoblast response to surface microtopography and that 1alpha,25(OH) 2D3 acts through VDR-independent pathways involving caveolae to synergistically enhance osteoblast response to surface roughness and 1alpha,25(OH) 2D3. To test this hypothesis the objectives of the studies performed in this thesis were: (1) to determine if alpha5beta 1 signaling is required for osteoblast response to surface microstructure; (2) to determine if increased responsiveness to 1alpha,25(OH)2D 3 requires the vitamin D receptor, (3) to determine if rough titanium surfaces functionalized with the peptides targeting integrins (RGD) and transmembrane proteoglycans (KRSR) will enhance both osteoblast proliferation and differentiation, and (4) to determine whether caveolae, which are associated with integrin and 1alpha,25(OH)2D3 signaling, are required for enhance osteogenic response to surface microstructure and 1alpha,25(OH)2D 3. The results demonstrate that integrins, VDR, and caveolae play important roles in mediating osteoblast response to surface properties and 1alpha,25

  9. Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

    International Nuclear Information System (INIS)

    Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

    2002-01-01

    Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

  10. Mechanics of responsive polymers via conformationally switchable molecules

    Science.gov (United States)

    Brighenti, Roberto; Artoni, Federico; Vernerey, Franck; Torelli, Martina; Pedrini, Alessandro; Domenichelli, Ilaria; Dalcanale, Enrico

    2018-04-01

    Active materials are those capable of giving some physical reaction under external stimuli coming from the environment such as temperature, pH, light, mechanical stress, etc. Reactive polymeric materials can be obtained through the introduction of switchable molecules in their network, i.e. molecules having two distinct stable conformations: if properly linked to the hosting polymer chains, the switching from one state to the other can promote a mechanical reaction of the material, detectable at the macroscale, and thus enables us to tune the response according to a desired functionality. In the present paper, the main aspects of the mechanical behavior of polymeric materials with embedded switchable molecules-properly linked to the polymer's chains-are presented and discussed. Starting from the micro mechanisms occurring in such active material, a continuum model is developed, providing a straightforward implementation in computational approaches. Finally, some experimental outcomes related to a switchable molecules (known as quinoxaline cavitands) added to an elastomeric PDMS under chemical stimuli, are presented and quantitatively discussed through the use of the developed mechanical framework.

  11. Early capillary flux homogenization in response to neural activation.

    Science.gov (United States)

    Lee, Jonghwan; Wu, Weicheng; Boas, David A

    2016-02-01

    This Brief Communication reports early homogenization of capillary network flow during somatosensory activation in the rat cerebral cortex. We used optical coherence tomography and statistical intensity variation analysis for tracing changes in the red blood cell flux over hundreds of capillaries nearly at the same time with 1-s resolution. We observed that while the mean capillary flux exhibited a typical increase during activation, the standard deviation of the capillary flux exhibited an early decrease that happened before the mean flux increase. This network-level data is consistent with the theoretical hypothesis that capillary flow homogenizes during activation to improve oxygen delivery. © The Author(s) 2015.

  12. Discrimination of timbre in early auditory responses of the human brain.

    Directory of Open Access Journals (Sweden)

    Jaeho Seol

    Full Text Available BACKGROUND: The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1-testing (S2 paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2 for both same and different conditions in the both hemispheres. CONCLUSIONS/SIGNIFICANCES: Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

  13. Study on the early warning mechanism for the security of blast furnace hearths

    Science.gov (United States)

    Zhao, Hong-bo; Huo, Shou-feng; Cheng, Shu-sen

    2013-04-01

    The campaign life of blast furnace (BF) hearths has become the limiting factor for safety and high efficiency production of modern BFs. However, the early warning mechanism of hearth security has not been clear. In this article, based on heat transfer calculations, heat flux and erosion monitoring, the features of heat flux and erosion were analyzed and compared among different types of hearths. The primary detecting elements, mathematical models, evaluating standards, and warning methods were discussed. A novel early warning mechanism with the three-level quantificational standards was proposed for BF hearth security.

  14. Early tracheostomy in severe traumatic brain injury: evidence for decreased mechanical ventilation and increased hospital mortality

    Science.gov (United States)

    Dunham, C Michael; Cutrona, Anthony F; Gruber, Brian S; Calderon, Javier E; Ransom, Kenneth J; Flowers, Laurie L

    2014-01-01

    tracheostomy (OR 1.97; p tracheostomy. Further, this study implies that mechanical ventilation is reduced with early tracheostomy. Both the randomized trial and retrospective meta-analysis indicate that risk for hospital death increases with early tracheostomy. Findings imply that early tracheostomy for severe brain injury is not a prudent routine policy. PMID:24624310

  15. Elevated Amygdala Response to Faces following Early Deprivation

    Science.gov (United States)

    Tottenham, N.; Hare, T. A.; Millner, A.; Gilhooly, T.; Zevin, J. D.; Casey, B. J.

    2011-01-01

    A functional neuroimaging study examined the long-term neural correlates of early adverse rearing conditions in humans as they relate to socio-emotional development. Previously institutionalized (PI) children and a same-aged comparison group were scanned using functional magnetic resonance imaging (fMRI) while performing an Emotional Face Go/Nogo…

  16. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

    Directory of Open Access Journals (Sweden)

    Jody Groenendyk

    Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

  17. Response mechanisms of attached premixed flames subjected to harmonic forcing

    Science.gov (United States)

    Shreekrishna

    vicinity of typical screech frequencies in gas turbine combustors. The nonlinear response problem is exclusively studied in the case of equivalence ratio coupling. Various nonlinearity mechanisms are identified, amongst which the crossover mechanisms, viz., stoichiometric and flammability crossovers, are seen to be responsible in causing saturation in the overall heat release magnitude of the flame. The response physics remain the same across various preheat temperatures and reactant pressures. Finally, comparisons between the chemiluminescence transfer function obtained experimentally and the heat release transfer functions obtained from the reduced order model (ROM) are performed for lean, CH4/Air swirl-stabilized, axisymmetric V-flames. While the comparison between the phases of the experimental and theoretical transfer functions are encouraging, their magnitudes show disagreement at lower Strouhal number gains show disagreement.

  18. FAMREC, PWR Lateral Mechanical Fuel Rod Assembly Response

    International Nuclear Information System (INIS)

    Guenzler, R.C.

    1995-01-01

    1 - Description of program or function: The Fuel Assembly Mechanical Response Code (FAMREC) calculates the lateral mechanical response of a row of fuel assemblies while allowing for two types of nonlinearities. The first type is a geometric nonlinearity in the form of gaps between individual assemblies and between peripheral assemblies and a boundary wall. Impacting is monitored across the gaps. The second nonlinearity is the permanent deformation of the fuel assembly spacer grid to compressive loading. 2 - Method of solution: The response is calculated in the modal plane. The coupled differential equations are solved in closed form using Laplace transformations. The discrete displacements and velocities are then calculated and the gaps in the system monitored at each axial elevation for impacting. These impact forces are then applied statistically at a given time-step, and equilibrium is found using a Gaussian elimination technique. Three impact force calculation methods are available: 1- a linear impact force and crushing load audit calculation, 2- a more detailed linear impact force and crushing load calculation, and 3- a non-linear grid calculation which allows for plastic deformation of the fuel assembly spacer grids. 3 - Restrictions on the complexity of the problem: Maxima of: 3601 time-steps and forces; 80 modes; 30 applied forces; 15 fuel assemblies; and 5 impact grids per assembly

  19. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    Science.gov (United States)

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  20. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  1. Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

    Science.gov (United States)

    Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

    2015-09-01

    Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry. © 2015 Poultry Science Association Inc.

  2. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas

    2013-01-01

    ) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13......BACKGROUND: Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients...... treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17...

  3. Model-based flaw localization from perturbations in the dynamic response of complex mechanical structures

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, D H

    2009-02-24

    A new method of locating structural damage using measured differences in vibrational response and a numerical model of the undamaged structure has been presented. This method is particularly suited for complex structures with little or no symmetry. In a prior study the method successively located simulated damage from measurements of the vibrational response on two simple structures. Here we demonstrate that it can locate simulated damage in a complex structure. A numerical model of a complex structure was used to calculate the structural response before and after the introduction of a void. The method can now be considered for application to structures of programmatic interest. It could be used to monitor the structural integrity of complex mechanical structures and assemblies over their lifetimes. This would allow early detection of damage, when repair is relatively easy and inexpensive. It would also allow one to schedule maintenance based on actual damage instead of a time schedule.

  4. The evolution of cognitive mechanisms in response to cultural innovations.

    Science.gov (United States)

    Lotem, Arnon; Halpern, Joseph Y; Edelman, Shimon; Kolodny, Oren

    2017-07-24

    When humans and other animals make cultural innovations, they also change their environment, thereby imposing new selective pressures that can modify their biological traits. For example, there is evidence that dairy farming by humans favored alleles for adult lactose tolerance. Similarly, the invention of cooking possibly affected the evolution of jaw and tooth morphology. However, when it comes to cognitive traits and learning mechanisms, it is much more difficult to determine whether and how their evolution was affected by culture or by their use in cultural transmission. Here we argue that, excluding very recent cultural innovations, the assumption that culture shaped the evolution of cognition is both more parsimonious and more productive than assuming the opposite. In considering how culture shapes cognition, we suggest that a process-level model of cognitive evolution is necessary and offer such a model. The model employs relatively simple coevolving mechanisms of learning and data acquisition that jointly construct a complex network of a type previously shown to be capable of supporting a range of cognitive abilities. The evolution of cognition, and thus the effect of culture on cognitive evolution, is captured through small modifications of these coevolving learning and data-acquisition mechanisms, whose coordinated action is critical for building an effective network. We use the model to show how these mechanisms are likely to evolve in response to cultural phenomena, such as language and tool-making, which are associated with major changes in data patterns and with new computational and statistical challenges.

  5. Mechanical response of human female breast skin under uniaxial stretching.

    Science.gov (United States)

    Kumaraswamy, N; Khatam, Hamed; Reece, Gregory P; Fingeret, Michelle C; Markey, Mia K; Ravi-Chandar, Krishnaswamy

    2017-10-01

    Skin is a complex material covering the entire surface of the human body. Studying the mechanical properties of skin to calibrate a constitutive model is of great importance to many applications such as plastic or cosmetic surgery and treatment of skin-based diseases like decubitus ulcers. The main objective of the present study was to identify and calibrate an appropriate material constitutive model for skin and establish certain universal properties that are independent of patient-specific variability. We performed uniaxial tests performed on breast skin specimens freshly harvested during mastectomy. Two different constitutive models - one phenomenological and another microstructurally inspired - were used to interpret the mechanical responses observed in the experiments. Remarkably, we found that the model parameters that characterize dependence on previous maximum stretch (or preconditioning) exhibited specimen-independent universal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The response of an individual vortex to local mechanical contact

    Science.gov (United States)

    Kremen, Anna; Wissberg, Shai; Shperber, Yishai; Kalisky, Beena

    2016-05-01

    Recently we reported a new way to manipulate vortices in thin superconducting films by local mechanical contact without magnetic field, current or altering the pinning landscape [1]. We use scanning superconducting interference device (SQUID) microscopy to image the vortices, and a piezo element to push the tip of a silicon chip into contact with the sample. As a result of the stress applied at the contact point, vortices in the proximity of the contact point change their location. Here we study the characteristics of this vortex manipulation, by following the response of individual vortices to single contact events. Mechanical manipulation of vortices provides local view of the interaction between strain and nanomagnetic objects, as well as controllable, effective, localized, and reproducible manipulation technique.

  7. Microtubules self-repair in response to mechanical stress

    Science.gov (United States)

    Schaedel, Laura; John, Karin; Gaillard, Jérémie; Nachury, Maxence V.; Blanchoin, Laurent; Théry, Manuel

    2015-11-01

    Microtubules--which define the shape of axons, cilia and flagella, and provide tracks for intracellular transport--can be highly bent by intracellular forces, and microtubule structure and stiffness are thought to be affected by physical constraints. Yet how microtubules tolerate the vast forces exerted on them remains unknown. Here, by using a microfluidic device, we show that microtubule stiffness decreases incrementally with each cycle of bending and release. Similar to other cases of material fatigue, the concentration of mechanical stresses on pre-existing defects in the microtubule lattice is responsible for the generation of more extensive damage, which further decreases microtubule stiffness. Strikingly, damaged microtubules were able to incorporate new tubulin dimers into their lattice and recover their initial stiffness. Our findings demonstrate that microtubules are ductile materials with self-healing properties, that their dynamics does not exclusively occur at their ends, and that their lattice plasticity enables the microtubules' adaptation to mechanical stresses.

  8. How does a neuron know to modulate its epigenetic machinery in response to early-life environment/experience?

    Directory of Open Access Journals (Sweden)

    Carley A Karsten

    2013-08-01

    Full Text Available Exciting information is emerging about epigenetic mechanisms and their role in long-lasting changes of neuronal gene expression. Whereas these mechanisms are active throughout life, recent findings point to a critical window of early postnatal development during which neuronal gene expression may be persistently re-programmed via epigenetic modifications. However, it remains unclear how the epigenetic machinery is modulated. Here we focus on an important example of early-life programming: the effect of sensory input from the mother on expression patterns of key stress-related genes in the developing brain. We focus on the lasting effects of this early life experience on corticotropin releasing hormone (CRH gene expression in the hypothalamus, and describe recent work that integrates organism-wide signals with cellular signals that in turn impact epigenetic regulation. We describe the operational brain networks that convey sensory input to CRH-expressing cells, and highlight the resulting re-wiring of synaptic connectivity to these neurons. We then move from intercellular to intracellular mechanisms, speculating about the induction and maintenance of lifelong CRH repression provoked by early-life experience. Elucidating such pathways is critical for understanding the enduring links between experience and gene expression. In the context of responses to stress, such mechanisms should contribute to vulnerability or resilience to post-traumatic stress disorder (PTSD and other stress-related disorders.

  9. Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

    Science.gov (United States)

    Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

    2015-12-01

    Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

  10. Evaluation of the sheet mechanical response to laser welding processes

    International Nuclear Information System (INIS)

    Carmignani, B.; Daneri, A.; Toselli, G.; Bellei, M.

    1995-07-01

    The simulation of the mechanical response of steel sheets, due to the heating during welding processes by a laser source beam, obtained by Abaqus standard code, is discussed. Different hypotheses for the material behaviour at temperatures greater than the fusion one have been tested and compared; in particular, some tests have been made taking the annealing effect into account by means of an user routine UMAT developed ad hoc. This work was presented at the 8th international Abaqus Users' conference at Paris, 31 May - 2 June 1995

  11. Neural responses to macronutrients: hedonic and homeostatic mechanisms.

    Science.gov (United States)

    Tulloch, Alastair J; Murray, Susan; Vaicekonyte, Regina; Avena, Nicole M

    2015-05-01

    The brain responds to macronutrients via intricate mechanisms. We review how the brain's neural systems implicated in homeostatic control of feeding and hedonic responses are influenced by the ingestion of specific types of food. We discuss how these neural systems are dysregulated in preclinical models of obesity. Findings from these studies can increase our understanding of overeating and, perhaps in some cases, the development of obesity. In addition, a greater understanding of the neural circuits affected by the consumption of specific macronutrients, and by obesity, might lead to new treatments and strategies for preventing unhealthy weight gain. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. Earthquake responses of a beam supported by a mechanical snubber

    International Nuclear Information System (INIS)

    Ohmata, Kenichiro; Ishizu, Seiji.

    1989-01-01

    The mechanical snubber is an earthquakeproof device for piping systems under particular circumstances such as high temperature and radioactivity. It has nonlinearities in both load and frequency response. In this report, the resisting force characteristics of the snubber and earthquake responses of piping (a simply supported beam) which is supported by the snubber are simulated using Continuous System Simulation Language (CSSL). Digital simulations are carried out for various kinds of physical properties of the snubber. The restraint effect and the maximum resisting force of the snubber during earthquakes are discussed and compared with the case of an oil damper. The earthquake waves used here are E1 Centro N-S and Akita Harbour N-S (Nihonkai-Chubu earthquake). (author)

  13. Escape response of planktonic protists to fluid mechanical signals

    DEFF Research Database (Denmark)

    Jakobsen, Hans Henrik

    2001-01-01

    The escape response to fluid mechanical signals was examined in 6 protists, 4 ciliates and 2 dinoflagellates. When exposed to a siphon flow. 3 species of ciliates, Balanion comatum, Strobilidium sp., and Mesodinium pulex, responded with escape jumps. The threshold deformation rates required...... times lower than that of a non-jumping similar sized protist when the predator was Temora longicornis, which captures prey entrained in a feeding current. However, when the predator was the ambush- feeding copepod Acartia tonsa, the predation mortalities of jumping and non-jumping protists were...... of similar magnitude. Escape responses may thus be advantageous in some situations. However, jumping behaviour may also enhance susceptibility to some predators, explaining the different predator avoidance strategies (jumping or not) that have evolved in planktonic protists....

  14. DNA Methylation: A Mechanism for Embedding Early Life Experiences in the Genome

    Science.gov (United States)

    Szyf, Moshe; Bick, Johanna

    2013-01-01

    Although epidemiological data provide evidence that early life experience plays a critical role in human development, the mechanism of how this works remains in question. Recent data from human and animal literature suggest that epigenetic changes, such as DNA methylation, are involved not only in cellular differentiation but also in the…

  15. Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

    DEFF Research Database (Denmark)

    Frederiksen, B; Specht, L; Henrichsen, J

    1989-01-01

    response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response....

  16. Orthostatic function and the cardiovascular response to early mobilization after breast cancer surgery

    DEFF Research Database (Denmark)

    Gamborg Müller, Rasmus; Bundgaard-Nielsen, Morten; Kehlet, H

    2010-01-01

    procedures, because of an attenuated cardiovascular response, but the cardiovascular response and the incidence of orthostatic intolerance after minor procedures have not been clarified. We investigated the cardiovascular response and the incidence of orthostatic intolerance during early mobilization after...... breast cancer surgery....

  17. Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System

    NARCIS (Netherlands)

    Douw, G.; Huisman-de Waal, G.J.; Zanten, A.R. van; Hoeven, J.G. van der; Schoonhoven, L.

    2017-01-01

    AIMS AND OBJECTIVES: To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning

  18. Bone density does not reflect mechanical properties in early-stage arthrosis

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, CC; Hvid, I

    2001-01-01

    : medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure...... cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests...

  19. Outcome of poor response paediatric AML using early SCT.

    Science.gov (United States)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas; Forestier, Erik; Gustafsson, Britt; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Hasle, Henrik

    2013-03-01

    Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients treated with SCT. Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13, matched sibling donors in 6, cord blood donor in 4, and haploidentical donor in two. The median follow-up for the 31 poor responding patients was 2.6 years (range 0.4 - 8.1 years) and 3-year probability of survival 70% (95% CI 59-77%). The poor responders in the NOPHO-AML 2004 protocol had a favourable prognosis treated with time-intensive induction followed by SCT. © 2012 John Wiley & Sons A/S.

  20. Hypertensive response to exercise: mechanisms and clinical implication.

    Science.gov (United States)

    Kim, Darae; Ha, Jong-Won

    2016-01-01

    A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates that a HRE is associated with functional and structural abnormalities of left ventricle, especially when accompanied by increased central blood pressure. A HRE harbors prognostic significance in future development of hypertension and increased cardiovascular events, particularly if a HRE is documented in moderate intensity of exercise. As supported by previous studies, a HRE is not a benign phenomenon, however, currently, whether to treat a HRE is controversial with uncertain treatment strategy. Considering underlying mechanisms, angiotensin receptor blockers and beta blockers can be suggested in individuals with HRE, however, evidences for efficacy and outcomes of treatment of HRE in individuals without hypertension is scarce and therefore warrants further studies.

  1. Papillary Ductal Plugging is a Mechanism for Early Stone Retention in Brushite Stone Disease

    DEFF Research Database (Denmark)

    Williams, James C; Borofsky, Michael S; Bledsoe, Sharon B

    2018-01-01

    PURPOSE: Mechanisms of early stone retention in the kidney are under studied and poorly understood. To date attachment via Randall's plaque is the only widely accepted theory in this regard, which is best described in idiopathic calcium oxalate stone formers. Brushite stone formers are known...... to have distinct papillary morphology relative to calcium oxalate stone formers. As such we sought to determine whether stone attachment mechanisms in such patients may be similarly unique. MATERIALS AND METHODS: Patients undergoing percutaneous and or ureteroscopic procedures for stone removal consented...... to endoscopic renal papillary examination and individual stone collection. Each removed stone was processed using micro computerized tomography to assess the 3-dimensional microstructure and the minerals contained, and search for common structural features indicative of novel mechanisms of early growth...

  2. Post-transcriptional regulation of macrophage ABCA1, an early response gene to IFN-γ

    International Nuclear Information System (INIS)

    Alfaro Leon, Martha Leticia; Evans, Glenn F.; Farmen, Mark W.; Zuckerman, Steven H.

    2005-01-01

    Interferon-γ (IFN-γ) down-regulates receptors associated with reverse cholesterol transport including ABCA1. In the present study, the kinetics and mechanism of ABCA1 down-regulation were determined in mouse peritoneal macrophages. IFN-γ decreased ABCA1 mRNA 1 h following IFN-γ addition and was maximally reduced by 3 h. Down-regulation was protein synthesis dependent and involved post-transcriptional processes. ABCA1 message had a T 1/2 of 115 min in actinomycin treated cells that was reduced to a T 1/2 of 37 min by IFN-γ. The decrease in message stability was also associated with a rapid loss of ABCA1 protein, significant 3 h following IFN-γ addition. The kinetics of ABCA1 message and protein decrease was consistent with the early IFN-γ-induced changes in Stat1 phosphorylation and nuclear translocation observed in these cells. Therefore, ABCA1 can be considered as an early response gene to macrophage activation by IFN-γ with down-regulation occurring by message destabilization

  3. A hydro-mechanical framework for early warning of rainfall-induced landslides (Invited)

    Science.gov (United States)

    Godt, J.; Lu, N.; Baum, R. L.

    2013-12-01

    Landslide early warning requires an estimate of the location, timing, and magnitude of initial movement, and the change in volume and momentum of material as it travels down a slope or channel. In many locations advance assessment of landslide location, volume, and momentum is possible, but prediction of landslide timing entails understanding the evolution of rainfall and soil-water conditions, and consequent effects on slope stability in real time. Existing schemes for landslide prediction generally rely on empirical relations between landslide occurrence and rainfall amount and duration, however, these relations do not account for temporally variable rainfall nor the variably saturated processes that control the hydro-mechanical response of hillside materials to rainfall. Although limited by the resolution and accuracy of rainfall forecasts and now-casts in complex terrain and by the inherent difficulty in adequately characterizing subsurface materials, physics-based models provide a general means to quantitatively link rainfall and landslide occurrence. To obtain quantitative estimates of landslide potential from physics-based models using observed or forecasted rainfall requires explicit consideration of the changes in effective stress that result from changes in soil moisture and pore-water pressures. The physics that control soil-water conditions are transient, nonlinear, hysteretic, and dependent on material composition and history. In order to examine the physical processes that control infiltration and effective stress in variably saturated materials, we present field and laboratory results describing intrinsic relations among soil water and mechanical properties of hillside materials. At the REV (representative elementary volume) scale, the interaction between pore fluids and solid grains can be effectively described by the relation between soil suction, soil water content, hydraulic conductivity, and suction stress. We show that these relations can be

  4. Studies of Physcomitrella patens reveal that ethylene-mediated submergence responses arose relatively early in land-plant evolution

    KAUST Repository

    Yasumura, Yuki

    2012-10-18

    Colonization of the land by multicellular green plants was a fundamental step in the evolution of life on earth. Land plants evolved from fresh-water aquatic algae, and the transition to a terrestrial environment required the acquisition of developmental plasticity appropriate to the conditions of water availability, ranging from drought to flood. Here we show that extant bryophytes exhibit submergence-induced developmental plasticity, suggesting that submergence responses evolved relatively early in the evolution of land plants. We also show that a major component of the bryophyte submergence response is controlled by the phytohormone ethylene, using a perception mechanism that has subsequently been conserved throughout the evolution of land plants. Thus a plant environmental response mechanism with major ecological and agricultural importance probably had its origins in the very earliest stages of the colonization of the land. © 2012 Blackwell Publishing Ltd.

  5. Proteomic responses reveal the differential effects induced by cadmium in mussels Mytilus galloprovincialis at early life stages.

    Science.gov (United States)

    Xu, Lanlan; Peng, Xiao; Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng

    2016-08-01

    Cadmium (Cd) has become an important metal contaminant and posed severe risk on the organisms in the coastal environments of the Bohai Sea. Marine mussel Mytilus galloprovincialis is widely distributed along the Bohai coast and consumed as seafood by local residents. Evidences indicate that the early stages of marine organisms are more sensitive to metal contaminants. In this study, we applied two-dimensional electrophoresis-based proteomics to characterize the biological effects of Cd (50 μg L(-1)) in the early life stages (D-shape larval and juvenile) of mussels. The different proteomic responses demonstrated the differential responsive mechanisms to Cd exposure in these two early life stages of mussels. In details, results indicated that Cd mainly induced immune and oxidative stresses in both D-shape larval and juvenile mussels via different pathways. In addition, the significant up-regulation of triosephosphate isomerase and metallothionein confirmed the enhanced energy demand and mobilized detoxification mechanism in D-shape larval mussels exposed to Cd. In juvenile mussels, Cd exposure also induced clear apoptosis. Overall, this work suggests that Cd is a potential immune toxicant to mussel M. galloprovincialis at early life stages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Magnetic source localization of early visual mismatch response

    NARCIS (Netherlands)

    Susac, A.; Heslenfeld, D.J.; Huonker, R.; Supek, S.

    2014-01-01

    Previous studies have reported a visual analogue of the auditory mismatch negativity (MMN) response that is based on sensory memory. The neural generators and attention dependence of the visual MMN (vMMN) still remain unclear. We used magnetoencephalography (MEG) and spatio-temporal source

  7. Early transcriptional responses of internalization defective Brucella abortus mutants in professional phagocytes, RAW 264.7.

    Science.gov (United States)

    Cha, Seung Bin; Lee, Won Jung; Shin, Min Kyoung; Jung, Myung Hwan; Shin, Seung Won; Yoo, An Na; Kim, Jong Wan; Yoo, Han Sang

    2013-06-27

    Brucella abortus is an intracellular zoonotic pathogen which causes undulant fever, endocarditis, arthritis and osteomyelitis in human and abortion and infertility in cattle. This bacterium is able to invade and replicate in host macrophage instead of getting removed by this defense mechanism. Therefore, understanding the interaction between virulence of the bacteria and the host cell is important to control brucellosis. Previously, we generated internalization defective mutants and analyzed the envelope proteins. The present study was undertaken to evaluate the changes in early transcriptional responses between wild type and internalization defective mutants infected mouse macrophage, RAW 264.7. Both of the wild type and mutant infected macrophages showed increased expression levels in proinflammatory cytokines, chemokines, apoptosis and G-protein coupled receptors (Gpr84, Gpr109a and Adora2b) while the genes related with small GTPase which mediate intracellular trafficking was decreased. Moreover, cytohesin 1 interacting protein (Cytip) and genes related to ubiquitination (Arrdc3 and Fbxo21) were down-regulated, suggesting the survival strategy of this bacterium. However, we could not detect any significant changes in the mutant infected groups compared to the wild type infected group. In summary, it was very difficult to clarify the alterations in host cellular transcription in response to infection with internalization defective mutants. However, we found several novel gene changes related to the GPCR system, ubiquitin-proteosome system, and growth arrest and DNA damages in response to B. abortus infection. These findings may contribute to a better understanding of the molecular mechanisms underlying host-pathogen interactions and need to be studied further.

  8. Computational modeling predicts the ionic mechanism of late-onset responses in Unipolar Brush Cells

    Directory of Open Access Journals (Sweden)

    Sathyaa eSubramaniyam

    2014-08-01

    Full Text Available Unipolar Brush Cells (UBCs have been suggested to have a strong impact on cerebellar granular layer functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamatergic synaptic responses, a late-onset response (LOR composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013. The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment and axon incorporating biologically realistic representations of ionic currents and a generic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a low-threshold spike sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of delayed bursts, which could take part to the formation of tunable delay-lines in the local microcircuit.

  9. Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells.

    Science.gov (United States)

    Subramaniyam, Sathyaa; Solinas, Sergio; Perin, Paola; Locatelli, Francesca; Masetto, Sergio; D'Angelo, Egidio

    2014-01-01

    Unipolar Brush Cells (UBCs) have been suggested to play a critical role in cerebellar functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamate receptor-dependent synaptic responses, a late-onset response (LOR) composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013). The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment, and axon) incorporating biologically realistic representations of ionic currents and a cytoplasmic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a burst triggered by a low-threshold spike (LTS) sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit.

  10. Features of legal mechanism environmental responsibility of citizens in Ukraine

    Directory of Open Access Journals (Sweden)

    О. О. Шинкарьов

    2015-05-01

    Full Text Available Problem setting. In this article it is examined the main conceptual approaches to understanding the legal arrangement for implementing citizens' environmental obligations. It is noted that despite the diversity of approaches to understanding the arrangement for implementing citizens' environmental responsibilities, most scientists include the concepts of: a a legal implementation arrangement, b the process of practical implementation, c the conditions and factors that influence it.  It is defined that the legal arrangement for implementing environmental obligations is guaranteed by prohibitions and legal regulations. In this case the regulatory legal act has two main functions:    1 prescribes the need to implement the legal obligation, determines it; 2 prescribes a result of the legal obligation implementation. Recent research and publications analysis. Particular attention is paid to the work of scientists in environmental law, including VI Andryeytseva, G. Anisimova, GI Baluk, AP Hetman M. Krasnov, II Karakash, V. Kostytsky, VV Nosik, M. Shulga, S. Shemshuchenko and others. However, most of them concerning coverage of only certain aspects, is a comprehensive analysis of the legal implementation mechanism is still lacking. It's analyzed the characteristics of the legal enforcement for implementing environmental responsibilities by citizens. It is determined that the legal arrangement for the implementation of environmental responsibilities is a part of a general arrangement of the law implementation. Ecological and legal arrangement for the implementation of environmental obligations is defined as a system of legal norms and legal relations by which the State provides the accomplishment of ecological  and legal regulations. Implementation of the constitutional obligations by the citizens is a process that is inherent in environmental responsibilities, in which there are several stages: 1 the ability to execute the obligations which are

  11. Early results of experiments with responsive open learning environments

    OpenAIRE

    Friedrich, M.; Wolpers, M.; Shen, R.; Ullrich, C.; Klamma, R.; Renzel, D.; Richert, A.; Heiden, B. von der

    2011-01-01

    Responsive open learning environments (ROLEs) are the next generation of personal learning environments (PLEs). While PLEs rely on the simple aggregation of existing content and services mainly using Web 2.0 technologies, ROLEs are transforming lifelong learning by introducing a new infrastructure on a global scale while dealing with existing learning management systems, institutions, and technologies. The requirements engineering process in highly populated test-beds is as important as the t...

  12. Early Family Relationships Predict Children’s Emotion Regulation and Defense Mechanisms

    Directory of Open Access Journals (Sweden)

    Jallu Lindblom

    2016-12-01

    Full Text Available Early family relationships have been suggested to influence the development of children’s affect regulation, involving both emotion regulation and defense mechanisms. However, we lack research on the specific family predictors for these two forms of affect regulation, which have been conceptualized to differ in their functions and accessibility to consciousness. Accordingly, we examine how the (a quality and (b timing of family relationships during infancy predict child’s later emotion regulation and defense mechanisms. Parents (N = 703 reported autonomy and intimacy in marital and parenting relationships at the child’s ages of 2 and 12 months, and the child’s use of emotion regulation and immature and neurotic defenses at 7 to 8 years. As hypothesized, the results showed that functional early family relationships predicted children’s efficient emotion regulation, whereas dysfunctional relationships predicted reliance on defense mechanisms in middle childhood. Further, results showed a timing effect for neurotic defenses, partially confirming our hypothesis of early infancy being an especially important period for the development of defense mechanisms. The findings are discussed from the viewpoints of attachment and family dynamics, emotional self-awareness, and sense of security.

  13. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    Science.gov (United States)

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

  14. Collecting response times using Amazon Mechanical Turk and Adobe Flash.

    Science.gov (United States)

    Simcox, Travis; Fiez, Julie A

    2014-03-01

    Crowdsourcing systems like Amazon's Mechanical Turk (AMT) allow data to be collected from a large sample of people in a short amount of time. This use has garnered considerable interest from behavioral scientists. So far, most experiments conducted on AMT have focused on survey-type instruments because of difficulties inherent in running many experimental paradigms over the Internet. This study investigated the viability of presenting stimuli and collecting response times using Adobe Flash to run ActionScript 3 code in conjunction with AMT. First, the timing properties of Adobe Flash were investigated using a phototransistor and two desktop computers running under several conditions mimicking those that may be present in research using AMT. This experiment revealed some strengths and weaknesses of the timing capabilities of this method. Next, a flanker task and a lexical decision task implemented in Adobe Flash were administered to participants recruited with AMT. The expected effects in these tasks were replicated. Power analyses were conducted to describe the number of participants needed to replicate these effects. A questionnaire was used to investigate previously undescribed computer use habits of 100 participants on AMT. We conclude that a Flash program in conjunction with AMT can be successfully used for running many experimental paradigms that rely on response times, although experimenters must understand the limitations of the method.

  15. Pluripotent Stem Cell Studies Elucidate the Underlying Mechanisms of Early Embryonic Development

    Directory of Open Access Journals (Sweden)

    Lingyu Li

    2011-03-01

    Full Text Available Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development.

  16. Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Amaro, Cynthia M; Bello, Jose A; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson

    2018-05-01

    To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. ClinicalTrials.gov: NCT01751724. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia.

    Science.gov (United States)

    Hasan, Shirin; Mosier, Michael J; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

    2017-10-01

    Anemia of critical illness is resistant to exogenous erythropoietin. Packed red blood cells transfusions is the only treatment option, and despite related cost and morbidity, there is a need for alternate strategies. Erythrocyte development can be divided into erythropoietin-dependent and erythropoietin-independent stages. We have shown previously that erythropoietin-dependent development is intact in burn patients and the erythropoietin-independent early commitment stage, which is regulated by β1/β2-adrenergic mechanisms, is compromised. Utilizing the scald burn injury model, we studied erythropoietin-independent late maturation stages and the effect of β1/β2, β-2, or β-3 blockade in burn mediated erythropoietin-resistant anemia. Burn mice were randomized to receive daily injections of propranolol (nonselective β1/β2 antagonist), nadolol (long-acting β1/β2 antagonist), butoxamine (selective β2 antagonist), or SR59230A (selective β3 antagonist) for 6 days after burn. Total bone marrow cells were characterized as nonerythroid cells, early and late erythroblasts, nucleated orthochromatic erythroblasts and enucleated reticulocyte subsets using CD71, Ter119, and Syto-16 by flow cytometry. Multipotential progenitors were probed for MafB expressing cells. Although propranolol improved early and late erythroblasts, only butoxamine and selective β3-antagonist administrations were positively reflected in the peripheral blood hemoglobin and red blood cells count. While burn impeded early commitment and late maturation stages, β1/β2 antagonism increased the early erythroblasts through commitment stages via β2 specific MafB regulation. β3 antagonism was more effective in improving overall red blood cells through late maturation stages. The study unfolds novel β2 and β3 adrenergic mechanisms orchestrating erythropoietin resistant anemia after burn, which impedes both the early commitment stage and the late maturation stages, respectively. Copyright © 2017

  18. Kinetics of the early adaptive response and adaptation threshold dose

    International Nuclear Information System (INIS)

    Mendiola C, M.T.; Morales R, P.

    2003-01-01

    The expression kinetics of the adaptive response (RA) in mouse leukocytes in vivo and the minimum dose of gamma radiation that induces it was determined. The mice were exposed 0.005 or 0.02 Gy of 137 Cs like adaptation and 1h later to the challenge dose (1.0 Gy), another group was only exposed at 1.0 Gy and the damage is evaluated in the DNA with the rehearsal it makes. The treatment with 0. 005 Gy didn't induce RA and 0. 02 Gy causes a similar effect to the one obtained with 0.01 Gy. The RA was show from an interval of 0.5 h being obtained the maximum expression with 5.0 h. The threshold dose to induce the RA is 0.01 Gy and in 5.0 h the biggest quantity in molecules is presented presumably that are related with the protection of the DNA. (Author)

  19. The Role Played by the Family in Shaping Early and Middle Adolescent Civic Responsibility

    Science.gov (United States)

    Lenzi, Michela; Vieno, Alessio; Santinello, Massimo; Nation, Maury; Voight, Adam

    2014-01-01

    Adopting a multi-informant methodology, the current study examines the relative influence of multiple parental characteristics (civic responsibility, encouragement of civic action, parent-youth closeness) on adolescents' civic responsibility (local and global). The participants were 384 early and middle adolescents (47.9% male), randomly selected…

  20. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Peng; Zhang, Huoming; Yu, Boying; Xiong, Liming; Xia, Yiji

    2015-01-01

    in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional

  1. Plasticity of the MAPK signaling network in response to mechanical stress

    NARCIS (Netherlands)

    Pereira, Andrea M; Tudor, Cicerone; Pouille, Philippe-Alexandre; Shekhar, Shashank; Kanger, Johannes S; Subramaniam, Vinod; Martín-Blanco, Enrique

    2014-01-01

    Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK) cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms

  2. Early-Life Nutritional Programming of Cognition-The Fundamental Role of Epigenetic Mechanisms in Mediating the Relation between Early-Life Environment and Learning and Memory Process.

    Science.gov (United States)

    Moody, Laura; Chen, Hong; Pan, Yuan-Xiang

    2017-03-01

    The perinatal period is a window of heightened plasticity that lays the groundwork for future anatomic, physiologic, and behavioral outcomes. During this time, maternal diet plays a pivotal role in the maturation of vital organs and the establishment of neuronal connections. However, when perinatal nutrition is either lacking in specific micro- and macronutrients or overloaded with excess calories, the consequences can be devastating and long lasting. The brain is particularly sensitive to perinatal insults, with several neurologic and psychiatric disorders having been linked to a poor in utero environment. Diseases characterized by learning and memory impairments, such as autism, schizophrenia, and Alzheimer disease, are hypothesized to be attributed in part to environmental factors, and evidence suggests that the etiology of these conditions may date back to very early life. In this review, we discuss the role of the early-life diet in shaping cognitive outcomes in offspring. We explore the endocrine and immune mechanisms responsible for these phenotypes and discuss how these systemic factors converge to change the brain's epigenetic landscape and regulate learning and memory across the lifespan. Through understanding the maternal programming of cognition, critical steps may be taken toward preventing and treating diseases that compromise learning and memory. © 2017 American Society for Nutrition.

  3. Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

    Science.gov (United States)

    Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

    2017-09-01

    Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

  4. Carbonitriding of low alloy steels: Mechanical and metallurgical responses

    Energy Technology Data Exchange (ETDEWEB)

    Dal' Maz Silva, W., E-mail: waltermateriais@me.com [Institut Jean Lamour – UMR CNRS–Université de Lorraine, 7198, Parc de Saurupt, Nancy 54011 (France); Institut de Recherche Technologique M2P, Metz 57070 (France); Dulcy, J., E-mail: jacky.dulcy@univ-lorraine.fr [Institut Jean Lamour – UMR CNRS–Université de Lorraine, 7198, Parc de Saurupt, Nancy 54011 (France); Ghanbaja, J., E-mail: jaafar.ghanbaja@univ-lorraine.fr [Institut Jean Lamour – UMR CNRS–Université de Lorraine, 7198, Parc de Saurupt, Nancy 54011 (France); Redjaïmia, A., E-mail: abdelkrim.redjaimia@univ-lorraine.fr [Institut Jean Lamour – UMR CNRS–Université de Lorraine, 7198, Parc de Saurupt, Nancy 54011 (France); Michel, G., E-mail: gregory.michel@irt-m2p.fr [Institut de Recherche Technologique M2P, Metz 57070 (France); Thibault, S., E-mail: simon.thibault@safran.fr [Safran Tech, Magny les Hameaux (France); Belmonte, T., E-mail: thierry.belmonte@univ-lorraine.fr [Institut Jean Lamour – UMR CNRS–Université de Lorraine, 7198, Parc de Saurupt, Nancy 54011 (France)

    2017-05-02

    Metallurgical and mechanical responses of alloys 16NiCrMo13 and 23MnCrMo5 to the addition of carbon and/or nitrogen were investigated. Diffusion profiles of these interstitial elements were established by atmospheric pressure carburizing, austenitic nitriding, and a sequence of carburizing and nitriding – the carbonitriding. All treatments were performed at 1173 K under CO-H{sub 2} and/or NH{sub 3} based atmospheres. After enrichment, each sample was (i) room-temperature oil-quenched and (ii) immersed in boiling nitrogen prior to (iii) the stress relief treatment. Cross-section hardness profiles were evaluated after each of these steps. Electron probe microanalysis (EPMA) allowed for the determination of both carbon and nitrogen diffusion profiles after quenching. In order to estimate the fraction of nitrides formed during the enrichment of the alloys, these measured profiles were employed in the simulation of local equilibrium at each evaluated position. This allowed for the computation of total solid solution interstitial content, which was expressed in atomic fraction. Plots of as-quenched hardness against the square root of the computed interstitial content, i.e. the sum of solution carbon and the remaining nitrogen, show the complementary character of these elements in determining the mechanical properties of the materials prior to stress relief treatment. Tempering of carbon-nitrogen martensite resulted in hardness drop to a lesser degree than the one measured on carbon martensite with equivalent interstitial content. In order to investigate this behavior, transmission electron microscopy (TEM) analyses were performed. Results showed the precipitation of two morphologies of Fe{sub 16}N{sub 2} in the nitrogen-rich case and image analysis confirmed the simulated fraction of nitrides.

  5. Discrimination of amygdala response predicts future separation anxiety in youth with early deprivation.

    Science.gov (United States)

    Green, Shulamite A; Goff, Bonnie; Gee, Dylan G; Gabard-Durnam, Laurel; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Louie, Jennifer; Tottenham, Nim

    2016-10-01

    mechanism to explain the associations between early caregiving adversity and individual differences in internalizing symptomology during development, thereby contributing to individualized predictions of future clinical outcomes. © 2016 Association for Child and Adolescent Mental Health.

  6. Doppler derived gradient of ST Jude Mechanical Prosthesis, early postoperative assessment

    International Nuclear Information System (INIS)

    Shaikh, A.H.; Hanif, B.; Adil, A.; Hashimi, S.; Qazi, H.A.; Mujtaba, I.

    2010-01-01

    Objective: To determine the doppler derived mean gradients of St Jude mechanical prosthesis in early postoperative period in patients undergoing valve replacement at a tertiary care cardiac centre. Methods: Medical records of 190 consecutive patients who underwent 233 mitral, aortic or dual (mitral and aortic) valve replacement by St Jude bileaflet mechanical prosthesis at Tabba Heart Institute, between March 2006 to December 2008 were reviewed. Doppler derived mean gradients were assessed predischarge and recorded. Results: There were 98 (51.5%) males and 92 (48.5%) females in the study cohort. The mean age was 40 +- 14 years. Of the total, 101 (53%) had mitral, 46 (24.2%) had aortic and 43 (22.6%) patients had dual valve replacement. Doppler derived mean gradient was assessed across 144 mitral and 89 aortic St Jude mechanical prosthesis. Doppler derived mean gradient for St Jude mitral prosthesis was 3.5 mm Hg and for St Jude aortic prosthesis was 10.2 mm Hg. Conclusions: The study determines baseline gradients across mitral and aortic St Jude mechanical prosthesis in our population. These can be used as reference gradients to assess St Jude prosthetic valve function in patients who did not have early postoperative doppler assessment. (author)

  7. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

    Science.gov (United States)

    Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  8. Acid Stress Response Mechanisms of Group B Streptococci

    Directory of Open Access Journals (Sweden)

    Sarah Shabayek

    2017-09-01

    Full Text Available Group B streptococcus (GBS is a leading cause of neonatal mortality and morbidity in the United States and Europe. It is part of the vaginal microbiota in up to 30% of pregnant women and can be passed on to the newborn through perinatal transmission. GBS has the ability to survive in multiple different host niches. The pathophysiology of this bacterium reveals an outstanding ability to withstand varying pH fluctuations of the surrounding environments inside the human host. GBS host pathogen interations include colonization of the acidic vaginal mucosa, invasion of the neutral human blood or amniotic fluid, breaching of the blood brain barrier as well as survival within the acidic phagolysosomal compartment of macrophages. However, investigations on GBS responses to acid stress are limited. Technologies, such as whole genome sequencing, genome-wide transcription and proteome mapping facilitate large scale identification of genes and proteins. Mechanisms enabling GBS to cope with acid stress have mainly been studied through these techniques and are summarized in the current review

  9. Fast-Response electric drives of Mechanical Engineering objects

    Science.gov (United States)

    Doykina, L. A.; Bukhanov, S. S.; Gryzlov, A. A.

    2018-03-01

    The article gives a solution to the problem of increasing the speed in the electrical drives of machine-building enterprises due to the application of a structure with ISC control. In this case, it is possible to get rid of the speed sensors. It is noted that in this case no circulating pulsations are applied to the input of the control system, caused by a non-identical interface between the sensor and the shaft of the operating mechanism. For detailed modeling, a mathematical model of an electric drive with distributed parameters was proposed. The calculation of such system was carried out by the finite element method. Taking into account the distributed characteristic of the system parameters allowed one to take into account the discrete nature of the electric machine’s work. The simulation results showed that the response time in the control circuit is estimated at a time constant of 0.0015, which is about twice as fast as in traditional vector control schemes.

  10. [Nasal CPAP versus mechanical ventilation in 28 to 32-week preterm infants with early surfactant administration].

    Science.gov (United States)

    Pérez, Luis Alfonso; González, Diana Marcela; Álvarez, Karen Margarita de Jesús; Díaz-Martínez, Luis Alfonso

    2014-01-01

    Continuous positive airway pressure (CPAP) is useful in low birth weight infants with respiratory distress, but it is not known if it is a better alternative to mechanical ventilation after early pulmonary surfactant administration. To compare the incidence of adverse events in 28 to 32-week newborns with respiratory distress managed with mechanical ventilation or CPAP after early surfactant administration. In total, 176 newborns were treated with CPAP and 147 with mechanical ventilation, all with Apgar scores >3 at five minutes and without apnea. The incidence of CPAP failure was 6.5% (95% CI: 11.3-22.8%); 29 patients died: 7 with CPAP (4.0%) and 22 with mechanical ventilation (15.0%, pmechanical ventilation was 0.27 (95% CI: 0.12-0.61), but after adjusting for confounding factors, CPAP use did not imply a higher risk of dying (RR=0.60; 95% CI: 0.29-1.24). Mechanical ventilation fatality rate was 5.70 (95% CI: 3.75-8.66) deaths/1,000 days-patient, while with CPAP it was 1.37 (95% CI: 0.65-2.88, pmechanical ventilation (RR=0.71; 95% CI: 0.54-0.96), as were intracranial hemorrhage (RR=0.28, 95% CI: 0.09-0.84) and sepsis (RR=0.67; 95%CI: 0.52-0.86), and it was similar for air leaks (RR=2.51; 95% CI: 0.83-7.61) and necrotizing enterocolitis (RR=1.68, 95% CI: 0.59-4.81). CPAP exposure of premature infants with respiratory distress syndrome is protective against chronic lung disease, intraventricular hemorrhage and sepsis compared to mechanical ventilation. No differences were observed regarding air leak syndrome or death.

  11. Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

    Science.gov (United States)

    Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

    2018-05-01

    The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

  12. SOS response activation and competence development are antagonistic mechanisms in Streptococcus thermophilus.

    Science.gov (United States)

    Boutry, Céline; Delplace, Brigitte; Clippe, André; Fontaine, Laetitia; Hols, Pascal

    2013-02-01

    Streptococcus includes species that either contain or lack the LexA-like repressor (HdiR) of the classical SOS response. In Streptococcus pneumoniae, a species which belongs to the latter group, SOS response inducers (e.g., mitomycin C [Mc] and fluoroquinolones) were shown to induce natural transformation, leading to the hypothesis that DNA damage-induced competence could contribute to genomic plasticity and stress resistance. Using reporter strains and microarray experiments, we investigated the impact of the SOS response inducers mitomycin C and norfloxacin and the role of HdiR on competence development in Streptococcus thermophilus. We show that both the addition of SOS response inducers and HdiR inactivation have a dual effect, i.e., induction of the expression of SOS genes and reduction of transformability. Reduction of transformability results from two different mechanisms, since HdiR inactivation has no major effect on the expression of competence (com) genes, while mitomycin C downregulates the expression of early and late com genes in a dose-dependent manner. The downregulation of com genes by mitomycin C was shown to take place at the level of the activation of the ComRS signaling system by an unknown mechanism. Conversely, we show that a ComX-deficient strain is more resistant to mitomycin C and norfloxacin in a viability plate assay, which indicates that competence development negatively affects the resistance of S. thermophilus to DNA-damaging agents. Altogether, our results strongly suggest that SOS response activation and competence development are antagonistic processes in S. thermophilus.

  13. [Early responses of soil fauna in three typical forests of south subtropical China to simulated N deposition addition].

    Science.gov (United States)

    Xu, Guolian; Mo, Jiangming; Zhou, Guoyi

    2005-07-01

    In this paper, simulated N deposition addition (0, 50, 100 and 150 kg x hm(-2) x yr(-1)) by spreading water or NH4NO3 was conducted to study the early responses of soil fauna in three typical native forests (monsoon evergreen broadleaf forest, pine forest, and broadleaf-pine mixed forest) of subtropical China. The results showed that in monsoon evergreen broadleaf forest, N deposition addition had an obviously negative effect on the three indexes for soil fauna, but in pine forest, the positive effect was significant (P soil fauna community could reach the level in mixed forest, even that in monsoon evergreen broadleaf forest at sometime. The responses in mixed forest were not obvious. In monsoon evergreen broadleaf forest, the negative effects were significant (P soil fauna groups. The results obtained might imply the N saturation-response mechanisms of forest ecosystems in subtropical China, and the conclusions from this study were also consisted with some related researches.

  14. A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides.

    Science.gov (United States)

    Voelz, Kerstin; Gratacap, Remi L; Wheeler, Robert T

    2015-11-01

    Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at increased risk of developing disease. These individuals often present with defects in phagocytic effector cell function. Research using mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory for direct analysis of the interaction between innate immune effector cells and infectious sporangiospores in vivo. Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole-animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swim bladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We showed for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and that spore phagocytosis can be observed in real-time in vivo. While exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by 6 h post-infection in both infection models. After 24 h, induction of a pro-inflammatory response was observed only in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swim bladder during the same time frame. In the future, the zebrafish larva as a live whole

  15. FLT-PET for early response evaluation of colorectal cancer patients with liver metastases

    DEFF Research Database (Denmark)

    Mogensen, Marie Benzon; Loft, Annika; Aznar, Marianne

    2017-01-01

    BACKGROUND: Fluoro-L-thymidine (FLT) is a positron emission tomography/computed tomography (PET/CT) tracer which reflects proliferative activity in a cancer lesion. The main objective of this prospective explorative study was to evaluate whether FLT-PET can be used for the early evaluation...... standardised uptake values (SUVmax, SUVmean) were measured. After three cycles of chemotherapy, treatment response was assessed by CT scan based on RECIST 1.1. RESULTS: Thirty-nine consecutive patients were included of which 27 were evaluable. Dropout was mainly due to disease complications. Nineteen patients...... between the response according to RECIST and the early changes in FLT uptake measured as SUVmax(p = 0.24). CONCLUSIONS: No correlation was found between early changes in FLT uptake after the first cycle of treatment and the response evaluated from subsequent CT scans. It seems unlikely that FLT-PET can...

  16. Exposure to dim light at night during early development increases adult anxiety-like responses.

    Science.gov (United States)

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  17. Conceptual approaches to the formation the mechanism of enterprises social responsibility stimulation

    OpenAIRE

    Ohorodnikova, Natalia

    2014-01-01

    The article defines the economic content of the enterprise social responsibility incentive mechanism, the concept of its perfection. There are formulated the purpose and objectives of the proposed mechanisms, sounded principles of its formation. As tools of the enterprise social responsibility incentive mechanism, it is advised to use: methods of corporate social responsibility stimulating, a model of corporate strategy in the context of implementing the practice of social responsibility in t...

  18. [Inflammasome and its role in immunological and inflammatory response at early stage of burns].

    Science.gov (United States)

    Zhang, Fang; Li, Jiahui; Xia, Zhaofan

    2014-06-01

    Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

  19. Mechanized systems for early stand tending in central and eastern Canada

    Energy Technology Data Exchange (ETDEWEB)

    Ryans, M.; St-Amour, M. [Forest Engineering Research Inst. of Canada, Pointe Claire, PQ (Canada)

    1996-12-31

    Machines are currently being used for early stand tending in central and eastern Canada, but account for only 1 to 2% of the annual total for mechanical treatments (including manual and motor-manual operations). Selective and non-selective systems are used, depending on the application and stand conditions. Plantation cleaning operations and precommercial thinning (spacing) of naturally regenerated and seeded stands have been mechanized. Selective methods, primarily for plantation cleaning, use equipment with specialized prime movers, booms and controls, and cutting heads. This paper describes the Canadian experience to date based on FERIC`s studies of successful and unsuccessful operations, and lists the key features of a machine suitable for use in selective treatments. Strip precommercial thinning is used in denser natural stands, but limited improvements in crop-tree growth occur unless a motor-manual follow-up releases crop trees in the leave strips. Most off-the-shelf brushcutting equipment is not optimal for this application, primarily because it is too wide to meet local spacing prescriptions. Some applications such as the spacing of older natural stands have proven difficult to mechanize. Technical, biological, operational , regulatory, economic and social constraints prevent wider use of mechanized systems. Nonetheless, some machines are in operational use, and mechanized plantation cleaning is tested in some regions as an alternative to herbicides. 11 refs, 2 figs, 1 tab

  20. Thermo-mechanical simulations of early-age concrete cracking with durability predictions

    Science.gov (United States)

    Havlásek, Petr; Šmilauer, Vít; Hájková, Karolina; Baquerizo, Luis

    2017-09-01

    Concrete performance is strongly affected by mix design, thermal boundary conditions, its evolving mechanical properties, and internal/external restraints with consequences to possible cracking with impaired durability. Thermo-mechanical simulations are able to capture those relevant phenomena and boundary conditions for predicting temperature, strains, stresses or cracking in reinforced concrete structures. In this paper, we propose a weakly coupled thermo-mechanical model for early age concrete with an affinity-based hydration model for thermal part, taking into account concrete mix design, cement type and thermal boundary conditions. The mechanical part uses B3/B4 model for concrete creep and shrinkage with isotropic damage model for cracking, able to predict a crack width. All models have been implemented in an open-source OOFEM software package. Validations of thermo-mechanical simulations will be presented on several massive concrete structures, showing excellent temperature predictions. Likewise, strain validation demonstrates good predictions on a restrained reinforced concrete wall and concrete beam. Durability predictions stem from induction time of reinforcement corrosion, caused by carbonation and/or chloride ingress influenced by crack width. Reinforcement corrosion in concrete struts of a bridge will serve for validation.

  1. From Archimedean Hydrostatics to Post-Aristotelian Mechanics: Galileo's Early Manuscripts De motu antiquiora (ca. 1590)

    Science.gov (United States)

    Salvia, Stefano

    2017-06-01

    Galileo's early inquiries on motion and free fall in Pisa (1588-1592) can be regarded as a case study of multiple knowledge transfer at the very basic roots of modern mechanics. The treatise De motu, unpublished until 1890, is an original but unsuccessful attempt to go beyond Aristotelian physics by extending Archimedean hydrostatics to the dynamics of natural motion and reappraising the late-medieval impetus theory to account for violent motion and acceleration. I will discuss in particular why Galileo was forced to abandon his project before moving to Padua and how the manuscripts De motu provided him with a "research agenda" for further theoretical and experimental investigation.

  2. Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

    Science.gov (United States)

    Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

    2017-01-01

    Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

  3. First Steps to School Readiness: South Carolina's Response to At-Risk Early Childhood Population.

    Science.gov (United States)

    Buford, Rhonda; Stegelin, Dolores A.

    2003-01-01

    Describes South Carolina's new state early childhood program, First Steps to School Readiness. Includes a profile of the state's at-risk child population, noting poverty and education risk indicators, and describing key program components. The article discusses program oversight, local program partnerships, program funding mechanisms, and local…

  4. The NRF2-KEAP1 Pathway Is an Early Responsive Gene Network in Arsenic Exposed Lymphoblastoid Cells

    Science.gov (United States)

    Córdova, Emilio J.; Martínez-Hernández, Angélica; Uribe-Figueroa, Laura; Centeno, Federico; Morales-Marín, Mirna; Koneru, Harsha; Coleman, Matthew A.; Orozco, Lorena

    2014-01-01

    Inorganic arsenic (iAs), a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min) and was responsive to low iAs concentrations (0.1 µM), this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs. PMID:24516582

  5. Auditory-neurophysiological responses to speech during early childhood: Effects of background noise.

    Science.gov (United States)

    White-Schwoch, Travis; Davies, Evan C; Thompson, Elaine C; Woodruff Carr, Kali; Nicol, Trent; Bradlow, Ann R; Kraus, Nina

    2015-10-01

    Early childhood is a critical period of auditory learning, during which children are constantly mapping sounds to meaning. But this auditory learning rarely occurs in ideal listening conditions-children are forced to listen against a relentless din. This background noise degrades the neural coding of these critical sounds, in turn interfering with auditory learning. Despite the importance of robust and reliable auditory processing during early childhood, little is known about the neurophysiology underlying speech processing in children so young. To better understand the physiological constraints these adverse listening scenarios impose on speech sound coding during early childhood, auditory-neurophysiological responses were elicited to a consonant-vowel syllable in quiet and background noise in a cohort of typically-developing preschoolers (ages 3-5 yr). Overall, responses were degraded in noise: they were smaller, less stable across trials, slower, and there was poorer coding of spectral content and the temporal envelope. These effects were exacerbated in response to the consonant transition relative to the vowel, suggesting that the neural coding of spectrotemporally-dynamic speech features is more tenuous in noise than the coding of static features-even in children this young. Neural coding of speech temporal fine structure, however, was more resilient to the addition of background noise than coding of temporal envelope information. Taken together, these results demonstrate that noise places a neurophysiological constraint on speech processing during early childhood by causing a breakdown in neural processing of speech acoustics. These results may explain why some listeners have inordinate difficulties understanding speech in noise. Speech-elicited auditory-neurophysiological responses offer objective insight into listening skills during early childhood by reflecting the integrity of neural coding in quiet and noise; this paper documents typical response

  6. Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

    Science.gov (United States)

    This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

  7. A note on the Pazos-Simonsen mechanism and Kaldor's early research on Latin American inflation

    Directory of Open Access Journals (Sweden)

    Leonardo Vera

    2013-06-01

    Full Text Available In contrast with the inflationary finance story, inflation acceleration in Latin America has been explained as the result of the interaction of inflation dynamics and the frequency of wage adjustments. Accordingly, small inflation disturbances are connected with a shift from moderate to high inflation (or beyond to hyperinflation though a mechanism that makes adjustment intervals in wage contracts endogenous. Rudiger Dornbusch (1986 labeled this process the "Pazos-Simonsen mechanism". In this note we summarize the basic contribution of both Felipe Pazos (1978 and Mario Henrique Simonsen (1983 and find crucial differences between their views on wage dynamics, specifically regarding the endogeneity of the time interval between wage readjustments. A remarkable affinity with Pazos's view on wage dynamics and inflation is found in an early and almost unknown essay written by Nicholas Kaldor in 1957 (inspired in his brief experience in Latin America.

  8. Temperature extremes in Europe: mechanisms and responses to climatic change

    International Nuclear Information System (INIS)

    Cattiaux, Julien

    2010-01-01

    Europe witnessed a spate of record-breaking warm seasons during the 2000's. As illustrated by the devastating heat-wave of the summer 2003, these episodes induced strong societal and environmental impacts. Such occurrence of exceptional events over a relatively short time period raised up many questionings in the present context of climate change. In particular, can recent temperature extremes be considered as 'previews' of future climate conditions? Do they result from an increasing temperature variability? These questions constitute the main motivations of this thesis. Thus, our work aims to contribute to the understanding of physical mechanisms responsible for seasonal temperature extremes in Europe, in order to anticipate their future statistical characteristics. Involved processes are assessed by both statistical data-analysis of observations and climate projections and regional modeling experiments. First we show that while the inter-annual European temperature variability appears driven by disturbances in the North-Atlantic dynamics, the recent warming is likely to be dissociated with potential circulation changes. This inconsistency climaxes during the exceptionally mild autumn of 2006, whose temperature anomaly is only half explained by the atmospheric flow. Recent warm surface conditions in the North-Atlantic ocean seem to substantially contribute to the European warming in autumn-winter, through the establishment of advective and radiative processes. In spring-summer, since both advection by the westerlies and Atlantic warming are reduced, more local processes appear predominant (e.g. soil moisture, clouds, aerosols). Then the issue of future evolution of the relationship between North-Atlantic dynamics and European temperatures is addressed, based on climate projections of the International Panel on Climate Change. Multi-model analysis, using both flow-analogues and weather regimes methods, show that the inconsistency noticed over recent decades is

  9. Dynamic compressive mechanical response of a soft polymer material

    NARCIS (Netherlands)

    Fan, J.T.; Weerheijm, J.; Sluys, L.J.

    2015-01-01

    The dynamic mechanical behaviour of a soft polymer material (Clear Flex 75) was studied using a split Hopkinson pressure bar (SHPB) apparatus. Mechanical properties have been determined at moderate to high strain rates. Real time deformation and fracture were recorded using a high-speed camera.

  10. Research on working property and early age mechanical property of self-compacting concrete used in steel-concrete structure

    International Nuclear Information System (INIS)

    Zhao Yongguang

    2013-01-01

    Background: Self-compacting concrete that has good working property is the prerequisite of steel-concrete structure. The early age mechanical property of self-compacting concrete is the important parameter when design steel-concrete structure. Purpose: This paper attempts to research the working property and early age mechanical property of self-compacting concrete. Methods: Test is used to research the working property and early age mechanical property of self-compacting concrete. Results: Self-compacting concrete that could meet the requirement of steel-concrete structure has been mixed and parameters of early age mechanical property of self-compacting concrete which is necessary for design of steel-concrete structure have been presented. Conclusions: Base on the results, this paper can guide the construction of self-compacting concrete in steel-concrete structure and the design and construction of steel-concrete structure. (author)

  11. Endocrine and metabolic mechanisms linking postpartum glucose with early embryonic and foetal development in dairy cows.

    Science.gov (United States)

    Lucy, M C; Butler, S T; Garverick, H A

    2014-05-01

    Milk and milk solids production per cow is increasing annually in dairy systems. Peak milk production is in early lactation when the uterus and ovary are recovering from the previous pregnancy. The competing processes of milk production and restoration of reproductive function can be at odds, particularly if unique homeorhetic mechanisms that typify early lactation become imbalanced and cows experience metabolic disease. Homeorhesis leads to an increase in the synthesis of glucose that is irreversibly lost to milk lactose. Irreversible loss of glucose during lactation can invoke an endocrine and metabolic state that impinges upon postpartum uterine health, oestrous cyclicity and subsequent establishment of pregnancy. The first 30 days postpartum may be most critical in terms of the impact that metabolites and metabolic hormones have on reproduction. Depressed immune function caused in part by the postpartum metabolic profile leads to a failure in uterine involution and uterine disease. Oestrous cyclicity (interval to first ovulation and subsequent periodicity) is affected by the same hormones and metabolites that control postpartum immune function. Slower growth of the embryo or foetus perhaps explained by the unique metabolic profile during lactation may predispose cows to pregnancy loss. Understanding homeorhetic mechanisms that involve glucose and collectively affect postpartum uterine health, oestrous cyclicity and the establishment of pregnancy should lead to methods to improve postpartum fertility in dairy cows.

  12. Study on the mechanism of retinal ganglion cell apoptosis in early stage of diabetic rats

    Directory of Open Access Journals (Sweden)

    Rui-Dong Gu

    2014-03-01

    Full Text Available AIM: To investigate the mechanism of retinal ganglion cell apoptosis in early stage of streptozotocin(STZ-induced diabetic rats. METHODS: Sixty SD rats were randomly divided into two groups: control group(CONand diabetes mellitus group(DM. Diabetic rat model was produced by intraperitoneal injection of 1% STZ in 30 adult male SD rats. At 4, 8, 12wk,the rats were killed and eyeballs were enucleated for the HE staining, TUNEL staining, transmission electron microscopy detection respectively, and laser confocal microscope detection was used to detect the calcium ion concentration.RESULTS:At 8wk RGCs decreased gradually and appeared disordered arrangement and got worse at 12wk in DM group. In DM group, mitochondrial swelling was detected at 4wk., and became more obvious, more in number at 8wk with reduction in some cells' volume and the number of organelles decreased. In DM group, few TUNEL positive RGCs were seen at 4wk, and became more and more at 8 and 12wk. The apoptosis index was significantly higher in DM group compared with CON group in different time points(PPPCONCLUSION: The study suggested that RGCs apoptosis occurs in early stage of diabetes, the mechanism might be associated with increased intracellular calcium ion concentration.

  13. Early positron emission tomography response-adapted treatment in stage I and II hodgkin lymphoma

    DEFF Research Database (Denmark)

    André, Marc P.E.; Girinsky, Théodore; Federico, Massimo

    2017-01-01

    Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed...

  14. Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense.

    NARCIS (Netherlands)

    Vos, J.B.; Sterkenburg, M.A. van; Rabe, K.F.; Schalkwijk, J.; Hiemstra, P.S.; Datson, N.A.

    2005-01-01

    The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or

  15. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...

  16. Early pathogenesis and inflammatory response in experimental bovine mastitis due to Streptococcus uberis

    DEFF Research Database (Denmark)

    Pedersen, L.H.; Aalbæk, B.; Røntved, C.M.

    2003-01-01

    A generally similar clinical response was observed in six lactating Holstein-Friesian cows after intramammary inoculation with approximately 107 colony-forming units of Streptococcus uberis. Increased concentrations of serum amyloid A (SAA) were measured in both milk and serum taken 6 and 11 h af...... proteins as potential diagnostic markers for the early detection of S. uberis-associated mastitis....

  17. Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

    Science.gov (United States)

    Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

    2015-01-01

    Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

  18. Conventional estimating method of earthquake response of mechanical appendage system

    International Nuclear Information System (INIS)

    Aoki, Shigeru; Suzuki, Kohei

    1981-01-01

    Generally, for the estimation of the earthquake response of appendage structure system installed in main structure system, the method of floor response analysis using the response spectra at the point of installing the appendage system has been used. On the other hand, the research on the estimation of the earthquake response of appendage system by the statistical procedure based on probability process theory has been reported. The development of a practical method for simply estimating the response is an important subject in aseismatic engineering. In this study, the method of estimating the earthquake response of appendage system in the general case that the natural frequencies of both structure systems were different was investigated. First, it was shown that floor response amplification factor was able to be estimated simply by giving the ratio of the natural frequencies of both structure systems, and its statistical property was clarified. Next, it was elucidated that the procedure of expressing acceleration, velocity and displacement responses with tri-axial response spectra simultaneously was able to be applied to the expression of FRAF. The applicability of this procedure to nonlinear system was examined. (Kako, I.)

  19. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    Science.gov (United States)

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

  20. Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI

    Directory of Open Access Journals (Sweden)

    Alina Tudorica

    2016-02-01

    Full Text Available The purpose is to compare quantitative dynamic contrast-enhanced (DCE magnetic resonance imaging (MRI metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT and evaluation of residual cancer burden (RCB. Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors guidelines. Pharmacokinetic analyses of DCE-MRI data were performed with the standard Tofts and Shutter-Speed models (TM and SSM. After one NACT cycle the percent changes of DCE-MRI parameters Ktrans (contrast agent plasma/interstitium transfer rate constant, ve (extravascular and extracellular volume fraction, kep (intravasation rate constant, and SSM-unique τi (mean intracellular water lifetime are good to excellent early predictors of pathologic complete response (pCR vs. non-pCR, with univariate logistic regression C statistics value in the range of 0.804 to 0.967. ve values after one cycle and at NACT midpoint are also good predictors of response, with C ranging 0.845 to 0.897. However, RECIST LD changes are poor predictors with C = 0.609 and 0.673, respectively. Post-NACT Ktrans, τi, and RECIST LD show statistically significant (P < .05 correlations with RCB. The performances of TM and SSM analyses for early prediction of response and RCB evaluation are comparable. In conclusion, quantitative DCE-MRI parameters are superior to imaging tumor size for early prediction of therapy response. Both TM and SSM analyses are effective for therapy response evaluation. However, the τi parameter derived only with SSM analysis allows the unique opportunity to potentially quantify therapy-induced changes in tumor energetic metabolism.

  1. [Health threats and health system crises. An approach to early warning and response. 2008 SESPAS Report].

    Science.gov (United States)

    Simón Soria, Fernando; Guillén Enríquez, Francisco Javier

    2008-04-01

    The world is changing more and faster than ever before. New diseases are coming to light each year, controlled diseases are reemerging as potential threats, and natural or man-made disasters are increasingly affecting human health. The "International Health Regulations (2005)" reflect the changes in the response of public health to this new situation. Surveillance of specific diseases and predefined control measures have been replaced by surveillance of public health events of international concern and control measures adapted to each situation. The public health events of international interest are characterized by their seriousness, predictability, the risk of international spread and potential for travel or trade restrictions. The development of the European Early Warning and Response System in 1998 and the creation of the European Center for Disease Prevention and Control in 2005 demonstrate political commitment in Europe, with early detection of and response to public health threats. However, timely risk evaluation and response at a national level requires improved data digitalization and accessibility, automatic notification processes, data analysis and dissemination of information, the combination of information from multiple sources and adaptation of public health services. The autonomous regions in Spain are initiating this adaptation process, but interoperability between systems and the development of guidelines for a coordinated response should be steered by the National Interregional Health Council and coordinated by the Ministry of Health. Efficient early warning systems of health threats that allow for a timely response and reduce uncertainty about information would help to minimize the risk of public health crises. The profile of public health threats is nonspecific. Early detection of threats requires access to information from multiple sources and efficient risk assessment. Key factors for improving the response to public health threats are the

  2. The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

    Directory of Open Access Journals (Sweden)

    Michael Nevels

    2009-11-01

    Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

  3. Mechanical response of collagen molecule under hydrostatic compression

    International Nuclear Information System (INIS)

    Saini, Karanvir; Kumar, Navin

    2015-01-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.

  4. Mechanical response of collagen molecule under hydrostatic compression.

    Science.gov (United States)

    Saini, Karanvir; Kumar, Navin

    2015-04-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials. Copyright © 2015 Elsevier B.V. All rights

  5. Mechanical response of collagen molecule under hydrostatic compression

    Energy Technology Data Exchange (ETDEWEB)

    Saini, Karanvir, E-mail: karans@iitrpr.ac.in; Kumar, Navin

    2015-04-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.

  6. Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

    Science.gov (United States)

    Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

    2015-10-01

    Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

  7. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    Science.gov (United States)

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

  8. Involvement of two microRNAs in the early immune response to DNA vaccination against a fish rhabdovirus

    DEFF Research Database (Denmark)

    Bela-ong, Dennis Berbulla; Schyth, Brian Dall; Zou, Jun

    2015-01-01

    Mechanisms that account for the high protective efficacy in teleost fish of a DNA vaccine expressing the glycoprotein (G) of Viral hemorrhagic septicemia virus (VHSV) are thought to involve early innate immune responses mediated by interferons (IFNs). Microribonucleic acids (miRNAs) are a diverse...... class of small (18–22 nucleotides) endogenous RNAs that potently mediate post-transcriptional silencing of a wide range of genes and are emerging as critical regulators of cellular processes, including immune responses. We have recently reported that miR-462 and miR-731 were strongly induced in rainbow......RNAs using anti-miRNA oligonucleotides was conducted in poly I:C-treated rainbow trout fingerlings. Following VHSV challenge, anti-miRNA-injected fish had faster development of disease and higher mortalities than control fish, indicating that miR-462/731 may be involved in IFN-mediated protection conferred...

  9. Uncovering the exposure mechanisms of sunken heavy oil that makes it chronically toxic to early life stages of fish

    International Nuclear Information System (INIS)

    Martin, J.; Young, G.; Lemire, B.; Hodson, P.

    2010-01-01

    A train derailment in 2005 caused the release of 150,000 litres of No. 6 heavy fuel oil into a lake in Alberta. The oil is a residue of the crude oil refinement process and contains 3-4 ringed alkylated forms of polycyclic aromatic hydrocarbons (PAH) that are known to cause sub-lethal toxic responses during the early life stages of rainbow trout. Because the oil does not disperse well, oil patches still persist in near-shore sediments of the lake where fish spawn. This study assessed how the behaviour of heavy oil in water interacts with exposure and toxicity to the early life stages of fish. Daily renewal tests with heavy fuel oil coated on glass plate demonstrated higher levels of toxicity to trout embryos than oil that was mechanically or chemically dispersed. A flow-through oil gravel column was used to assess whether the toxic constituents of the heavy oil are transferred quickly enough to cause toxicity. The aim of the study was to develop exposure and toxicity test methods that accurately reflect the behaviour of heavy oil after a spill.

  10. Mechanical and rheological response of polypropylene/boehmite nanocomposites

    CSIR Research Space (South Africa)

    Pedrazzoli, D

    2014-01-01

    Full Text Available In this work the influence of synthetic boehmite alumina (BA) nanoparticles with various surface treatments on the morphology, crystallization behavior and mechanical properties of polypropylene copolymer (PP) nanocomposites was studied...

  11. Molecular mechanisms of plant competition: neighbour detection and response strategies

    NARCIS (Netherlands)

    Pierik, R.; Mommer, L.; Voesenek, L.A.C.J.

    2013-01-01

    Plant competition determines the diversity and species abundance of natural communities as well as potential yields in agricultural systems. Understanding the mechanisms of plant competition is instrumental to understanding plant performance in true vegetations. In this review, we will address

  12. The effect of ghrelin upon the early immune response in lean and obese mice during sepsis.

    Directory of Open Access Journals (Sweden)

    Daniel Siegl

    Full Text Available It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis.In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis.In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-α concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement.In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice.

  13. The Role of Instabilities on the Mechanical Response of Cellular Solids and Structures

    National Research Council Canada - National Science Library

    Kyriakides, S

    1997-01-01

    .... The relatively regular and periodic microstructure of these two-dimensional materials makes them excellent models for studying the mechanisms that govern the compressive response of cellular materials...

  14. Early lactation feed intake and milk yield responses of dairy cows offered grass silages harvested at early maturity stages

    DEFF Research Database (Denmark)

    Randby, A T; Weisbjerg, M R; Nørgaard, P

    2012-01-01

    was available in automatic feed stations. Intake of grass silage when fed as the sole feed was 16.9 kg of DM on average for lactation wk 1 to 16. When H1 was supplemented with 4 or 8 kg of concentrates, silage DM intake did not change, but total DM intake increased to 20.6 and 23.7 kg/d, respectively. Energy......The main objective was to evaluate the potential of grass silages of very high quality to support a high milk yield with a low or moderate, or even without concentrate supplementation. Production responses to increased levels of concentrate supplementation with 3 primary growth grass silages...... differing in digestibility were studied using 66 Norwegian Red dairy cows. Roundbale silage was produced from a timothy-dominated sward at very early (H1), early (H2), and normal (H3) stages of crop maturity. Crops were rapidly wilted (h) and a formic acid-based additive was applied. All silages were...

  15. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    Science.gov (United States)

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  16. Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.

    Science.gov (United States)

    Kim, Jinho; Jeong, Yong

    2013-01-01

    Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic AβPP(SWE)/PS1ΔE9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.

  17. Hybrid Polymer-Network Hydrogels with Tunable Mechanical Response

    Directory of Open Access Journals (Sweden)

    Sebastian Czarnecki

    2016-03-01

    Full Text Available Hybrid polymer-network gels built by both physical and covalent polymer crosslinking combine the advantages of both these crosslinking types: they exhibit high mechanical strength along with excellent fracture toughness and extensibility. If these materials are extensively deformed, their physical crosslinks can break such that strain energy is dissipated and irreversible fracturing is restricted to high strain only. This mechanism of energy dissipation is determined by the kinetics and thermodynamics of the physical crosslinking contribution. In this paper, we present a poly(ethylene glycol (PEG based material toolkit to control these contributions in a rational and custom fashion. We form well-defined covalent polymer-network gels with regularly distributed additional supramolecular mechanical fuse links, whose strength of connectivity can be tuned without affecting the primary polymer-network composition. This is possible because the supramolecular fuse links are based on terpyridine–metal complexation, such that the mere choice of the fuse-linking metal ion adjusts their kinetics and thermodynamics of complexation–decomplexation, which directly affects the mechanical properties of the hybrid gels. We use oscillatory shear rheology to demonstrate this rational control and enhancement of the mechanical properties of the hybrid gels. In addition, static light scattering reveals their highly regular and well-defined polymer-network structures. As a result of both, the present approach provides an easy and reliable concept for preparing hybrid polymer-network gels with rationally designed properties.

  18. Early and late rate of force development: differential adaptive responses to resistance training?

    DEFF Research Database (Denmark)

    Andersen, L L; Andersen, Jesper Løvind; Zebis, M K

    2010-01-01

    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young......-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force....... males participated in a 14-week resistance training intervention for the lower body and 10 matched subjects participated as controls. Maximal muscle strength (MVC) and RFD were measured during maximal voluntary isometric contraction of the quadriceps femoris muscle. Muscle biopsies were obtained from...

  19. Features of structural response of mechanically loaded crystallites to irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Korchuganov, Aleksandr V., E-mail: avkor@ispms.ru [Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation); National Research Tomsk State University, Tomsk, 634050 (Russian Federation)

    2015-10-27

    A molecular dynamics method is employed to investigate the origin and evolution of plastic deformation in elastically deformed iron and vanadium crystallites due to atomic displacement cascades. Elastic stress states of crystallites result from different degrees of specimen deformation. Crystallites are deformed under constant-volume conditions. Atomic displacement cascades with the primary knock-on atom energy up to 50 keV are generated in loaded specimens. It is shown that irradiation may cause not only the Frenkel pair formation but also large-scale structural rearrangements outside the irradiated area, which prove to be similar to rearrangements proceeding by the twinning mechanism in mechanically loaded specimens.

  20. The Early Development of Human Mirror Mechanisms: Evidence from Electromyographic Recordings at 3 and 6 Months

    Science.gov (United States)

    Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

    2013-01-01

    In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…

  1. Girls’ challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms

    Directory of Open Access Journals (Sweden)

    Melynda D. Casement

    2014-04-01

    Full Text Available Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC, striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence.

  2. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    Science.gov (United States)

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  3. The dynamic and quasi-static mechanical response of three aluminum armor alloys: 5059, 5083 and 7039

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Bergquist, Sara J., E-mail: sara.perezbergquist@gmail.com [Materials Science and Technology Division, Los Alamos National Laboratory, NM 87545 (United States); Gray, G.T.; Cerreta, Ellen K.; Trujillo, Carl P.; Perez-Bergquist, Alex [Materials Science and Technology Division, Los Alamos National Laboratory, NM 87545 (United States)

    2011-11-15

    Highlights: {yields} Aluminum alloys for use in armor applications. {yields} Mechanical response in dynamic and quasi-static regimes with temperature dependence. {yields} Shear localization with evidence of early stages of dynamic recrystallization. - Abstract: The mechanical response and microstructural evolution of aluminum alloys 5083, 5059 and 7039 was examined in compression and shear in both the quasi-static (0.001 s{sup -1}) and dynamic ({approx}2000 s{sup -1}) strain rate regimes. Electron Back Scattered Diffraction was utilized for detailed post-mortem analysis of the specimens following loading. The mechanical responses in shear were found to be strain-rate sensitive. At the slowest strain rates, all of the alloys had relatively large volumes of highly deformed material with 5083 and 5059 having the largest shear affected volumes. The dynamic strain rate test samples all formed highly compact shear localized volumes across the sheared zone with 7039 consistently displaying the narrowest shear regions. The morphology of these shear bands, along with the limited hardening during deformation, indicate a mechanism change at the higher strain rates. Higher resolution orientation image mapping has shown that between the three alloys there are varying degrees of crystallographic order within the shear bands. Transmission electron microscopy revealed various stages of dynamic recrystallization were present suggesting that while low strain rate deformation is controlled by dislocation multiplication and glide, high strain and strain-rate deformation is influenced in part due to mechanical recrystallization.

  4. 3D computational mechanics elucidate the evolutionary implications of orbit position and size diversity of early amphibians.

    Directory of Open Access Journals (Sweden)

    Jordi Marcé-Nogué

    Full Text Available For the first time in vertebrate palaeontology, the potential of joining Finite Element Analysis (FEA and Parametrical Analysis (PA is used to shed new light on two different cranial parameters from the orbits to evaluate their biomechanical role and evolutionary patterns. The early tetrapod group of Stereospondyls, one of the largest groups of Temnospondyls is used as a case study because its orbits position and size vary hugely within the members of this group. An adult skull of Edingerella madagascariensis was analysed using two different cases of boundary and loading conditions in order to quantify stress and deformation response under a bilateral bite and during skull raising. Firstly, the variation of the original geometry of its orbits was introduced in the models producing new FEA results, allowing the exploration of the ecomorphology, feeding strategy and evolutionary patterns of these top predators. Secondly, the quantitative results were analysed in order to check if the orbit size and position were correlated with different stress patterns. These results revealed that in most of the cases the stress distribution is not affected by changes in the size and position of the orbit. This finding supports the high mechanical plasticity of this group during the Triassic period. The absence of mechanical constraints regarding the orbit probably promoted the ecomorphological diversity acknowledged for this group, as well as its ecological niche differentiation in the terrestrial Triassic ecosystems in clades as lydekkerinids, trematosaurs, capitosaurs or metoposaurs.

  5. 3D Computational Mechanics Elucidate the Evolutionary Implications of Orbit Position and Size Diversity of Early Amphibians

    Science.gov (United States)

    Marcé-Nogué, Jordi; Fortuny, Josep; De Esteban-Trivigno, Soledad; Sánchez, Montserrat; Gil, Lluís; Galobart, Àngel

    2015-01-01

    For the first time in vertebrate palaeontology, the potential of joining Finite Element Analysis (FEA) and Parametrical Analysis (PA) is used to shed new light on two different cranial parameters from the orbits to evaluate their biomechanical role and evolutionary patterns. The early tetrapod group of Stereospondyls, one of the largest groups of Temnospondyls is used as a case study because its orbits position and size vary hugely within the members of this group. An adult skull of Edingerella madagascariensis was analysed using two different cases of boundary and loading conditions in order to quantify stress and deformation response under a bilateral bite and during skull raising. Firstly, the variation of the original geometry of its orbits was introduced in the models producing new FEA results, allowing the exploration of the ecomorphology, feeding strategy and evolutionary patterns of these top predators. Secondly, the quantitative results were analysed in order to check if the orbit size and position were correlated with different stress patterns. These results revealed that in most of the cases the stress distribution is not affected by changes in the size and position of the orbit. This finding supports the high mechanical plasticity of this group during the Triassic period. The absence of mechanical constraints regarding the orbit probably promoted the ecomorphological diversity acknowledged for this group, as well as its ecological niche differentiation in the terrestrial Triassic ecosystems in clades as lydekkerinids, trematosaurs, capitosaurs or metoposaurs. PMID:26107295

  6. The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

    Science.gov (United States)

    Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

    2018-03-13

    This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

  7. The crucial effect of early-stage gelation on the mechanical properties of cement hydrates

    Science.gov (United States)

    Ioannidou, Katerina; Kanduč, Matej; Li, Lunna; Frenkel, Daan; Dobnikar, Jure; Del Gado, Emanuela

    2016-07-01

    Gelation and densification of calcium-silicate-hydrate take place during cement hydration. Both processes are crucial for the development of cement strength, and for the long-term evolution of concrete structures. However, the physicochemical environment evolves during cement formation, making it difficult to disentangle what factors are crucial for the mechanical properties. Here we use Monte Carlo and Molecular Dynamics simulations to study a coarse-grained model of cement formation, and investigate the equilibrium and arrested states. We can correlate the various structures with the time evolution of the interactions between the nano-hydrates during the preparation of cement. The novel emerging picture is that the changes of the physicochemical environment, which dictate the evolution of the effective interactions, specifically favour the early gel formation and its continuous densification. Our observations help us understand how cement attains its unique strength and may help in the rational design of the properties of cement and related materials.

  8. Hydrologic response of mechanical mastication in juniper woodland in Utah

    Science.gov (United States)

    Various vegetation control methods have been used to reduce juniper (Juniperus ssp.) woodland encroachment. Mechanical mastication (reducing trees to a mulch residue) has recently been used in some western states. We investigated the hydrologic impacts of rubber tire tracks from the masticating vehi...

  9. Prediction of Early Response to Chemotherapy in Lung Cancer by Using Diffusion-Weighted MR Imaging

    Directory of Open Access Journals (Sweden)

    Jing Yu

    2014-01-01

    Full Text Available Purpose. To determine whether change of apparent diffusion coefficient (ADC value could predict early response to chemotherapy in lung cancer. Materials and Methods. Twenty-five patients with advanced non-small cell lung cancer underwent chest MR imaging including DWI before and at the end of the first cycle of chemotherapy. The tumor’s mean ADC value and diameters on MR images were calculated and compared. The grouping reference was based on serial CT scans according to Response Evaluation Criteria in Solid Tumors. Logistic regression was applied to assess treatment response prediction ability of ADC value and diameters. Results. The change of ADC value in partial response group was higher than that in stable disease group (P=0.004. ROC curve showed that ADC value could predict treatment response with 100% sensitivity, 64.71% specificity, 57.14% positive predictive value, 100% negative predictive value, and 82.7% accuracy. The area under the curve for combination of ADC value and longest diameter change was higher than any parameter alone (P≤0.01. Conclusions. The change of ADC value may be a sensitive indicator to predict early response to chemotherapy in lung cancer. Prediction ability could be improved by combining the change of ADC value and longest diameter.

  10. Molecular Mechanism of the Early Stage of Amyloidogenic Hexapeptides (NFGAIL) Aggregation

    International Nuclear Information System (INIS)

    Shi Bi-Yun; Zhou Bo; Cai Zhuo-Wei; Yang Zai-Xing; Xiu Peng

    2013-01-01

    Peptides/proteins aggregation can give rise to pathological conditions of many human diseases. Small partially ordered oligomers formed in the early stage of aggregation, rather than mature fibrils, are thought to be the main toxicity agent for the living cell. Thus, understanding the pathway and the underlying physical mechanism in the early stage of aggregation is very important for prevention and treatment of these protein functional diseases. Herein we use all-atom molecular dynamics simulations to study the aggregation of four NFGAIL hexapeptides (NFGAIL peptide is a core segment of human islet amyloid polypeptide and exhibits similar aggregation kinetics as the full-length polypeptide). We observe that the peptide monomers in water mainly adopt non-structural coil configurations; the four peptides which are randomly placed in water aggregate spontaneously to partially ordered oligomer (β-sheets) through dimerization or trimerization, with the dimerization predominated. Both parallel and anti-parallel β-sheets are observed. The hydrophobic interactions drive the initial peptides associations, and the subsequent conformational fluctuations promote the formation of more hydrogen bonds between the dangling hydrogen sites in the main chains of peptides. (interdisciplinary physics and related areas of science and technology)

  11. Thermo-Mechanical Methodology for Stabilizing Shape Memory Alloy Response

    Science.gov (United States)

    Padula, Santo

    2013-01-01

    This innovation is capable of significantly reducing the amount of time required to stabilize the strain-temperature response of a shape memory alloy (SMA). Unlike traditional stabilization processes that take days to weeks to achieve stabilized response, this innovation accomplishes stabilization in a matter of minutes, thus making it highly useful for the successful and practical implementation of SMA-based technologies in real-world applications. The innovation can also be applied to complex geometry components, not just simple geometries like wires or rods.

  12. Early Transcriptomic Response to LDL and oxLDL in Human Vascular Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Salvador Damián-Zamacona

    Full Text Available Although nowadays it is well known that the human transcriptome can importantly vary according to external or environmental condition, the reflection of this concept when studying oxidative stress and its direct relationship with gene expression profiling during the process of atherogenesis has not been thoroughly achieved.The ability to analyze genome-wide gene expression through transcriptomics has shown that the genome responds dynamically to diverse stimuli. Here, we describe the transcriptome of human vascular smooth muscle cells (hVSMC stimulated by native and oxidized low-density lipoprotein (nLDL and oxLDL respectively, with the aim of assessing the early molecular changes that induce a response in this cell type resulting in a transcriptomic transformation. This expression has been demonstrated in atherosclerotic plaques in vivo and in vitro, particularly in the light of the oxidative modification hypothesis of atherosclerosis.Total RNA was isolated with TRIzol reagent (Life Technologies and quality estimated using an Agilent 2100 bioanalyzer. The transcriptome of hVSMC under different experimental conditions (1,5 and 24 hours for nLDL and oxLDL was obtained using the GeneChip Human Gene 1.0 ST (Affymetrix designed to measure gene expression of 28,869 well-annotated genes. A fixed fold-change cut-off corresponding to ± 2 was used to identify genes exhibiting the most significant variation and statistical significance (P< 0.05, and 8 genes validated by qPCR using Taqman probes.10 molecular processes were significantly affected in hVSMC: Apoptosis and cell cycle, extracellular matrix remodeling, DNA repair, cholesterol efflux, cGMP biosynthesis, endocytic mechanisms, calcium homeostasis, redox balance, membrane trafficking and finally, the immune response to inflammation. The evidence we present supporting the hypothesis for the involvement of oxidative modification of several processes and metabolic pathways in atherosclerosis is

  13. Analysis of Factors Responsible for Low Utilization of Mechanical ...

    African Journals Online (AJOL)

    The study is concerned with identifying the problems of low utilization of plant and equipment by the indigenous building construction firms in Nigeria. The methodology involved the use of a well structured questionnaire complemented with an oral interview. The results revealed that (15) factors were responsible for low ...

  14. Mechanisms of the training response in patients with peripheral ...

    African Journals Online (AJOL)

    by Gardner et al.18 of 21 studies on exercise training in patients with PAD, PFWD increased 179% and the .... causes an inequality in the supply of and demand for oxygen. Aerobic generation of ATP becomes .... Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of endothelium in the vasodilator response to increased flow ...

  15. Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

    Directory of Open Access Journals (Sweden)

    Reinhard Meier

    Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

  16. Conceptual developments of non-equilibrium statistical mechanics in the early days of Japan

    Science.gov (United States)

    Ichiyanagi, Masakazu

    1995-11-01

    This paper reviews the research in nonequilibrium statistical mechanics made in Japan in the period between 1930 and 1960. Nearly thirty years have passed since the discovery of the exact formula for the electrical conductivity. With the rise of the linear response theory, the methods and results of which are quickly grasped by anyone, its rationale was pushed aside and even at the stage where the formulation was still incomplete some authors hurried to make physical applications. Such an attitude robbed it of most of its interest for the average physicist, who would approach an understanding of some basic concept, not through abstract and logical analysis but by simply increasing his technical experiences with the concept. The purpose of this review is to rescue the linear response theory from being labeled a mathematical tool and to show that it has considerable physical content. Many key papers, originally written in Japanese, are reproduced.

  17. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Zivkovic AR

    2016-11-01

    Full Text Available Aleksandar R Zivkovic, Jochen Bender, Thorsten Brenner, Stefan Hofer,* Karsten Schmidt* Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Purpose: Early diagnosis of systemic inflammatory response syndrome is fundamentally important for an effective and a goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase [BChE] is the major Ach hydrolyzing enzyme in blood. The role of this enzyme during inflammation has not yet been fully understood. This study tests whether a reduction in the BChE activity could indicate the onset of the systemic inflammatory response upon traumatic injury. Patients and methods: This observational study measured BChE activity in patients with traumatic injury admitted to the emergency room by using point-of-care-test system (POCT. In addition, the levels of routine inflammation biomarkers during the initial treatment period were measured. Injury Severity Score was used to assess the trauma severity. Results: Altered BChE activity was correlated with trauma severity, resulting in systemic inflammation. Reduction in the BChE activity was detected significantly earlier compared to those of routinely measured inflammatory biomarkers. Conclusion: This study suggests that the BChE activity reduction might serve as an early indicator of acute systemic inflammation. Furthermore, BChE activity, measured using a POCT system, might play an important role in the early diagnosis of the trauma-induced systemic inflammation. Keywords: trauma, injury, early diagnostics, cholinergic, pseudocholinesterase, SIRS

  18. Tensile mechanical response of polyethylene – clay nanocomposites.

    Directory of Open Access Journals (Sweden)

    2007-03-01

    Full Text Available In this work we report on the microstructural and the mechanical characteristics of high density polyethylene (HDPE-clay nanocomposites, with particular attention to the creep behaviour. The samples were prepared through melt compounding, using two high-density polyethylenes with different melt flow rate (MFR, two different organo-modified clays, and changing the relative amount of a polyethylene grafted with maleic anhydride (PEgMA compatibilizer. The intercalation process is more effective as the matrix melt viscosity decreases (higher MFR, while the clay interlamellar spacing increases as the compatibilizer amount increases. The relative stiffness of the nanocomposites increases with the addition of clay, with a limited enhancement of the relative yield stress. The better intercalation obtained by the addition of the compatibilizer is not accompanied by a concurrent improvement of the tensile mechanical properties. The creep resistance is enhanced by the introduction of clay, with an appreciable dependence on both the polyethylene and the clay type.

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

    International Nuclear Information System (INIS)

    Plannerer, H.N.

    1997-01-01

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

  20. Fluid mechanical responses to nutrient depletion in fungi and biofilmsa)

    Science.gov (United States)

    Brenner, Michael P.

    2014-10-01

    In both fungi and bacterial biofilms, when nutrients are depleted, the organisms cannot physically migrate to find a new source, but instead must develop adaptations that allow them to survive. This paper reviews our work attempting to discover design principles for these adaptations. We develop fluid mechanical models, and aim to understand whether these suggest organizing principles for the observed morphological diversity. Determining whether a proposed organizing principle explains extant biological designs is fraught with difficulty: simply because a design principle predicts characteristics similar to an organism's morphology could just as well be accidental as revealing. In each of the two sets of examples, we adopt different strategies to develop understanding in spite of this difficulty. Within the fungal phylum Ascomycota, we use the large observed diversity of different morphological solutions to the fundamental fluid mechanical problem to measure how far each solution is from a design optimum, thereby measuring how far the extant designs deviate from the hypothesized optimum. This allows comparing different design principles to each other. For biofilms, we use engineering principles to make qualitative predictions of what types of adaptations might exist given the physicochemical properties of the repertoire of proteins that bacteria can create, and then find evidence for these adaptations in experiments. While on the surface this paper addresses the particular adaptations used by the fungal phylum Ascomycota and bacterial biofilms, we also aim to motivate discussion of different approaches to using design principles, fluid mechanical or otherwise, to rationalize observed engineering solutions in biology.

  1. Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

    Science.gov (United States)

    Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

    2017-01-01

    Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

  2. Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

    Science.gov (United States)

    Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

    2017-01-01

    Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

  3. Early systemic bacterial dissemination and a rapid innate immune response characterize genetic resistance to plague of SEG mice.

    Science.gov (United States)

    Demeure, Christian E; Blanchet, Charlène; Fitting, Catherine; Fayolle, Corinne; Khun, Huot; Szatanik, Marek; Milon, Geneviève; Panthier, Jean-Jacques; Jaubert, Jean; Montagutelli, Xavier; Huerre, Michel; Cavaillon, Jean-Marc; Carniel, Elisabeth

    2012-01-01

    Although laboratory mice are usually highly susceptible to Yersinia pestis, we recently identified a mouse strain (SEG) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance. The kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in SEG and susceptible C57BL/6J mice after subcutaneous infection with the virulent Y. pestis CO92. Bacterial invasion occurred early (day 2) but was transient in SEG/Pas mice, whereas in C57BL/6J mice it was delayed but continuous until death. The bacterial load in all organs significantly correlated with the production of 5 cytokines (granulocyte colony-stimulating factor, keratinocyte-derived chemokine (KC), macrophage cationic peptide-1 (MCP-1), interleukin 1α, and interleukin 6) involved in monocyte and neutrophil recruitment. Indeed, higher proportions of these 2 cell types in blood and massive recruitment of F4/80(+)CD11b(-) macrophages in the spleen were observed in SEG/Pas mice at an early time point (day 2). Later times after infection (day 4) were characterized in C57BL/6J mice by destructive lesions of the spleen and impaired granulopoiesis. A fast and efficient Y. pestis dissemination in SEG mice may be critical for the triggering of an early and effective innate immune response necessary for surviving plague.

  4. Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

    Science.gov (United States)

    Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

    2010-11-01

    In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

  5. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  6. Taking responsibility for the early assessment and treatment of patients with musculoskeletal pain

    DEFF Research Database (Denmark)

    Foster, Nadine E; Hartvigsen, Jan; Croft, Peter R

    2012-01-01

    ABSTRACT: Musculoskeletal pain is common across all populations and costly in terms of impact on the individual and, more generally, on society. In most health-care systems, the first person to see the patient with a musculoskeletal problem such as back pain is the general practitioner, and acces......, and underpinning evidence, for reconsidering who should take responsibility for the early assessment and treatment of patients with musculoskeletal problems....

  7. Strengthening Laboratory Capacity for Early Warning Alert and Response System (EWARS) in Indonesia

    OpenAIRE

    Kandel, Nirmal; Hapsari, Ratna Budi; Riana, Dyah Armi; Setiawaty, Vivi; Larasati, Wita; Wulandari, Endang; Purwanto, Edy

    2017-01-01

    Background: Establishment of Early Warning Alert and Response System (EWARS) in Indonesia was initiated since 2009 in few selected provinces and government was planning to roll out in other provinces. Before initiating this roll out the assessment of performance of EWARS in 2012 was conducted. The aim of the assessment is to strengthen laboratory for supporting to EWARS for alerts testing. Methods: Laboratory capacity mapping tool and laboratory algorithm for twenty two priority diseases of ...

  8. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

  9. SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection

    DEFF Research Database (Denmark)

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin

    2013-01-01

    , and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its...... viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host...

  10. DNA Damage Response and Immune Defence: Links and Mechanisms

    Directory of Open Access Journals (Sweden)

    Björn Schumacher

    2016-08-01

    Full Text Available DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i which molecular and cellular pathways of DDR activate immune signalling, (ii how DNA damage drives chronic inflammation, and (iii how chronic inflammation causes DNA damage and pathology in humans.

  11. Piezoelectric Response of Ferroelectric Ceramics Under Mechanical Stress

    Science.gov (United States)

    2015-09-17

    response of the bulk Barium Titanate-based dielectric in such capacitors has not yet been addressed for shocks above 3,000 g. Thus, the current research...3.15 Low Voltage Capacitor Dielectric Volume Sections . . . . . . . . . . . . . . . 81 3.16 Electrodes, Terminals and Boundary Condition Surfaces...Final Separation from the Flexing Board of 1812 Capacitor after 36-inch Drop . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 4.21 Dielectric

  12. Semantic mechanisms may be responsible for developing synesthesia

    Directory of Open Access Journals (Sweden)

    Aleksandra eMroczko-Wąsowicz

    2014-08-01

    Full Text Available Currently, little is known about how synesthesia develops and which aspects of synesthesia can be acquired through a learning process. We review the increasing evidence for the role of semantic representations in the induction of synesthesia, and argue for the thesis that synesthetic abilities are developed and modified by semantic mechanisms. That is, in certain people semantic mechanisms associate concepts with perception-like experiences—and this association occurs in an extraordinary way. This phenomenon can be referred to as higher synesthesia or ideasthesia. The present analysis suggests that synesthesia develops during childhood and is being enriched further throughout the synesthetes’ lifetime; for example, the already existing concurrents may be adopted by novel inducers or new concurrents may be formed. For a deeper understanding of the origin and nature of synesthesia we propose to focus future research on two aspects: i the similarities between synesthesia and ordinary phenomenal experiences based on concepts, and ii the tight entanglement of perception, cognition and the conceptualization of the world. Most importantly, an explanation of how biological systems get to generate experiences, synesthetic or not, may have to involve an explanation of how we form semantic networks in general and what their role is in our ability to be aware of the surrounding world.

  13. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    Directory of Open Access Journals (Sweden)

    Eneour Puill-Stephan

    Full Text Available Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals.Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR. Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria during winnowing processes as symbioses are fine-tuned.Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are

  14. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    Science.gov (United States)

    Puill-Stephan, Eneour; Seneca, François O; Miller, David J; van Oppen, Madeleine J H; Willis, Bette L

    2012-01-01

    Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are needed to further

  15. Mechanical response of spiral interconnect arrays for highly stretchable electronics

    KAUST Repository

    Qaiser, Nadeem

    2017-11-21

    A spiral interconnect array is a commonly used architecture for stretchable electronics, which accommodates large deformations during stretching. Here, we show the effect of different geometrical morphologies on the deformation behavior of the spiral island network. We use numerical modeling to calculate the stresses and strains in the spiral interconnects under the prescribed displacement of 1000 μm. Our result shows that spiral arm elongation depends on the angular position of that particular spiral in the array. We also introduce the concept of a unit-cell, which fairly replicates the deformation mechanism for full complex hexagon, diamond, and square shaped arrays. The spiral interconnects which are axially connected between displaced and fixed islands attain higher stretchability and thus experience the maximum deformations. We perform tensile testing of 3D printed replica and find that experimental observations corroborate with theoretical study.

  16. Mechanical response of spiral interconnect arrays for highly stretchable electronics

    KAUST Repository

    Qaiser, Nadeem; Khan, S. M.; Nour, Maha A.; Rehman, M. U.; Rojas, J. P.; Hussain, Muhammad Mustafa

    2017-01-01

    A spiral interconnect array is a commonly used architecture for stretchable electronics, which accommodates large deformations during stretching. Here, we show the effect of different geometrical morphologies on the deformation behavior of the spiral island network. We use numerical modeling to calculate the stresses and strains in the spiral interconnects under the prescribed displacement of 1000 μm. Our result shows that spiral arm elongation depends on the angular position of that particular spiral in the array. We also introduce the concept of a unit-cell, which fairly replicates the deformation mechanism for full complex hexagon, diamond, and square shaped arrays. The spiral interconnects which are axially connected between displaced and fixed islands attain higher stretchability and thus experience the maximum deformations. We perform tensile testing of 3D printed replica and find that experimental observations corroborate with theoretical study.

  17. Early Career Boot Camp: a novel mechanism for enhancing early career development for psychologists in academic healthcare.

    Science.gov (United States)

    Foran-Tuller, Kelly; Robiner, William N; Breland-Noble, Alfiee; Otey-Scott, Stacie; Wryobeck, John; King, Cheryl; Sanders, Kathryn

    2012-03-01

    The purpose of this article is to describe a pilot mentoring program for Early Career Psychologists (ECPs) working in Academic Health Centers (AHCs) and synthesize the lessons learned to contribute to future ECP and AHC career development training programs. The authors describe an early career development model, named the Early Career Boot Camp. This intensive experience was conducted as a workshop meant to build a supportive network and to provide mentorship and survival tools for working in AHCs. Four major components were addressed: professional effectiveness, clinical supervision, strategic career planning, and academic research. Nineteen attendees who were currently less than 5 years post completion of doctoral graduate programs in psychology participated in the program. The majority of boot camp components were rated as good to excellent, with no component receiving below average ratings. Of the components offered within the boot camp, mentoring and research activities were rated the strongest, followed by educational activities, challenges in AHCS, and promotion and tenure. The article describes the purpose, development, implementation, and assessment of the program in detail in an effort to provide an established outline for future organizations to utilize when mentoring ECPs.

  18. Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator-score and its value in the Rapid Response System.

    Science.gov (United States)

    Douw, Gooske; Huisman-de Waal, Getty; van Zanten, Arthur R H; van der Hoeven, Johannes G; Schoonhoven, Lisette

    2017-09-01

    To determine the predictive value of individual and combined dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score levels, differentiating between Early Warning Scores reaching the trigger threshold to call a rapid response team and Early Warning Score levels not reaching this point. Dutch-early-nurse-worry-indicator-score comprises nine indicators underlying nurses' 'worry' about a patient's condition. All indicators independently show significant association with unplanned intensive care/high dependency unit admission or unexpected mortality. Prediction of this outcome improved by adding the dutch-early-nurse-worry-indicator-score indicators to an Early Warning Score based on vital signs. An observational cohort study was conducted on three surgical wards in a tertiary university-affiliated teaching hospital. Included were surgical, native-speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early-nurse-worry-indicator-score indicators every shift or when worried. Vital signs were measured according to the prevailing protocol. Unplanned intensive care/high dependency unit admission or unexpected mortality was the composite endpoint. Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators were calculated at various Early Warning Score levels in control and event groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a multiple logistic regression analysis, we calculated a weighted score and calculated sensitivity, specificity, positive predicted value and negative predicted value for each possible total score. In 3522 patients, 102 (2·9%) had an unplanned intensive care/high dependency unit admissions (n = 97) or unexpected mortality (n = 5). Patients with such events and only slightly changed vital signs had significantly higher percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators expressed than patients in the control group. Increasing number

  19. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    Science.gov (United States)

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

  20. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

    Science.gov (United States)

    Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2015-07-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

  1. Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

    Science.gov (United States)

    Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

    2014-01-01

    Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

  2. Phosphorene under strain:electronic, mechanical and piezoelectric responses

    Science.gov (United States)

    Drissi, L. B.; Sadki, S.; Sadki, K.

    2018-01-01

    Structural, electronic, elastic and piezoelectric properties of pure phosphorene under in-plane strain are investigated using first-principles calculations based on density functional theory. The two critical yielding points are determined along armchair and zigzag directions. It is shown that the buckling, the band gap and the charge transfer can be controlled under strains. A semiconductor to metallic transition is observed in metastable region. Polar plots of Young's modulus, Poisson ratio, sound velocities and Debye temperature exhibit evident anisotropic feature of phosphorene and indicate auxetic behavior for some angles θ. Our calculations show also that phosphorene has both in-plane and out-of-plane piezoelectric responses comparable to known 2D materials. The findings of this work reveal the great potential of pure phosphorene in nanomechanical applications.

  3. Sugar consumption produces effects similar to early life stress exposure on hippocampal markers of neurogenesis and stress response

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2016-01-01

    Full Text Available Adverse early life experience is a known risk factor for psychiatric disorders. It is also known that stress influences food preference. We were interested in exploring whether the choice of diet following early life stress exerts long-lasting molecular changes in the brain, particularly the hippocampus, a region critically involved in stress regulation and behavioural outcomes. Here, we examined the impact of early life stress induced by limited nesting material (LN and chronic sucrose availability post-weaning on an array of hippocampal genes related to plasticity, neurogenesis, stress and inflammatory responses and mitochondrial biogenesis. To examine mechanisms underlying the impact of LN and sugar intake on hippocampal gene expression, we investigated the role of DNA methylation. As females are more likely to experience adverse life events, we studied female Sprague-Dawley rats. After mating LN was imposed from days 2-9 postpartum. From 3-15 weeks of age, female Control and LN siblings had unlimited to access to either chow and water, or chow, water and 25% sucrose solution. LN markedly reduced glucocorticoid receptor (GR and neurogenic differentiation 1 (Neurod1 mRNA, markers involved in stress and hippocampal plasticity respectively, by more than 40%, with a similar effect of sugar intake in control rats. However, no further impact was observed in LN rats consuming sugar. Hippocampal Akt3 mRNA expression was similarly affected by LN and sucrose consumption. Interestingly, DNA methylation across 4 CpG sites of the GR and Neurod1 promoters was similar in LN and control rats. In summary, early life stress and post-weaning sugar intake produced long-term effects on hippocampal GR and Neurod1 expression. Moreover we found no evidence of altered promoter DNA methylation. We demonstrate for the first time that chronic sucrose consumption alone produces similar detrimental effects on the expression of hippocampal genes as LN exposure.

  4. Early print-tuned ERP response with minimal involvement of linguistic processing in Japanese Hiragana strings.

    Science.gov (United States)

    Okumura, Yasuko; Kasai, Tetsuko; Murohashi, Harumitsu

    2014-04-16

    The act of reading leads to the development of specific neural responses for print, the most frequently reported of which is the left occipitotemporal N170 component of event-related potentials. However, it remains unclear whether this electrophysiological response solely involves print-tuned neural activities. The present study examined an early print-tuned event-related potential response with minimal involvement of linguistic processing in a nonalphabetic language. Japanese Hiragana words, nonwords, and alphanumeric symbol strings were presented rapidly and the task was to detect the change in color of a fixation cross to restrict linguistic processing. As a result, Hiragana words and nonwords elicited a larger posterior N1 than alphanumeric symbol strings bilaterally, irrespective of intercharacter spacing. The fact that this N1 was enhanced specifically for rapidly presented Hiragana strings suggests the existence of print-tuned neural processes that are relatively independent of the influence of linguistic processing.

  5. Hydro-thermo-mechanical response of a fractured rock block

    International Nuclear Information System (INIS)

    Kelkar, S.; Zyvoloski, G.

    1990-01-01

    Hydro-thermo-mechanical effects in fractured rocks are important in many engineering applications and geophysical processes. Modeling these effects is made difficult by the fact that the governing equations are nonlinear and coupled, and the problems to be solved are three dimensional. In this paper we describe a numerical code developed for this purpose. The code is finite element based to allow for complicated geometries, and the time differencing is implicit, allowing for large time steps. The use of state-of-the-art equation solvers has resulted in a practical code. The code is capable of fully three dimensional simulations, however, in this paper we consider only the case of two dimensional heat and mass flow coupled to one dimensional deformation. Partial verification of the code is obtained by comparison with published semianalytical results. Several examples are presented to demonstrate the effects of matrix expansion, due to pore pressure and heating, on fracture opening due to fluid injection. 16 refs., 11 figs

  6. Molecular mechanisms of responses to radiation through protein kinase C

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo

    2005-01-01

    Described are the activation and cascade of the protein kinase C (PKC) which mediating the control of radiation-induced apoptosis. PKC is a family of c-, n- and a-subtypes and plays a major role in responding to the radiation exposure for DNA repair, cell cycle arrest and apoptosis. The author has conducted studies of mouse thymic lymphoma cells which have a property to respond even to low dose radiation, and has showed that, in the highly radiosensitive cell strain, 3SBH5 where apoptosis occurs in 50 and 90% post 0.5 and 2 Gy exposure, respectively, cPKC works as a surviving signal without intracellular movement after irradiation. In contrast, PKC has been alternatively shown to participate in apoptosis induction, showing that different enzyme species in the subtypes work specifically depending on passing time. Comparison with the radio-resistant cell strain, XR223, has revealed that the difference in the localization controls of PKCδ in the cell determines the radiosensitivity, however, the control mechanism is found to be separate from Atm pathway by which PKCδ is usually regulated. Recent studies have revealed that PKC performs the intracellular cross-talk in various phosphorylation cascades. Studies of PKC can be toward their uses for radiation effect assessment, radiotherapy and medicare for urgent exposure. (S.I.)

  7. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    Science.gov (United States)

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  8. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    Science.gov (United States)

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

  9. Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways.

    Directory of Open Access Journals (Sweden)

    Stephanie M Rainey

    2016-04-01

    Full Text Available The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus. Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3' open reading frame than the 5' non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia's antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to

  10. The stress response to surgery: release mechanisms and the modifying effect of pain relief

    DEFF Research Database (Denmark)

    Kehlet, H

    1989-01-01

    This short review updates information on the release mechanisms of the systemic response to surgical injury and the modifying effect of pain relief. Initiation of the response is primarily due to afferent nerve impulses combined with release of humoral substances (such as prostaglandins, kinins...... in releasing the classical endocrine catabolic response, while humoral factors are important for the hyperthermic response, changes in coagulation and fibrinolysis immunofunction, and capillary permeability. The modifying effect of pain relief on the surgical stress response is dependent upon the technique...... on the stress response. In summary, pain alleviation itself may not necessarily lead to an important modification of the stress response, and a combined approach with inhibition of the neural and humoral release mechanisms is necessary for a pronounced inhibition or prevention of the response to surgical injury....

  11. Energy input and response from prompt and early optical afterglow emission in gamma-ray bursts.

    Science.gov (United States)

    Vestrand, W T; Wren, J A; Wozniak, P R; Aptekar, R; Golentskii, S; Pal'shin, V; Sakamoto, T; White, R R; Evans, S; Casperson, D; Fenimore, E

    2006-07-13

    The taxonomy of optical emission detected during the critical first few minutes after the onset of a gamma-ray burst (GRB) defines two broad classes: prompt optical emission correlated with prompt gamma-ray emission, and early optical afterglow emission uncorrelated with the gamma-ray emission. The standard theoretical interpretation attributes prompt emission to internal shocks in the ultra-relativistic outflow generated by the internal engine; early afterglow emission is attributed to shocks generated by interaction with the surrounding medium. Here we report on observations of a bright GRB that, for the first time, clearly show the temporal relationship and relative strength of the two optical components. The observations indicate that early afterglow emission can be understood as reverberation of the energy input measured by prompt emission. Measurements of the early afterglow reverberations therefore probe the structure of the environment around the burst, whereas the subsequent response to late-time impulsive energy releases reveals how earlier flaring episodes have altered the jet and environment parameters. Many GRBs are generated by the death of massive stars that were born and died before the Universe was ten per cent of its current age, so GRB afterglow reverberations provide clues about the environments around some of the first stars.

  12. Recognition of Immune Response for the Early Diagnosis and Treatment of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Adrese M. Kandahari

    2015-01-01

    Full Text Available Osteoarthritis is a common and debilitating joint disease that affects up to 30 million Americans, leading to significant disability, reduction in quality of life, and costing the United States tens of billions of dollars annually. Classically, osteoarthritis has been characterized as a degenerative, wear-and-tear disease, but recent research has identified it as an immunopathological disease on a spectrum between healthy condition and rheumatoid arthritis. A systematic literature review demonstrates that the disease pathogenesis is driven by an early innate immune response which progressively catalyzes degenerative changes that ultimately lead to an altered joint microenvironment. It is feasible to detect this infiltration of cells in the early, and presumably asymptomatic, phase of the disease through noninvasive imaging techniques. This screening can serve to aid clinicians in potentially identifying high-risk patients, hopefully leading to early effective management, vast improvements in quality of life, and significant reductions in disability, morbidity, and cost related to osteoarthritis. Although the diagnosis and treatment of osteoarthritis routinely utilize both invasive and non-invasive strategies, imaging techniques specific to inflammatory cells are not commonly employed for these purposes. This review discusses this paradigm and aims to shift the focus of future osteoarthritis-related research towards early diagnosis of the disease process.

  13. The Vallecas Project: a cohort to identify early markers and mechanisms of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Javier eOlazarán

    2015-09-01

    Full Text Available Introduction. Alzheimer’s disease (AD is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects. Methods. We launched the Vallecas Project (VP, a cohort study of non-demented people aged 70 to 85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods. Results. A total of 1,169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9, 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E (APOE gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI. Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging (MRI study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for four years after the baseline. Conclusion. We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

  14. Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

    Science.gov (United States)

    Nusaibah, S A; Siti Nor Akmar, A; Idris, A S; Sariah, M; Mohamad Pauzi, Z

    2016-12-01

    Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Mechanisms governing the responses to anthracnose pathogen in Juglans spp.

    Science.gov (United States)

    Pollegioni, P; Van der Linden, G; Belisario, A; Gras, M; Anselmi, N; Olimpieri, I; Luongo, L; Santini, A; Turco, E; Scarascia Mugnozza, G; Malvolti, M E

    2012-06-30

    Juglans nigra and Juglans regia are two highly economically important species for wood and fruit production that are susceptible to anthracnose caused by Gnomonia leptostyla. The identification of genotypes resistant to anthracnose could represent a valid alternative to agronomic and chemical management. In this study, we analyzed 72 walnut genotypes that showed a variety of resistance phenotypes in response to natural infection. According to the disease severity rating and microsatellite fingerprinting analysis, these genotypes were divided into three main groups: (40) J. nigra resistant, (1) J. nigra susceptible, and (31) J. regia susceptible. Data on leaf emergence rates and analysis of in vivo pathogenicity indicated that the incidence of anthracnose disease in the field might be partially conditioned by two key factors: the age and/or availability of susceptible leaves during the primary infection of fungus (avoidance by late flushing) and partial host resistance. NBS profiling approach, based on PCR amplification with an adapter primer for an adapter matching a restriction enzyme site and a degenerate primer targeting the conserved motifs present in the NBS domain of NBS-LRR genes, was applied. The results revealed the presence of a candidate marker that correlated to a reduction in anthracnose incidence in 72 walnut genotypes. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Responsive parenting: establishing early foundations for social, communication, and independent problem-solving skills.

    Science.gov (United States)

    Landry, Susan H; Smith, Karen E; Swank, Paul R

    2006-07-01

    Mothers whose infants varied in early biological characteristics (born at term, n = 120; born at very low birth weight [VLBW], n = 144) were randomized to a target group (n = 133) or developmental feedback comparison group (n = 131) to determine whether learning responsive behaviors would facilitate infant development. The target condition included videotaped examples, problem-solving activities, and mothers' critique of their own behaviors through video procedures across 10 home visits. All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessments conducted across 6-13 months of age; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW. Increased maternal responsiveness facilitated greater growth in target infants' social, emotional, communication, and cognitive competence, supporting a causal role for responsiveness on infant development. Although benefits were generally comparable across risk groups, aspects of social and emotional skills showed greater change for those born at VLBW. Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains.

  17. Structural changes in the German pharmaceutical market: price setting mechanisms based on the early benefit evaluation.

    Science.gov (United States)

    Henschke, Cornelia; Sundmacher, Leonie; Busse, Reinhard

    2013-03-01

    In the past, free price setting mechanisms in Germany led to high prices of patented pharmaceuticals and to increasing expenditures in the pharmaceutical sector. In order to control patented pharmaceutical prices and to curb increasing pharmaceutical spending, the Act for Restructuring the Pharmaceutical Market in Statutory Health Insurance (AMNOG) came into effect on 1st January 2011. In a structured dossier, pharmaceutical manufacturers have to demonstrate the additional therapeutic benefit of the newly approved pharmaceutical compared to its appropriate comparator. According to the level of additional benefit, pharmaceuticals will be subject to price negotiations between the Federal Association of Statutory Health Insurance Funds and the pharmaceutical company concerned (or assigned to a reference price group in case of no additional benefit). Therefore, the health care reform is a first step to decision making based on "value for money". The process of price setting based on early benefit evaluation has an impact on the German as well as the European pharmaceutical markets. Therefore, these structural changes in Germany are of importance for pricing decisions in many European countries both from a political point of view and for strategic planning for pharmaceutical manufacturers, which may have an effect on insured patients' access to pharmaceuticals. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation.

    Science.gov (United States)

    Voga, Gorazd

    2012-07-06

    Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning.

  19. Mechanisms Underlying the Association Between Early-Life Adversity and Physical Health: Charting a Course for the Future.

    Science.gov (United States)

    Bush, Nicole R; Lane, Richard D; McLaughlin, Katie A

    Early-life adversities (ELA) are associated with subsequent pervasive alterations across a wide range of neurobiological systems and psychosocial factors that contribute to accelerated onset of health problems and diseases. In this article, we provide an integrated perspective on recent developments in research on ELA, based on the articles published in this Special Issue of Psychosomatic Medicine. We focus on the following: 1) the distinction between specific versus general aspects of ELA with regard to the nature of exposure (e.g., physical and sexual abuse, emotional abuse or neglect, relative socioeconomic deprivation), biological and behavioral correlates of ELA, and differences across diseases; 2) the importance of timing in the critical phases of exposure to ELA; and 3) adaptive versus dysfunctional responses to ELA and their consequences for biological and behavioral risk factors for adverse health outcomes. This article concludes with outlining important new targets for research in this area, including the neurobiology of affect as a mechanism linking ELA to adverse health outcomes, and the need for large-scale longitudinal investigations of multisystem processes relevant to ELA in diverse samples, starting prenatally, continuing to late adolescence, and with long-term follow-up assessments that enable evaluation of incident disease outcomes.

  20. Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network.

    Science.gov (United States)

    Cordes, Kristina M; Cookson, Susan T; Boyd, Andrew T; Hardy, Colleen; Malik, Mamunur Rahman; Mala, Peter; El Tahir, Khalid; Everard, Marthe; Jasiem, Mohamad; Husain, Farah

    2017-11-01

    Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security.

  1. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    International Nuclear Information System (INIS)

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin

    2006-01-01

    Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor β immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent

  2. Impaired early visual response modulations to spatial information in chronic schizophrenia

    Science.gov (United States)

    Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

    2011-01-01

    Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

  3. Developmental changes in mismatch responses to mandarin consonants and lexical tones from early to middle childhood.

    Directory of Open Access Journals (Sweden)

    Huei-Mei Liu

    Full Text Available The purpose of this study was to use mismatch responses (MMRs to explore the dynamic changes of Mandarin speech perception abilities from early to middle childhood. Twenty preschoolers, 18 school-aged children, and 26 adults participated in this study. Two sets of synthesized speech stimuli varying in Mandarin consonant (alveolo-palatal affricate vs. fricative and lexical tone features (rising vs. contour tone were used to examine the developmental course of speech perception abilities. The results indicated that only the adult group demonstrated typical early mismatch negativity (MMN responses, suggesting that the ability to discriminate specific speech cues in Mandarin consonant and lexical tone is a continuing process in preschool- and school-aged children. Additionally, distinct MMR patterns provided evidence indicating diverse developmental courses to different speech characteristics. By incorporating data from the two speech conditions, we propose using MMR profiles consisting of mismatch negativity (MMN, positive mismatch response (p-MMR, and late discriminative negativity (LDN as possible brain indices to investigate speech perception development.

  4. FDG PET/CT in initial staging and early response to chemotherapy assessment of paediatric rhabdomyosarcomas

    International Nuclear Information System (INIS)

    Eugene, T.; Ansquer, C.; Oudoux, A.; Carlier, T.; Kraeber-Bodere, T.; Bodet-Milin, C.; Corradini, N.; Thomas, C.; Dupas, B.

    2010-01-01

    Purpose: The objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma. Patients and methods: Prior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years). Results: PET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years). Conclusion: This study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment. (authors)

  5. The p66(Shc adaptor protein controls oxidative stress response in early bovine embryos.

    Directory of Open Access Journals (Sweden)

    Dean H Betts

    Full Text Available The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2-4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2-4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.

  6. Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection

    Directory of Open Access Journals (Sweden)

    Yiming Wang

    2014-12-01

    Full Text Available Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L. in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10 by RT-PCR, and phytoalexins (sakuranetin and momilactone A with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05 in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.

  7. Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET.

    Science.gov (United States)

    Guo, Ning; Zhang, Fan; Zhang, Xiaomeng; Guo, Jinxia; Lang, Lixin; Kiesewetter, Dale O; Niu, Gang; Li, Quanzheng; Chen, Xiaoyuan

    2015-12-01

    The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF121/recombinant toxin gelonin (rGel) using dynamic [(18)F]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [(18)F]FPPRGD2 that targets to integrin αvβ3 were performed at days 0 (baseline), 1, and 3 since VEGF121/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF121/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p dynamic PET with [(18)F]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF121/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET.

  8. Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Lee SH

    2015-04-01

    in AFP responders than in non-responders (72.1% vs 47.0%, respectively; P=0.007. In a sub-group with SD, OS (median 12.7 vs 5.8 months, respectively and PFS (median 9.1 vs 3.7 months, respectively were significantly longer in AFP responders than in non-responders (all P<0.05. Conclusion: Early AFP response may be useful for predicting survival in patients with advanced HCC treated with sorafenib. Keywords: α-fetoprotein, hepatocellular carcinoma, response, prognosis, treatment outcome, sorafenib

  9. [Dose-response relationship of ropivacaine for epidural block in early herpes zoster guided by CT].

    Science.gov (United States)

    Xie, K Y; Ma, J B; Xu, Q; Huang, B; Yao, M; Ni, H D; Deng, J J; Chen, G D

    2017-12-26

    Objective: To determine the dose-response relationship of ropivacaine for epidural block in early herpes zoster by CT guided. Methods: From January 2015 to February 2017, according to the principle of completely random digital table, 80 patients with early herpes zoster who were prepared for epidural block were divided into 4 groups(each group 20 patients): in group A the concentration of ropivacaine was 0.08%, in group B was 0.10%, in group C was 0.12% and in group D was 0.14%.Under CT guidance, epidural puncture was performed in the relevant section, mixing liquid 5.0 ml (with 10% iodohydrin)were injected into epidural gap.CT scan showed that the mixing liquid covered the relevant spinal nerve segmental.The numeric rating scale(NRS) values before treatment and at 30 minutes, the incidence of adverse reactions were recorded, and the treatment were evaluated. The response to ropivacaine for epidural block in early herpes zoster was defined as positive when the NRS values was less than or equal to one.The ED(50), ED(95) and 95% confidence interval ( CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were calculated by probit analysis. Results: The NRS values before treatment were 5.00(4.00, 6.00), 5.00(4.25, 6.00), 5.50(5.00, 6.00) and 5.00(4.00, 6.00), the difference was no significant( Z =2.576, P =0.462). The NRS values at 30 minutes decreased and the effective rate of the treatment increased(χ(2)=8.371, P =0.004), following ropivacaine dose gradient increasing, they were 1.50(1.00, 2.00), 1.00(1.00, 2.00), 0.50(0.00, 1.00) and 0.00(0.00, 1.00), the difference was statistically significant ( Z =17.421, P =0.001). There was one case in group C and four cases in group D were hypoesthesia, others were no significant adverse reactions occurred. The ED(50) and ED(95) (95% CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were 0.078%(0.015%-0.095%)and 0.157%(0.133%-0.271%), respectively. Conclusion: Ropivacaine for

  10. A gene expression profile indicative of early stage HER2 targeted therapy response.

    Science.gov (United States)

    O'Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O'Connor, Robert

    2013-07-01

    Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.

  11. Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions.

    Science.gov (United States)

    Loranger, Hannah; Zotz, Gerhard; Bader, Maaike Y

    2016-01-01

    On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua, Picea abies, Pinus cembra, Pinus uncinata and Sorbus aucuparia In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics. © The Authors 2016. Published by Oxford University Press on behalf of the Annals of Botany Company.

  12. Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

    NARCIS (Netherlands)

    Denning, Denise; Roos, Wouter H

    2016-01-01

    The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

  13. Early 24-hour blood pressure response to Roux-en-Y gastric bypass in obese patients

    DEFF Research Database (Denmark)

    Pedersen, Julie S; Borup, Christian; Damgaard, Morten

    2017-01-01

    Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after 'malabsorptive' surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass...... (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean...

  14. Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis Express Increased Inflammatory Responses After Antimony Therapy.

    Science.gov (United States)

    Costa, Rúbia S; Carvalho, Lucas P; Campos, Taís M; Magalhães, Andréa S; Passos, Sara T; Schriefer, Albert; Silva, Juliana A; Lago, Ednaldo; Paixão, Camilla S; Machado, Paulo; Scott, Phillip; Carvalho, Edgar M

    2018-02-14

    Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure. A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects. A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  15. A nationwide web-based automated system for early outbreak detection and rapid response in China

    Directory of Open Access Journals (Sweden)

    Yilan Liao

    2011-03-01

    Full Text Available Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and to transmit that information either in real-time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.

  16. The microtubule associated protein END BINDING 1 represses root responses to mechanical cues.

    Science.gov (United States)

    Gleeson, Laura; Squires, Shannon; Bisgrove, Sherryl R

    2012-05-01

    The ability of roots to navigate around rocks and other debris as they grow through the soil requires a mechanism for detecting and responding to input from both touch and gravity sensing systems. The microtubule associated protein END BINDING 1b (EB1b) is involved in this process as mutants have defects responding to combinations of touch and gravity cues. This study investigates the role of EB1b in root responses to mechanical cues. We find that eb1b-1 mutant roots exhibit an increase over wild type in their response to touch and that the expression of EB1b genes in transgenic mutants restores the response to wild type levels, indicating that EB1b is an inhibitor of the response. Mutant roots are also hypersensitive to increased levels of mechanical stimulation, revealing the presence of another process that activates the response. These findings are supported by analyses of double mutants between eb1b-1 and seedlings carrying mutations in PHOSPHOGLUCOMUTASE (PGM), ALTERED RESPONSE TO GRAVITY1 (ARG1), or TOUCH3 (TCH3), genes that encode proteins involved in gravity sensing, signaling, or touch responses, respectively. A model is proposed in which root responses to mechanical cues are modulated by at least two competing regulatory processes, one that promotes touch-mediated growth and another, regulated by EB1b, which dampens root responses to touch and enhances gravitropism. © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Humidity Responsive Photonic Sensor based on a Carboxymethyl Cellulose Mechanical Actuator

    OpenAIRE

    Hartings, Matthew; Douglass, Kevin O.; Neice, Claire; Ahmed, Zeeshan

    2017-01-01

    We describe an intuitive and simple method for exploiting humidity-driven volume changes in carboxymethyl cellulose (CMC) to fabricate a humidity responsive actuator on a glass fiber substrate. We optimize this platform to generate a photonic-based humidity sensor where CMC coated on a fiber optic containing a fiber Bragg grating (FBG) actuates a mechanical strain in response to humidity changes. The humidity-driven mechanical deformation of the FBG results in a large lin...

  18. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  19. Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

    Science.gov (United States)

    Tosi, F; Moghetti, P; Castello, R; Negri, C; Bonora, E; Muggeo, M

    1996-08-01

    The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

  20. Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood.

    Science.gov (United States)

    Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H

    2016-01-01

    Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning. © 2014 Society for the Study of Addiction.

  1. Ekman pumping mechanism driving precipitation anomalies in response to equatorial heating

    Science.gov (United States)

    Hamouda, Mostafa E.; Kucharski, Fred

    2018-03-01

    In this paper some basic mechanisms for rainfall teleconnections to a localized tropical sea surface temperature anomaly are re-visited using idealized AGCM aqua-planet simulations. The dynamical response is generally in good agreement with the Gill-Matsuno theory. The mechanisms analyzed are (1) the stabilization of the tropical troposphere outside the heating region, (2) the Walker circulation modification and (3) Ekman pumping induced by the low-level circulation responses. It is demonstrated that all three mechanisms, and in particular (2) and (3), contribute to the remote rainfall teleconnections. However, mechanism (3) best coincides with the overall horizontal structure of rainfall responses. It is shown by using the models boundary layer parameterization that low-level vertical velocities are indeed caused by Ekman pumping and that this induces vertical velocities in the whole tropospheric column through convective feedbacks. Also the modification of the responses due to the presence of idealized warm pools is investigated. It is shown that warm pools modify the speed of the tropical waves, consistent with Doppler shifts and are thus able to modify the Walker circulation adjustments and remote rainfall responses. The sensitivity of the responses, and in particular the importance of the Ekman pumping mechanism, to large variations in the drag coefficient is also tested, and it is shown that the Ekman pumping mechanism is robust for a wide range of values.

  2. Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage.

    Science.gov (United States)

    Milo, Scarlet; Acosta, Florianne B; Hathaway, Hollie J; Wallace, Laura A; Thet, Naing T; Jenkins, A Toby A

    2018-03-23

    Formation of crystalline biofilms following infection by Proteus mirabilis can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric "lozenge", able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease. Sensor performance was evaluated within a laboratory model of the catheterized urinary tract, infected with both urease positive and negative bacterial strains under conditions of established infection, achieving an average "early warning" of catheter blockage of 14.5 h. Signaling only occurred following infection with urease positive bacteria. Translation of these sensors into a clinical environment would allow appropriate intervention before the occurrence of catheter blockage, a problem for which there is currently no effective control method.

  3. Characterization of the early local immune response to Ixodes ricinus tick bites in human skin.

    Science.gov (United States)

    Glatz, Martin; Means, Terry; Haas, Josef; Steere, Allen C; Müllegger, Robert R

    2017-03-01

    Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick-host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick-bite skin lesions (skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Early developmental responses to seedling environment modulate later plasticity to light spectral quality.

    Directory of Open Access Journals (Sweden)

    Eric J B von Wettberg

    Full Text Available Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation and simulated foliage shade (which affects phytochrome-mediated shade avoidance. Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red:far red (R:FR. Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments.

  5. Response of Soybean to Early-Season Planting Dates along the Upper Texas Gulf Coast

    Directory of Open Access Journals (Sweden)

    W. James Grichar

    2014-01-01

    Full Text Available Soybeans (Glycine max L. can be planted along the upper Texas Gulf Coast from mid-March through May to take advantage of early season rains and to complete harvest before hurricane season and fall rains become a problem. However, in the Calhoun County area (28.5° north latitude, these planting dates have resulted in below average yields and reasons for these yield reductions are not clear. To determine if earlier planting dates could be an option to eliminate the low yields, field studies were conducted from 2005 through 2010 in Calhoun County, Texas, to determine soybean cultivar response to planting dates which ranged from mid-February through the last of April. Typically, soil temperatures in this area are above 18°C in mid-February and depending on weather patterns may not fall much lower during any time in the early portion of the growing season. The greatest yield was obtained with the mid-February and mid-March planting dates compared with early- or late-April planting dates. Typically, as planting date was delayed, the interval between planting and harvest decreased.

  6. Biophysical response of living cells to boron nitride nanoparticles: uptake mechanism and bio-mechanical characterization

    Energy Technology Data Exchange (ETDEWEB)

    Rasel, Md. Alim Iftekhar; Li, Tong; Nguyen, Trung Dung; Singh, Sanjleena [Queensland University of Technology (QUT), School of Chemistry, Physics and Mechanical Engineering (Australia); Zhou, Yinghong; Xiao, Yin [Queensland University of Technology (QUT), Institute of Health and Biomedical Innovation (Australia); Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [Queensland University of Technology (QUT), School of Chemistry, Physics and Mechanical Engineering (Australia)

    2015-11-15

    Boron nitride nanomaterials have attracted significant interest due to their superior chemical and physical properties. Despite these novel properties, investigation on the interaction between boron nitride nanoparticle (BN NP) and living systems has been limited. In this study, BN NP (100–250 nm) is assessed as a promising biomaterial for medical applications. The toxicity of BN NP is evaluated by assessing the cells behaviours both biologically (MTT assay, ROS detection etc.) and physically (atomic force microscopy). The uptake mechanism of BN NP is studied by analysing the alternations in cellular morphology based on cell imaging techniques. The results demonstrate in vitro cytocompatibility of BN NP with immense potential for use as an effective nanoparticle for various bio-medical applications.

  7. A quantum-mechanical perspective on linear response theory within polarizable embedding

    DEFF Research Database (Denmark)

    List, Nanna Holmgaard; Norman, Patrick; Kongsted, Jacob

    2017-01-01

    We present a derivation of linear response theory within polarizable embedding starting from a rigorous quantum-mechanical treatment of a composite system. To this aim, two different subsystem decompositions (symmetric and nonsymmetric) of the linear response function are introduced and the pole...

  8. Genetics of mechanisms controlling responses to two major pathogens in broiler and layer chickens

    DEFF Research Database (Denmark)

    Hamzic, Edin

    The objective of this thesis was to improve the understanding of molecular mechanisms controlling the response to two major pathogens, Eimeria maxima (coccidiosis) and infectious bronchitis virus (IBV), in broiler and layer chickens, respectively. Breeding for the improved response to the two...

  9. Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice

    NARCIS (Netherlands)

    Callewaert, F.; Bakker, A.; Schrooten, J.; Van Meerbeek, B.; Verhoeven, G.; Boonen, S.; Vanderschueren, D.

    2010-01-01

    In female mice, estrogen receptor-alpha (ERα) mediates the anabolic response of bone to mechanical loading. Whether ERα plays a similar role in the male skeleton and to what extent androgens and androgen receptor (AR) affect this response in males remain unaddressed. Therefore, we studied the

  10. Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

    International Nuclear Information System (INIS)

    Ahmed, M.

    2003-01-01

    Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

  11. Distribution of Endogenous NO Regulates Early Gravitropic Response and PIN2 Localization in Arabidopsis Roots

    Directory of Open Access Journals (Sweden)

    Ramiro París

    2018-04-01

    Full Text Available High-resolution and automated image analysis of individual roots demonstrated that endogenous nitric oxide (NO contribute significantly to gravitropism of Arabidopsis roots. Lowering of endogenous NO concentrations strongly reduced and even reversed gravitropism, resulting in upward bending, without affecting root growth rate. Notably, the asymmetric accumulation of NO along the upper and lower sides of roots correlated with a positive gravitropic response. Detection of NO by the specific DAF-FM DA fluorescent probe revealed that NO was higher at the lower side of horizontally-oriented roots returning to initial values 2 h after the onset of gravistimulation. We demonstrate that NO promotes plasma membrane re-localization of PIN2 in epidermal cells, which is required during the early root gravitropic response. The dynamic and asymmetric localization of both auxin and NO is critical to regulate auxin polar transport during gravitropism. Our results collectively suggest that, although auxin and NO crosstalk occurs at different levels of regulation, they converge in the regulation of PIN2 membrane trafficking in gravistimulated roots, supporting the notion that a temporally and spatially coordinated network of signal molecules could participate in the early phases of auxin polar transport during gravitropism.

  12. Ultrasonic RF time series for early assessment of the tumor response to chemotherapy.

    Science.gov (United States)

    Lin, Qingguang; Wang, Jianwei; Li, Qing; Lin, Chunyi; Guo, Zhixing; Zheng, Wei; Yan, Cuiju; Li, Anhua; Zhou, Jianhua

    2018-01-05

    Ultrasound radio-frequency (RF) time series have been shown to carry tissue typing information. To evaluate the potential of RF time series for early prediction of tumor response to chemotherapy, 50MCF-7 breast cancer-bearing nude mice were randomized to receive cisplatin and paclitaxel (treatment group; n = 26) or sterile saline (control group; n = 24). Sequential ultrasound imaging was performed on days 0, 3, 6, and 8 of treatment to simultaneously collect B-mode images and RF data. Six RF time series features, slope, intercept, S1, S2, S3 , and S4 , were extracted during RF data analysis and contrasted with microstructural tumor changes on histopathology. Chemotherapy administration reduced tumor growth relative to control on days 6 and 8. Compared with day 0, intercept, S1 , and S2 were increased while slope was decreased on days 3, 6, and 8 in the treatment group. Compared with the control group, intercept, S1, S2, S3 , and S4 were increased, and slope was decreased, on days 3, 6, and 8 in the treatment group. Tumor cell density decreased significantly in the latter on day 3. We conclude that ultrasonic RF time series analysis provides a simple way to noninvasively assess the early tumor response to chemotherapy.

  13. Abnormal early gamma responses to emotional faces differentiate unipolar from bipolar disorder patients.

    Science.gov (United States)

    Liu, T Y; Chen, Y S; Su, T P; Hsieh, J C; Chen, L F

    2014-01-01

    This study investigates the cortical abnormalities of early emotion perception in patients with major depressive disorder (MDD) and bipolar disorder (BD) using gamma oscillations. Twenty-three MDD patients, twenty-five BD patients, and twenty-four normal controls were enrolled and their event-related magnetoencephalographic responses were recorded during implicit emotional tasks. Our results demonstrated abnormal gamma activity within 100 ms in the emotion-related regions (amygdala, orbitofrontal (OFC) cortex, anterior insula (AI), and superior temporal pole) in the MDD patients, suggesting that these patients may have dysfunctions or negativity biases in perceptual binding of emotional features at very early stage. Decreased left superior medial frontal cortex (smFC) responses to happy faces in the MDD patients were correlated with their serious level of depression symptoms, indicating that decreased smFC activity perhaps underlies irregular positive emotion processing in depressed patients. In the BD patients, we showed abnormal activation in visual regions (inferior/middle occipital and middle temporal cortices) which responded to emotional faces within 100 ms, supporting that the BD patients may hyperactively respond to emotional features in perceptual binding. The discriminant function of gamma activation in the left smFC, right medial OFC, right AI/inferior OFC, and the right precentral cortex accurately classified 89.6% of patients as unipolar/bipolar disorders.

  14. Radiofrequency ablation of liver cancer: early evaluation of therapeutic response with contrast-enhanced ultrasonography

    International Nuclear Information System (INIS)

    Choi, Dong Gil; Lim, Hyo K.; Lee, Won Jae; Kim, Seung Hoon; Kim, Min Ju; Kim, Seung Kwon; Jang, Kyung Mi; Lee, Ji Yeon; Lim, Jae Hoon

    2004-01-01

    The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation

  15. The Long-term Impact of Early Life Pain On Adult Responses to Anxiety and Stress: Historical Perspectives and Empirical Evidence

    Science.gov (United States)

    Victoria, Nicole C.; Murphy, Anne Z.

    2016-01-01

    Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10–18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. PMID:26210872

  16. The impact of early repeated pain experiences on stress responsiveness and emotionality at maturity in rats.

    Science.gov (United States)

    Page, Gayle G; Blakely, Wendy P; Kim, Miyong

    2005-01-01

    The intensive care necessary for premature newborns is characterized by multiple procedures, many of which are painful. Given emerging evidence that such early pain during this time of high brain plasticity may affect long-term neurodevelopmental and social-emotional functioning, this study explored the impact of early repeated pain on emotionality and stress responsivity at maturity. From birth through postnatal day 7, Fischer 344 pups underwent either paw needle prick every day versus every other day or daily paw touch, or were left unperturbed. Each paw received the designated perturbation once per day. At maturity, some animals underwent emotionality testing: either a 4-day series of open field exposures or a single elevated plus-maze (EPM) exposure. The paw prick groups exhibited less open field habituation and occupied the EPM open arms more. Two weeks later, all animals were either subjected to forced swim or not. At 1h post-swim, animals underwent either blood withdrawal for plasma corticosterone (CS) levels and ex vivo natural killer cell activity (NKCA) or were injected intravenously with radiolabeled NK-sensitive syngeneic MADB106 tumor cells and assessed for lung tumor retention. Sex was a major factor in the manifestation of perturbation-related differences in the biologic outcomes. Whereas postnatal pain differentially affected baseline tumor retention between males and females, only males exhibited perturbation-related differences in swim stress-induced increases in tumor retention and CS. Finally, male-female differences were evident in CS, NKCA, and tumor responses to swim stress. These findings suggest that early pain affects neurodevelopmental function in the mature organism; however, these relationships are complicated by sex differences, the postnatal pain schedule, and the outcome measured.

  17. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    Science.gov (United States)

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Mechanical and thermo-mechanical response of a lead-core bearing device subjected to different loading conditions

    Directory of Open Access Journals (Sweden)

    Zhelyazov Todor

    2018-01-01

    Full Text Available The contribution is focused on the numerical modelling, simulation and analysis of a lead-core bearing device for passive seismic isolation. An accurate finite element model of a lead-core bearing device is presented. The model is designed to analyse both mechanical and thermo-mechanical responses of the seismic isolator to different loading conditions. Specifically, the mechanical behaviour in a typical identification test is simulated. The response of the lead-core bearing device to circular sinusoidal paths is analysed. The obtained shear displacement – shear force relationship is compared to experimental data found in literature sources. The hypothesis that heating of the lead-core during cyclic loading affects the degrading phenomena in the bearing device is taken into account. Constitutive laws are defined for each material: lead, rubber and steel. Both predefined constitutive laws (in the used general–purpose finite element code and semi-analytical procedures aimed at a more accurate modelling of the constitutive relations are tested. The results obtained by finite element analysis are to be further used to calibrate a macroscopic model of the lead-core bearing device seen as a single-degree-of-freedom mechanical system.

  19. Fish oil supplementation in early infancy modulates developing infant immune responses.

    Science.gov (United States)

    D'Vaz, N; Meldrum, S J; Dunstan, J A; Lee-Pullen, T F; Metcalfe, J; Holt, B J; Serralha, M; Tulic, M K; Mori, T A; Prescott, S L

    2012-08-01

    Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema. To examine the effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease. In a double-blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil [containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA-DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age. DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P acid (PUFA) levels and associated with lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n-3 PUFA having immunomodulatory properties that are potentially allergy-protective. © 2012 Blackwell Publishing Ltd.

  20. Predictive value of early viriological response for sustained viriological response in chronic hepatitis c with conventional interferon therapy

    International Nuclear Information System (INIS)

    Awan, A.; Umar, M.; Khaar, H.T.B.; Kulsoom, A.; Minhas, Z.; Ambreen, S.; Habib, N.; Mumtaz, W.; Habib, F.

    2016-01-01

    Background: Hepatitis is a major public health problem in Pakistan due to its strong association with liver failure and hepatocellular carcinoma. In Pakistan, conventional interferon therapy along with Ribavirin is favoured especially in Government funded programs for treatment of Hepatitis C, over the more expensive Pegylated Interferon and Ribavirin combination therapy as recommended by Pakistan society of Gastroenterology and GI endoscopy due to its favourable results observed in genotype 3 which is the dominant genotype of this region. Objective of our study was to assess the viriological responses with standard interferon therapy and to determine the predictive values of early viriological response (EVR) for Sustained Viriological Response (SVR) in chronic hepatitis C patients treated with standard interferon therapy. Methods: A cross sectional study was conducted on patients with chronic hepatitis C having received standard interferon and ribavirin therapy for six months. EVR and SVR were noted for analysis. Positive and negative predictive values of EVR on SVR were calculated. Results: Out of the total sample (N=3075), 1946 (63.3 percentage) patients were tested for EVR. 1386 (71.2 percentage) were positive while 560 (28.8 percentage) were negative while 516 (16.8 percentage) were tested for SVR. Two hundred and eighty-five (55.2 percentage) were positive while 231 (44.8 percentage) were negative. EVR and SVR tested were N=117. Positive predictive value of EVR on SVR was 67.1 percentage and negative predictive value was 65.8 percentage. Statistically significant association between EVR and SVR was determined with Chi square statistic of 11.8 (p-value <0.0001). Conclusion: EVR is a good predictor of response of patients to standard interferon and ribavirin therapy. In the absence of an EVR, it seems imperative to stop further treatment. Virilogical responses with conventional interferon therapy are comparable to those of pegylated interferon therapy so

  1. Early Head Start and African American Families: Impacts and Mechanisms of Child Outcomes

    Science.gov (United States)

    Harden, Brenda Jones; Sandstrom, Heather; Chazan-Cohen, Rachel

    2012-01-01

    Persistent disparities exist between African American children and their European American counterparts across developmental domains. Early childhood intervention may serve to promote more positive outcomes among African American children. The current study examined whether and how the Early Head Start (EHS) program benefited African American…

  2. Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Ye W

    2014-05-01

    Full Text Available Wenyu Ye,1 William Montgomery,2 Zbigniew Kadziola,3 Li Liu,4 Haibo Xue,4 Michael D Stensland,5 Tamas Treuer61Real World Analytics, Eli Lilly and Company, Indianapolis, IN, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Real World Analytics Capabilities, Eli Lilly GmbH, Vienna, Austria; 4Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, People’s Republic of China; 5Agile Outcomes Research, Inc., Rochester, MN, USA; 6Neuroscience Research, Eli Lilly and Company, Budapest, HungaryBackground: The aims of this analysis were to identify factors associated with early response (at 4 weeks to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People’s Republic of China.Methods: A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330. Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine.Results: One hundred and thirty patients (40% achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15–1.97, fewer years since first diagnosis (OR 0.94, CI 0.90–0.98, a greater number of social activities (OR 1.22, CI 1.05–1.40, participation in a weight control program (OR 1.81, CI 1.04–3.15, and high adherence

  3. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

    Science.gov (United States)

    Duffy, T A; Iwanowicz, L R; McCormick, S D

    2014-07-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

  4. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

    Science.gov (United States)

    Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

    2018-03-15

    Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

  5. Ethanol, saccharin, and quinine: early ontogeny of taste responsiveness and intake.

    Science.gov (United States)

    Kozlov, Andrey P; Varlinskaya, Elena I; Spear, Norman E

    2008-02-01

    Rat pups demonstrate high levels of immediate acceptance of ethanol during the first 2 weeks of postnatal life. Given that the taste of ethanol is most likely perceived by infant rats as a combination of sweet and bitter, high intake of ethanol early in ontogeny may be associated with age-related enhanced responsiveness to the sweet component of ethanol taste, as well as with ontogenetic decreases in sensitivity to its bitter component. Therefore, the present study compared responsiveness to ethanol and solutions with bitter (quinine) and sweet (saccharin) taste in terms of intake and palatability across the first 2 weeks of postnatal life. Characteristic patterns of responsiveness to 10% (v/v) ethanol, 0.1% saccharin, 0.2% quinine, and water in terms of taste reactivity and fluid intake were assessed in rat pups tested on postnatal day (P) 4, 9, or 12 using a new technique of on-line monitoring of fluid flow through a two-channel intraoral cannula. Taste reactivity included analysis of ingestive and aversive responses following six intraoral infusions of the test fluids. This taste reactivity probe was followed by the intake test, in which animals were allowed to voluntarily ingest fluids from an intraoral cannula. Pups of all ages showed more appetitive responses to saccharin and ethanol than to water or quinine. No age-related differences were apparent in taste responsiveness to saccharin and ethanol. However, the age-related pattern of ethanol intake drastically differed from that of saccharin. Intake of saccharin increased from P4 to P9 and decreased substantially by P12, whereas intake of ethanol gradually increased from P4 to P12. Intake of ethanol was significantly lower than intake of saccharin on P9, whereas P12 pups took in more ethanol than saccharin. The findings of the present study indicate ontogenetic dissociations between taste reactivity to ethanol and saccharin and intake of these solutions, and suggest that high acceptance of ethanol early in

  6. Comparison of the Mechanical Properties of Early Leukocyte- and Platelet-Rich Fibrin versus PRGF/Endoret Membranes

    Directory of Open Access Journals (Sweden)

    Hooman Khorshidi

    2016-01-01

    Full Text Available Objectives. The mechanical properties of membranes are important factors in the success of treatment and clinical handling. The goal of this study was to compare the mechanical properties of early leukocyte- and platelet-rich fibrin (L-PRF versus PRGF/Endoret membrane. Materials and Methods. In this experimental study, membranes were obtained from 10 healthy male volunteers. After obtaining 20 cc venous blood from each volunteer, 10 cc was used to prepare early L-PRF (group 1 and the rest was used to get a membrane by PRGF-Endoret system (group 2. Tensile loads were applied to specimens using universal testing machine. Tensile strength, stiffness, and toughness of the two groups of membranes were calculated and compared by paired t-test. Results. The mean tensile strength and toughness were higher in group 1 with a significant difference (P0.05. Conclusions. The results showed that early L-PRF membranes had stronger mechanical properties than membranes produced by PRGF-Endoret system. Early L-PRF membranes might have easier clinical handling and could be a more proper scaffold in periodontal regenerative procedures. The real results of the current L-PRF should be in fact much higher than what is reported here.

  7. Comparison of the Mechanical Properties of Early Leukocyte- and Platelet-Rich Fibrin versus PRGF/Endoret Membranes.

    Science.gov (United States)

    Khorshidi, Hooman; Raoofi, Saeed; Bagheri, Rafat; Banihashemi, Hodasadat

    2016-01-01

    Objectives. The mechanical properties of membranes are important factors in the success of treatment and clinical handling. The goal of this study was to compare the mechanical properties of early leukocyte- and platelet-rich fibrin (L-PRF) versus PRGF/Endoret membrane. Materials and Methods. In this experimental study, membranes were obtained from 10 healthy male volunteers. After obtaining 20 cc venous blood from each volunteer, 10 cc was used to prepare early L-PRF (group 1) and the rest was used to get a membrane by PRGF-Endoret system (group 2). Tensile loads were applied to specimens using universal testing machine. Tensile strength, stiffness, and toughness of the two groups of membranes were calculated and compared by paired t-test. Results. The mean tensile strength and toughness were higher in group 1 with a significant difference (P 0.05). Conclusions. The results showed that early L-PRF membranes had stronger mechanical properties than membranes produced by PRGF-Endoret system. Early L-PRF membranes might have easier clinical handling and could be a more proper scaffold in periodontal regenerative procedures. The real results of the current L-PRF should be in fact much higher than what is reported here.

  8. Metabolic profiles of flooding-tolerant mechanism in early-stage soybean responding to initial stress.

    Science.gov (United States)

    Wang, Xin; Zhu, Wei; Hashiguchi, Akiko; Nishimura, Minoru; Tian, Jingkui; Komatsu, Setsuko

    2017-08-01

    Metabolomic analysis of flooding-tolerant mutant and abscisic acid-treated soybeans suggests that accumulated fructose might play a role in initial flooding tolerance through regulation of hexokinase and phosphofructokinase. Soybean is sensitive to flooding stress, which markedly reduces plant growth. To explore the mechanism underlying initial-flooding tolerance in soybean, mass spectrometry-based metabolomic analysis was performed using flooding-tolerant mutant and abscisic-acid treated soybeans. Among the commonly-identified metabolites in both flooding-tolerant materials, metabolites involved in carbohydrate and organic acid displayed same profile at initial-flooding stress. Sugar metabolism was highlighted in both flooding-tolerant materials with the decreased and increased accumulation of sucrose and fructose, respectively, compared to flooded soybeans. Gene expression of hexokinase 1 was upregulated in flooded soybean; however, it was downregulated in both flooding-tolerant materials. Metabolites involved in carbohydrate/organic acid and proteins related to glycolysis/tricarboxylic acid cycle were integrated. Increased protein abundance of phosphofructokinase was identified in both flooding-tolerant materials, which was in agreement with its enzyme activity. Furthermore, sugar metabolism was pointed out as the tolerant-responsive process at initial-flooding stress with the integration of metabolomics, proteomics, and transcriptomics. Moreover, application of fructose declined the increased fresh weight of plant induced by flooding stress. These results suggest that fructose might be the critical metabolite through regulation of hexokinase and phosphofructokinase to confer initial-flooding stress in soybean.

  9. Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

    Science.gov (United States)

    Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

    2015-01-01

    A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

  10. Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.

    Science.gov (United States)

    Suchorska, Wiktoria Maria; Augustyniak, Ewelina; Łukjanow, Magdalena

    2017-04-01

    Despite the well-demonstrated efficacy of stem cell (SC) therapy, this approach has a number of key drawbacks. One important concern is the response of pluripotent SCs to treatment with ionizing radiation (IR), given that SCs used in regenerative medicine will eventually be exposed to IR for diagnostic or treatment‑associated purposes. Therefore, the aim of the present study was to examine and compare early IR‑induced responses of pluripotent SCs to assess their radioresistance and radiosensitivity. In the present study, 3 cell lines; human embryonic SCs (hESCs), human induced pluripotent SCs (hiPSCs) and primary human dermal fibroblasts (PHDFs); were exposed to IR at doses ranging from 0 to 15 gray (Gy). Double strand breaks (DSBs), and the gene expression of the following DNA repair genes were analyzed: P53; RAD51; BRCA2; PRKDC; and XRCC4. hiPSCs demonstrated greater radioresistance, as fewer DSBs were identified, compared with hESCs. Both pluripotent SC lines exhibited distinct gene expression profiles in the most common DNA repair genes that are involved in homologous recombination, non‑homologous end‑joining and enhanced DNA damage response following IR exposure. Although hESCs and hiPSCs are equivalent in terms of capacity for pluripotency and differentiation into 3 germ layers, the results of the present study indicate that these 2 types of SCs differ in gene expression following exposure to IR. Consequently, further research is required to determine whether hiPSCs and hESCs are equally safe for application in clinical practice. The present study contributes to a greater understanding of DNA damage response (DDR) mechanisms activated in pluripotent SCs and may aid in the future development of safe SC‑based clinical protocols.

  11. Invasive species information networks: Collaboration at multiple scales for prevention, early detection, and rapid response to invasive alien species

    Science.gov (United States)

    Simpson, Annie; Jarnevich, Catherine S.; Madsen, John; Westbrooks, Randy G.; Fournier, Christine; Mehrhoff, Les; Browne, Michael; Graham, Jim; Sellers, Elizabeth A.

    2009-01-01

    Accurate analysis of present distributions and effective modeling of future distributions of invasive alien species (IAS) are both highly dependent on the availability and accessibility of occurrence data and natural history information about the species. Invasive alien species monitoring and detection networks (such as the Invasive Plant Atlas of New England and the Invasive Plant Atlas of the MidSouth) generate occurrence data at local and regional levels within the United States, which are shared through the US National Institute of Invasive Species Science. The Inter-American Biodiversity Information Network's Invasives Information Network (I3N), facilitates cooperation on sharing invasive species occurrence data throughout the Western Hemisphere. The I3N and other national and regional networks expose their data globally via the Global Invasive Species Information Network (GISIN). International and interdisciplinary cooperation on data sharing strengthens cooperation on strategies and responses to invasions. However, limitations to effective collaboration among invasive species networks leading to successful early detection and rapid response to invasive species include: lack of interoperability; data accessibility; funding; and technical expertise. This paper proposes various solutions to these obstacles at different geographic levels and briefly describes success stories from the invasive species information networks mentioned above. Using biological informatics to facilitate global information sharing is especially critical in invasive species science, as research has shown that one of the best indicators of the invasiveness of a species is whether it has been invasive elsewhere. Data must also be shared across disciplines because natural history information (e.g. diet, predators, habitat requirements, etc.) about a species in its native range is vital for effective prevention, detection, and rapid response to an invasion. Finally, it has been our

  12. The relationship between early ego strength and adolescent responses to the threat of nuclear war

    International Nuclear Information System (INIS)

    Andrekus, N.J.

    1989-01-01

    Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war, how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development

  13. Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy.

    Science.gov (United States)

    Sabir, Adeel; Schor-Bardach, Rachel; Wilcox, Carol J; Rahmanuddin, Syed; Atkins, Michael B; Kruskal, Jonathan B; Signoretti, Sabina; Raptopoulos, Vassilios D; Goldberg, S Nahum

    2008-07-01

    The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

  14. The relationship between early ego strength and adolescent responses to the threat of nuclear war

    Energy Technology Data Exchange (ETDEWEB)

    Andrekus, N.J.

    1989-01-01

    Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war, how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development.

  15. Phenological behaviour of early spring flowering trees in Spain in response to recent climate changes

    Science.gov (United States)

    Hidalgo-Galvez, M. D.; García-Mozo, H.; Oteros, J.; Mestre, A.; Botey, R.; Galán, C.

    2018-04-01

    This research reports the phenological trends of four early spring and late winter flowering trees in Spain (south Europe) from a recent period (1986-2012). The studied species were deciduous trees growing in different climatic areas: hazel ( Corylus avellana L.), willow ( Salix alba L.), ash ( Fraxinus angustifolia Vahl.) and white mulberry ( Morus alba L.). We analysed the response to climate and the trends of the following phenophases observed at the field: budburst, leaf unfolding, flowering, fruit ripening, fruit harvesting, leaf colour change and leaf-fall. The study was carried out in 17 sampling sites in the country with the aim of detecting the recent phenological response to the climate of these species, and the possible effect of climate change. We have observed differences in the phenological response to climate depending on each species. Sixty-one percent of studied sites suffered an advance of early spring phenophases, especially budburst on average by -0.67 days and flowering on average by -0.15 days during the studied period, and also in the subsequent fruit ripening and harvesting phases on average by -1.06 days. By contrast, it has been detected that 63% of sampling sites showed a delay in autumn vegetative phases, especially leaf-fall events on average by +1.15 days. The statistic correlation analysis shows in the 55% of the studied localities that phenological advances are the consequence of the increasing trend detected for temperature—being minimum temperature the most influential factor—and in the 52% of them, phenological advances occurred by rainfall variations. In general, leaf unfolding and flowering from these species showed negative correlations in relation to temperature and rainfall, whereas that leaf colour change and leaf-fall presented positive correlations. The results obtained have a great relevance due to the fact that they can be considered as reliable bio-indicators of the impact of the recent climate changes in southern

  16. Characterization of mechanical behavior of an epithelial monolayer in response to epidermal growth factor stimulation

    International Nuclear Information System (INIS)

    Yang, Ruiguo; Chen, Jennifer Y.; Xi, Ning; Lai, King Wai Chiu; Qu, Chengeng; Fung, Carmen Kar Man; Penn, Lynn S.; Xi, Jun

    2012-01-01

    Cell signaling often causes changes in cellular mechanical properties. Knowledge of such changes can ultimately lead to insight into the complex network of cell signaling. In the current study, we employed a combination of atomic force microscopy (AFM) and quartz crystal microbalance with dissipation monitoring (QCM-D) to characterize the mechanical behavior of A431 cells in response to epidermal growth factor receptor (EGFR) signaling. From AFM, which probes the upper portion of an individual cell in a monolayer of cells, we observed increases in energy dissipation, Young's modulus, and hysteresivity. Increases in hysteresivity imply a shift toward a more fluid-like mechanical ordering state in the bodies of the cells. From QCM-D, which probes the basal area of the monolayer of cells collectively, we observed decreases in energy dissipation factor. This result suggests a shift toward a more solid-like state in the basal areas of the cells. The comparative analysis of these results indicates a regionally specific mechanical behavior of the cell in response to EGFR signaling and suggests a correlation between the time-dependent mechanical responses and the dynamic process of EGFR signaling. This study also demonstrates that a combination of AFM and QCM-D is able to provide a more complete and refined mechanical profile of the cells during cell signaling. -- Highlights: ► The EGF-induced cellular mechanical response is regionally specific. ► The EGF-induced cellular mechanical response is time and dose dependent. ► A combination of AFM and QCM-D provides a more complete mechanical profile of cells.

  17. Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

    Science.gov (United States)

    Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

    2009-01-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8+ T cell recognition, and demonstrate that the Early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-α– dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection. PMID:19786304

  18. Role of alveolar epithelial early growth response-1 (Egr-1) in CD8+ T cell-mediated lung injury.

    Science.gov (United States)

    Ramana, Chilakamarti V; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung-Joo; Enelow, Richard I

    2009-12-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8(+) T cells in this injury, and have found that the critical effector molecule is TNF-alpha expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8(+) T cell recognition, and demonstrate that the early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-alpha-dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection.

  19. Early activation of natural killer and B cells in response to primary dengue virus infection in A/J mice

    International Nuclear Information System (INIS)

    Shresta, Sujan; Kyle, Jennifer L.; Robert Beatty, P.; Harris, Eva

    2004-01-01

    Dengue virus (DEN) causes the most prevalent arthropod-borne viral illness in humans worldwide. Immune mechanisms that are involved in protection and pathogenesis of DEN infection have not been fully elucidated due largely to the lack of an adequate animal model. Therefore, as a first step, we characterized the primary immune response in immunocompetent inbred A/J mice that were infected intravenously with a non-mouse-adapted DEN type 2 (DEN2) strain. A subset (55%) of infected mice developed paralysis by 14 days post-infection (p.i.), harbored infectious DEN in the central nervous system (CNS), and had an elevated hematocrit and a decreased white blood cell (WBC) count. Immunologic studies detected (i) increased numbers of CD69 + splenic natural killer (NK) and B cells at day 3 p.i., (ii) DEN-specific IgM and IgG responses by days 3 and 7 p.i., respectively, and (iii) splenocyte production of IFNγ at day 14 p.i. We conclude that the early activities of NK cells, B cells and IgM, and later actions of IFNγ and IgG likely play a role in the defense against DEN infection

  20. Importance of Bacterial Replication and Alveolar Macrophage-Independent Clearance Mechanisms during Early Lung Infection with Streptococcus pneumoniae

    Science.gov (United States)

    Camberlein, Emilie; Cohen, Jonathan M.; José, Ricardo; Hyams, Catherine J.; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A.; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad

    2015-01-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae. PMID:25583525

  1. Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Laura A E Hughes

    Full Text Available BACKGROUND: Exposure to energy restriction during childhood and adolescence is associated with a lower risk of developing colorectal cancer (CRC. Epigenetic dysregulation during this critical period of growth and development may be a mechanism to explain such observations. Within the Netherlands Cohort Study on diet and cancer, we investigated the association between early life energy restriction and risk of subsequent CRC characterized by the (promoter CpG island methylation phenotype (CIMP. METHODOLOGY/PRINCIPAL FINDINGS: Information on diet and risk factors was collected by baseline questionnaire (n = 120,856. Three indicators of exposure were assessed: place of residence during the Hunger Winter (1944-45 and World War II years (1940-44, and father's employment status during the Economic Depression (1932-40. Methylation specific PCR (MSP on DNA from paraffin embedded tumor tissue was performed to determine CIMP status according to the Weisenberger markers. After 7.3 years of follow-up, 603 cases and 4631 sub-cohort members were available for analysis. Cox regression was used to calculate hazard ratios (HR and 95% confidence intervals for CIMP+ (27.7% and CIMP- (72.3% tumors according to the three time periods of energy restriction, adjusted for age and gender. Individuals exposed to severe famine during the Hunger Winter had a decreased risk of developing a tumor characterized by CIMP compared to those not exposed (HR 0.65, 95%CI: 0.45-0.92. Further categorizing individuals by an index of '0-1' '2-3' or '4-7' genes methylated in the promoter region suggested that exposure to the Hunger Winter was associated with the degree of promoter hypermethylation ('0-1 genes methylated' HR = 1.01, 95%CI:0.74-1.37; '2-3 genes methylated' HR = 0.83, 95% CI:0.61-1.15; '4-7 genes methylated' HR = 0.72, 95% CI:0.49-1.04. No associations were observed with respect to the Economic Depression and WWII years. CONCLUSIONS: This is the first study indicating that

  2. Experimental studies of the dynamic mechanical response of a single polymer chain

    DEFF Research Database (Denmark)

    Thormann, Esben; Evans, Drew R.; Craig, Vincent S. J.

    2006-01-01

    The high-frequency and low-amplitude dynamic mechanical response from a single poly(vinyl alcohol) chain was investigated. Modification of a commercial atomic force microscope enabled high-frequency and low-amplitude periodic deformations of polymer chains during extension to be performed...... mechanical response from poly(vinyl alcohol) does not differ from its static response. This result is not unexpected as poly(vinyl alcohol) is a highly flexible polymer with intramolecular relaxation processes taking place on a short time scale. The choice of a polymer with a fast relaxation allows its...... static properties to be recovered from the dynamic measurements and enables the method suggested in this paper for decoupling the polymer response from the hydrodynamic response to be validated....

  3. CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.

    Science.gov (United States)

    Nabbout, Rima; Depienne, Christel; Chipaux, Mathilde; Girard, Benoit; Souville, Isabelle; Trouillard, Oriane; Dulac, Olivier; Chelly, Jamel; Afenjar, Alexandra; Héron, Delphine; Leguern, Eric; Beldjord, Cherif; Bienvenu, Thierry; Bahi-Buisson, Nadia

    2009-11-01

    Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS) is a distinctive epilepsy syndrome often associated with de novo mutations in the SCN1A gene. However, 25-30% patients with SMEI/DS are negative for SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Given the overlapping and heterogeneous clinical features of CDKL5- and ARX-related epilepsies and SMEI/DS, we postulated that CDKL5 mutations in females and ARX mutations gene in males may be associated with early onset seizures forms of SMEI/DS. Twenty-eight patients with early onset SMEI/DS before 6 months negative for SCN1A mutational screening were selected and screened for mutations in the ARX gene in males (n=14) or the CDKL5 gene in females (n=14). No mutations in either gene were found except one intronic variation of uncertain pathogenicity in the CDKL5 gene. All patients started seizures at mean age of 3.48 months. Thirteen patients had familial history of epilepsy or febrile seizures. Patients evolved toward refractory epilepsy with generalized tonic clonic seizures (18/28) and myoclonia (23/28) and severe neurological impairment with autistic features (13/28), ataxia (14/28) and spasticity (5/28). No patient ever exhibited infantile spasms, dystonia, or Rett-like features. Our results illustrate that mutation screening of ARX and CDKL5 is not effective in patients selected on the basis of clinical signs associated to early onset SMEI/DS. In addition, they might reflect that other phenotypic features associated with CDKL5 mutations (Rett-like features, infantile spasm) or ARX mutations (dystonia, spasticity) are more distinctive. 2009 Elsevier B.V. All rights reserved.

  4. Impaired Early-Response Inhibition in Overweight Females with and without Binge Eating Disorder.

    Directory of Open Access Journals (Sweden)

    Jennifer Svaldi

    Full Text Available Several studies report increased reward sensitivity towards food in overweight individuals. By contrast, data is inconclusive with respect to response inhibition in overweight individuals without binge eating disorder (BED. Hence, the latter was addressed in the present study in a group of overweight/obese females with and without BED and a normal-weight control group without eating disorders.A group of women with BED (n = 29, a group of overweight women without BED (n = 33 and normal-weight females (n = 30 participated in a pictorial priming paradigm, with food items (relevant primes and office utensils (neutral primes and color blobs (neutral primes as stimuli. Increased response priming effects (i.e. priming with switches between stimulus categories were taken as indicators of deficient behavioral inhibition.Priming effects for neutral primes were moderate and comparable across all groups. However, primes associated with the food task set lead to increased priming effects in both overweight groups. But, effects were comparable for overweight/obese participants with and without BED.Results suggest that early response inhibition in the context of food is impaired in overweight individuals compared to normal-weight individuals.

  5. Characterization of early cortical population response to thalamocortical input in vitro

    Directory of Open Access Journals (Sweden)

    Michael Raymond Heliodor Hill

    2014-01-01

    Full Text Available The in vitro thalamocortical slice preparation of mouse barrel cortex allows for stimulation of the cortex through its natural afferent thalamocortical pathway. This preparation was used here to investigate the first stage of cortical processing in the large postsynaptic dendritic networks as revealed by voltage sensitive dye imaging. We identified the precise location and dimensions of two clearly distinguishable dendritic networks, one in the granular layer IV and one in the infragranular layer V and VI and showed that they have different physiological properties. DiI fluorescent staining further revealed that thalamocortical axons project on to these two networks in the typical barrel like form, not only in the granular but also in the infragranular layer. Finally we investigated the short term dynamics of both the voltage sensitive dye imaging signal and the local field potential in response to a train of eight-pulses at various frequencies in both these layers. We found evidence of differences in the plasticity between the first two response peaks compared to the remaining six peaks as well as differences in short term plasticity between the voltage sensitive dye imaging response and the local field potential. Our findings suggest, that at least early cortical processing takes place in two separate dendritic networks that may stand at the beginning of further parallel computation. The detailed characterization of the parameters of these networks may provide tools for further research into the complex dynamics of large dendritic networks and their role in cortical computation.

  6. Modifications of glucocorticoid receptors mRNA expression in the hypothalamic-pituitary-adrenal axis in response to early-life stress in female Japanese quail.

    Science.gov (United States)

    Zimmer, C; Spencer, K A

    2014-12-01

    Stress exposure during early-life development can programme individual brain and physiology. The hypothalamic-pituitary-adrenal (HPA) axis is one of the primary targets of this programming, which is generally associated with a hyperactive HPA axis, indicative of a reduced negative-feedback. This reduced feedback efficiency usually results from a reduced level of the glucocorticoid receptor (GR) and/or the mineralocorticoid receptor (MR) within the HPA axis. However, a few studies have shown that early-life stress exposure results in an attenuated physiological stress response, suggesting an enhance feedback efficiency. In the present study, we aimed to determine whether early-life stress had long-term consequences on GR and MR levels in quail and whether the effects on the physiological response to acute stress observed in prenatally stressed individuals were underpinned by changes in GR and/or MR levels in one or more HPA axis components. We determined GR and MR mRNA expression in the hippocampus, hypothalamus and pituitary gland in quail exposed to elevated corticosterone during prenatal development, postnatal development, or both, and in control individuals exposed to none of the stressors. We showed that prenatal stress increased the GR:MR ratio in the hippocampus, GR and MR expression in the hypothalamus and GR expression in the pituitary gland. Postnatal stress resulted in a reduced MR expression in the hippocampus. Both early-life treatments permanently affected the expression of both receptor types in HPA axis regions. The effects of prenatal stress are in accordance with a more efficient negative-feedback within the HPA axis and thus can explain the attenuated stress response observed in these birds. Therefore, these changes in receptor density or number as a consequence of early-life stress exposure might be the mechanism that allows an adaptive response to later-life stressful conditions. © 2014 The Authors. Journal of Neuroendocrinology published by

  7. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  8. Analysis of the mechanical response of biomimetic materials with highly oriented microstructures through 3D printing, mechanical testing and modeling.

    Science.gov (United States)

    de Obaldia, Enrique Escobar; Jeong, Chanhue; Grunenfelder, Lessa Kay; Kisailus, David; Zavattieri, Pablo

    2015-08-01

    Many biomineralized organisms have evolved highly oriented nanostructures to perform specific functions. One key example is the abrasion-resistant rod-like microstructure found in the radular teeth of Chitons (Cryptochiton stelleri), a large mollusk. The teeth consist of a soft core and a hard shell that is abrasion resistant under extreme mechanical loads with which they are subjected during the scraping process. Such remarkable mechanical properties are achieved through a hierarchical arrangement of nanostructured magnetite rods surrounded with α-chitin. We present a combined biomimetic approach in which designs were analyzed with additive manufacturing, experiments, analytical and computational models to gain insights into the abrasion resistance and toughness of rod-like microstructures. Staggered configurations of hard hexagonal rods surrounded by thin weak interfacial material were printed, and mechanically characterized with a cube-corner indenter. Experimental results demonstrate a higher contact resistance and stiffness for the staggered alignments compared to randomly distributed fibrous materials. Moreover, we reveal an optimal rod aspect ratio that lead to an increase in the site-specific properties measured by indentation. Anisotropy has a significant effect (up to 50%) on the Young's modulus in directions parallel and perpendicular to the longitudinal axis of the rods, and 30% on hardness and fracture toughness. Optical microscopy suggests that energy is dissipated in the form of median cracks when the load is parallel to the rods and lateral cracks when the load is perpendicular to the rods. Computational models suggest that inelastic deformation of the rods at early stages of indentation can vary the resistance to penetration. As such, we found that the mechanical behavior of the system is influenced by interfacial shear strain which influences the lateral load transfer and therefore the spread of damage. This new methodology can help to elucidate

  9. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome.

    Science.gov (United States)

    Zhou, Yongfang; Jin, Xiaodong; Lv, Yinxia; Wang, Peng; Yang, Yunqing; Liang, Guopeng; Wang, Bo; Kang, Yan

    2017-11-01

    Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV). A total of 138 patients with ARDS who received mechanical ventilation for mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, P plat , respiratory system compliance, and patient outcomes. Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P mechanical ventilation and ICU stay.

  10. Early life history and habitat ecology of estuarine fishes: responses to natural and human induced change

    Directory of Open Access Journals (Sweden)

    Kenneth Able

    2015-12-01

    Full Text Available Our understanding of the early life history of fishes and their habitats has proceeded from basic natural history to ecology, but we often need to return to natural history to address deficiencies in conceptual and quantitative models of ecosystems. This understanding is further limited by the complex life history of fishes and the lack of appreciation of shifting baselines in estuaries. These inadequacies are especially evident when we try to address the effects of human influences, e.g. fishing, urbanization, and climate change. Often our baselines are inadequate or inaccurate. Our work has detected these along the coasts of the U.S. in extensive time series of larval fish ingress into estuaries, studies of the effects of urbanization, and responses to catastrophes such as the BP oil spill. Long-term monitoring, especially, continues to provide critical insights

  11. Early changes in shoot transcriptome of rice in response to Rhodotorula mucilaginosa JGTA-S1

    Directory of Open Access Journals (Sweden)

    Chinmay Saha

    2015-12-01

    Full Text Available Yeasts of Rhodotorula genus have been reported to show endophytic colonization in different plants. Some of the Rhodotorula species are found to exhibit plant growth promoting activities and also have been reported to protect plants against invading pathogens. A yeast strain closely related to Rhodotorula mucilaginosa was isolated from the endosphere of Typha angustifolia collected from a Uranium mine. A microarray analysis was performed to investigate the early changes in rice shoot transcripts in response to this yeast (R. mucilaginosa JGTA-S1. Transcriptional changes were monitored in 6 h and 24 h treated rice plant shoots as compared to 0 h control. The microarray data has been submitted to the NCBI GEO repository under the accession number of GSE64321.

  12. Late Glacial to Early Holocene socio-ecological responses to climatic instability within the Mediterranean basin

    Science.gov (United States)

    Fernández-López de Pablo, Javier; Jones, Samantha E.; Burjachs, Francesc

    2018-03-01

    The period spanning the Late Glacial and the Early Holocene (≈19-8.2 ka) witnessed a dramatic sequence of climate and palaeoenvironmental changes (Rasmussen et al., 2014). Interestingly, some of the most significant transformations ever documented in human Prehistory took place during this period such as the intensification of hunter-gatherer economic systems, the domestication process of wild plants and animals, and the spread of farming across Eurasia. Understanding the role of climate and environmental dynamics on long-term cultural and economic trajectories, as well as specific human responses to episodes of rapid climate change, still remains as one of the main challenges of archaeological research (Kintigh et al., 2014).

  13. A new definition of boundary point between early reflections and late reverberation in room impulse responses.

    Science.gov (United States)

    Hidaka, Takayuki; Yamada, Yoshinari; Nakagawa, Takehiko

    2007-07-01

    The early reflections in the room impulse response are usually defined as those observed within the initial 80 ms after the arrival of the direct sound, after which time the sound field is called reverberant. This number was chosen from measurements of other functions in a limited number of halls. In order to give an objective foundation to this time separation and to establish a physical indicator for it, a new method is proposed that defines a "transition time t(L)," which is the time at which the energy correlation between the direct plus initial sound and the subsequent decaying sound first achieves a specified low value. For various halls this number is shown and its relevance as a new parameter is discussed.

  14. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria

    DEFF Research Database (Denmark)

    Abdulla, S.; Adam, I.; Adjei, G. O.

    2015-01-01

    values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled...... trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting...... early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included...

  15. Early human bone response to laser metal sintering surface topography: a histologic report.

    Science.gov (United States)

    Mangano, Carlo; Piattelli, Adriano; d'Avila, Susana; Iezzi, Giovanna; Mangano, Francesco; Onuma, Tatiana; Shibli, Jamil Awad

    2010-01-01

    This histologic report evaluated the early human bone response to a direct laser metal sintering implant surface retrieved after a short period of healing. A selective laser sintering procedure using a Ti-6Al-4V alloy powder with a particle size of 25-45 microm prepared this surface topography. One experimental microimplant was inserted into the anterior mandible of a patient during conventional implant surgery of the jaw. The microimplant and surrounding tissues were removed after 2 months of unloaded healing and were prepared for histomorphometric analysis. Histologically, the peri-implant bone appeared in close contact with the implant surface, whereas marrow spaces could be detected in other areas along with prominently stained cement lines. The mean of bone-to-implant contact was 69.51%. The results of this histologic report suggest that the laser metal sintering surface could be a promising alternative to conventional implant surface topographies.

  16. Clonidine improves attentional and memory components of delayed response performance in a model of early Parkinsonism.

    Science.gov (United States)

    Schneider, J S; Tinker, J P; Decamp, E

    2010-08-25

    Cognitive deficits, including attention and working memory deficits, are often described in Parkinson's disease (PD) patients even during the early stages of the disease. However, cognitive deficits associated with PD have proven difficult to treat and often do not respond well to the dopaminergic therapies used to treat the motor symptoms of the disease. Chronic administration of low doses of the neurotoxin 1-methy,4-phenyl,1,2,3,6-tetrahydropyridine (MPTP) can induce cognitive dysfunction in non-human primates, including impaired performance on a variable delayed response (VDR) task with attentional and memory components. Since alpha-2 adrenergic receptor agonists have been suggested to improve attention and working memory in a variety of conditions, the present study assessed the extent to which the alpha-2 noradrenergic agonist clonidine might influence VDR performance in early Parkinsonian non-human primates. Clonidine (0.02-0.10 mg/kg) improved performance on both attentional and memory components of the task, performed in a modified Wisconsin General Test Apparatus, in a dose-dependent manner and the cognition enhancing effects of clonidine were blocked by co-administration of the alpha-2 noradrenergic antagonist idazoxan (0.10 mg/kg). These data suggest that clonidine or drugs of this class, perhaps with greater receptor subtype selectivity and low sedation liability, might be effective therapeutics for cognitive dysfunction associated with PD. Copyright 2010 Elsevier B.V. All rights reserved.

  17. Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: a systematic review protocol.

    Science.gov (United States)

    Stephens, Robert J; Dettmer, Matthew R; Roberts, Brian W; Fowler, Susan A; Fuller, Brian M

    2017-06-09

    Mechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world's literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients. Randomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I 2 statistic. The proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients. This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO #CRD42017057264). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Oral treatment with enrofloxacin early in life promotes Th2-mediated immune response in mice.

    Science.gov (United States)

    Strzępa, Anna; Majewska-Szczepanik, Monika; Kowalczyk, Paulina; Woźniak, Dorota; Motyl, Sylwia; Szczepanik, Marian

    2016-02-01

    Th2 lymphocytes play a crucial role in the development of allergy. These pathologies are caused by coordinated production of the cytokines IL-4, IL-5 and IL-13 that regulate the activity of eosinophils, basophils and B cells. According to the 'hygiene hypothesis', the reduced exposure to microorganisms favors allergy occurrence. The advances in medicine in the field of infection therapy promoted an increasing application of antibiotics which, apart from eliminating pathogens, also partially eliminate the microbiota. Epicutaneous (EC) immunization with ovalbumin (OVA) followed by OVA challenge was used to study the influence of partial gut flora depletion by oral treatment with enrofloxacin on type-2 immune response. Current work describes the influence of enrofloxacin application on anti-OVA antibody production and cytokine synthesis in young and adult mice. Immune response in adult mice is less sensitive to modification of natural gut flora. We observed that enrofloxacin treatment of adult mice leads to significant decrease of anti-OVA IgG2a production while synthesis of anti-OVA IgE was not changed. The production of type-1 (IFN-γ), type-2 (IL-4, IL-5, IL-10, IL-13) and Th17-associated (IL-17A) cytokines was inhibited. On the other hand, treatment of young mice with enrofloxacin significantly upregulates the production of anti-OVA IgE and inhibits the secretion of anti-OVA IgG2a antibodies. Additionally, treatment with enrofloxacin early in life prior to OVA immunization results in increased production of type-2 (IL-4, IL-10 and IL-13) cytokines. Our results clearly indicate that the immune system is more vulnerable to decreased bacterial exposure early in life that may promote development of allergy. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Space radiation-induced bystander effect: kinetics of biologic responses, mechanisms, and significance of secondary radiations

    International Nuclear Information System (INIS)

    Gonon, Geraldine

    2011-01-01

    Widespread evidence indicates that exposure of cell cultures to a particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) 151 keV/μm), 600 MeV/u silicon ions (LET 50 keV/μm) or 290 MeV/u carbon ions (LET 13 keV/μm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u a particles (LET 109 keV/μm). Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only 1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in

  20. Experimental investigation on local mechanical response of superelastic NiTi shape memory alloy

    International Nuclear Information System (INIS)

    Xiao, Yao; Zeng, Pan; Lei, Liping

    2016-01-01

    In this paper, primary attention is paid to the local mechanical response of NiTi shape memory alloy (SMA) under uniaxial tension. With the help of in situ digital image correlation, sets of experiments are conducted to measure the local strain field at various thermomechanical conditions. Two types of mechanical responses of NiTi SMA are identified. The residual strain localization phenomena are observed, which can be attributed to the localized phase transformation (PT) and we affirm that most of the irreversibility is accumulated simultaneously during PT. It is found that temperature and PT play important roles in inducing delocalization of the reverse transformation. We conclude that forward transformation has more influence on the transition of mechanical response in NiTi SMA than reverse transformation in terms of the critical transition temperature for inducing delocalized reverse transformation. (technical note)

  1. Care for Child Development: an intervention in support of responsive caregiving and early child development.

    Science.gov (United States)

    Lucas, J E; Richter, L M; Daelmans, B

    2018-01-01

    An estimated 43% of children younger than 5 years of age are at elevated risk of failing to achieve their human potential. In response, the World Health Organization and UNICEF developed Care for Child Development (CCD), based on the science of child development, to improve sensitive and responsive caregiving and promote the psychosocial development of young children. In 2015, the World Health Organization and UNICEF identified sites where CCD has been implemented and sustained. The sites were surveyed, and responses were followed up by phone interviews. Project reports provided information on additional sites, and a review of published studies was undertaken to document the effectiveness of CCD for improving child and family outcomes, as well as its feasibility for implementation in resource-constrained communities. The inventory found that CCD had been integrated into existing services in diverse sectors in 19 countries and 23 sites, including child survival, health, nutrition, infant day care, early education, family and child protection and services for children with disabilities. Published and unpublished evaluations have found that CCD interventions can improve child development, growth and health, as well as responsive caregiving. It has also been reported to reduce maternal depression, a known risk factor for poor pregnancy outcomes and poor child health, growth and development. Although CCD has expanded beyond initial implementation sites, only three countries reported having national policy support for integrating CCD into health or other services. Strong interest exists in many countries to move beyond child survival to protect and support optimal child development. The United Nations Sustainable Development Goals depend on children realizing their potential to build healthy and emotionally, cognitively and socially competent future generations. More studies are needed to guide the integration of the CCD approach under different conditions. Nevertheless

  2. Early Flood Detection for Rapid Humanitarian Response: Harnessing Near Real-Time Satellite and Twitter Signals

    Directory of Open Access Journals (Sweden)

    Brenden Jongman

    2015-10-01

    Full Text Available Humanitarian organizations have a crucial role in response and relief efforts after floods. The effectiveness of disaster response is contingent on accurate and timely information regarding the location, timing and impacts of the event. Here we show how two near-real-time data sources, satellite observations of water coverage and flood-related social media activity from Twitter, can be used to support rapid disaster response, using case-studies in the Philippines and Pakistan. For these countries we analyze information from disaster response organizations, the Global Flood Detection System (GFDS satellite flood signal, and flood-related Twitter activity analysis. The results demonstrate that these sources of near-real-time information can be used to gain a quicker understanding of the location, the timing, as well as the causes and impacts of floods. In terms of location, we produce daily impact maps based on both satellite information and social media, which can dynamically and rapidly outline the affected area during a disaster. In terms of timing, the results show that GFDS and/or Twitter signals flagging ongoing or upcoming flooding are regularly available one to several days before the event was reported to humanitarian organizations. In terms of event understanding, we show that both GFDS and social media can be used to detect and understand unexpected or controversial flood events, for example due to the sudden opening of hydropower dams or the breaching of flood protection. The performance of the GFDS and Twitter data for early detection and location mapping is mixed, depending on specific hydrological circumstances (GFDS and social media penetration (Twitter. Further research is needed to improve the interpretation of the GFDS signal in different situations, and to improve the pre-processing of social media data for operational use.

  3. The neural mechanisms of semantic and response conflicts: an fMRI study of practice-related effects in the Stroop task.

    Science.gov (United States)

    Chen, Zhencai; Lei, Xu; Ding, Cody; Li, Hong; Chen, Antao

    2013-02-01

    Previous studies have demonstrated that there are separate neural mechanisms underlying semantic and response conflicts in the Stroop task. However, the practice effects of these conflicts need to be elucidated and the possible involvements of common neural mechanisms are yet to be established. We employed functional magnetic resonance imaging (fMRI) in a 4-2 mapping practice-related Stroop task to determine the neural substrates under these conflicts. Results showed that different patterns of brain activations are associated with practice in the attentional networks (e.g., dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and posterior parietal cortex (PPC)) for both conflicts, response control regions (e.g., inferior frontal junction (IFJ), inferior frontal gyrus (IFG)/insula, and pre-supplementary motor areas (pre-SMA)) for semantic conflict, and posterior cortex for response conflict. We also found areas of common activation in the left hemisphere within the attentional networks, for the early practice stage in semantic conflict and the late stage in "pure" response conflict using conjunction analysis. The different practice effects indicate that there are distinct mechanisms underlying these two conflict types: semantic conflict practice effects are attributable to the automation of stimulus processing, conflict and response control; response conflict practice effects are attributable to the proportional increase of conflict-related cognitive resources. In addition, the areas of common activation suggest that the semantic conflict effect may contain a partial response conflict effect, particularly at the beginning of the task. These findings indicate that there are two kinds of response conflicts contained in the key-pressing Stroop task: the vocal-level (mainly in the early stage) and key-pressing (mainly in the late stage) response conflicts; thus, the use of the subtraction method for the exploration of semantic and response conflicts

  4. Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

    Science.gov (United States)

    Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

    2015-01-01

    Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

  5. Molecular analysis of Hsp70 mechanisms in plants and their function in response to stress.

    Science.gov (United States)

    Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

    2017-04-01

    Studying the strategies of improving abiotic stress tolerance is quite imperative and research under this field will increase our understanding of response mechanisms to abiotic stress such as heat. The Hsp70 is an essential regulator of protein having the tendency to maintain internal cell stability like proper folding protein and breakdown of unfolded proteins. Hsp70 holds together protein substrates to help in movement, regulation, and prevent aggregation under physical and or chemical pressure. However, this review reports the molecular mechanism of heat shock protein 70 kDa (Hsp70) action and its structural and functional analysis, research progress on the interaction of Hsp70 with other proteins and their interaction mechanisms as well as the involvement of Hsp70 in abiotic stress responses as an adaptive defense mechanism.

  6. ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal stress in early response to DNA damage.

    Science.gov (United States)

    Jin, Ya-Qiong; An, Guo-Shun; Ni, Ju-Hua; Li, Shu-Yan; Jia, Hong-Ti

    2014-01-01

    The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents disrupt nucleolar structure and function, which results in the stabilization/activation of p53, inducing cell cycle arrest or apoptosis. Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage through transcriptional response and protein-protein interaction. Furthermore, E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1 displays in coordinating DNA damage and nucleolar stress is unclear. In this study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a characteristic feature of nucleolar stress in early response to DNA damage. We found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus was an ATM-dependent and a common event in p53-suficient and -deficient cells. Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which repressed E2F1-dependent rRNA transcription initiation, and was coupled with S phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an indicator for nucleolar stress and a component of ATM pathway, which presumably buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response to DNA damage.

  7. Physical Mechanisms Responsible for Electrical Conduction in Pt/GaN Schottky Diodes

    OpenAIRE

    H. MAZARI; K. AMEUR; N. BENSEDDIK; Z. BENAMARA; R. KHELIFI; M. MOSTEFAOUI; N. ZOUGAGH; N. BENYAHYA; R. BECHAREF; G. BASSOU; B. GRUZZA; J. M. BLUET; C. BRU-CHEVALLIER

    2014-01-01

    The current-voltage (I-V) characteristics of Pt/(n.u.d)-GaN and Pt/Si-doped-GaN diodes Schottky are investigated. Based on these measurements, physical mechanisms responsible for electrical conduction have been suggested. The contribution of thermionic-emission current and various other current transport mechanisms were assumed when evaluating the Schottky barrier height. Thus the generation-recombination, tunneling and leakage currents caused by inhomogeneities and defects at metal-semicondu...

  8. Plasticity of the MAPK signaling network in response to mechanical stress.

    Directory of Open Access Journals (Sweden)

    Andrea M Pereira

    Full Text Available Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms facilitate the crosstalk between the components of these cascades. Yet, the combinatorial complexity of potential molecular interactions between these elements have prevented the understanding of their concerted functions. To analyze the plasticity of the MAPK signaling network in response to mechanical stress we performed a non-saturating epistatic screen in resting and stretched conditions employing as readout a JNK responsive dJun-FRET biosensor. By knocking down MAPKs, and JNK pathway regulators, singly or in pairs in Drosophila S2R+ cells, we have uncovered unexpected regulatory links between JNK cascade kinases, Rho GTPases, MAPKs and the JNK phosphatase Puc. These relationships have been integrated in a system network model at equilibrium accounting for all experimentally validated interactions. This model allows predicting the global reaction of the network to its modulation in response to mechanical stress. It also highlights its context-dependent sensitivity.

  9. Difference between electrostriction kinetics, and mechanical response of segmented polyurethane-based EAP

    Science.gov (United States)

    Jomaa, M. H.; Seveyrat, L.; Perrin, V.; Lebrun, L.; Masenelli-Varlot, K.; Diguet, Gildas; Cavaille, J. Y.

    2017-03-01

    Among the key parameters, which must be taken into account for the choice of actuators used as electrical to mechanical energy converters, the response to a step function and/or the frequency dependence of this response is extremely important. For polymeric actuators and more generally for electroactive polymers, three mechanisms can be at the origin of energy losses, namely dielectric relaxations, viscoelastic relaxations and possible electrical conductivity. In a previous paper, we studied the electrical behavior of segmented polyurethanes with different weight fractions of hard (MDI-BDO) and soft (PTMO) segments. They were shown to exhibit three main mechanisms, namely, from the fastest to the slowest, a secondary or β-relaxation, the main or α-relaxation associated with the glass-rubber transition of the soft phase, and finally, their electrical conductivity. In the present work, we present the general viscoelastic response (as measured through mechanical spectrometry) of the same polyurethanes and their respective time dependent electrostriction responses, and compare it with the relaxation characteristic times of electrical and mechanical spectroscopy data.

  10. Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

    Science.gov (United States)

    Liang, Chang-seng; Huckabee, William E.

    1973-01-01

    When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. These results suggest that the cardiac output response to cyanide infusion consists of three components: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors

  11. Evaluating the Mechanism of Oil Price Shocks and Fiscal Policy Responses in the Malaysian Economy

    International Nuclear Information System (INIS)

    Bekhet, Hussain A; Yusoff, Nora Yusma Mohamed

    2013-01-01

    The paper aims to explore the symmetric impact of oil price shock on economy, to understand its mechanism channel and how fiscal policy response towards it. The Generalized Impulse Response Function and Variance Decomposition under the VAR methodology were employed. The empirical findings suggest that symmetric oil price shock has a positive and direct impact on oil revenue and government expenditure. However, the real GDP is vulnerable in a short-term but not in the long term period. These results would confirm that fiscal policy is the main mechanism channel that mitigates the adverse effects oil price shocks to the economy.

  12. Evaluating the Mechanism of Oil Price Shocks and Fiscal Policy Responses in the Malaysian Economy

    Science.gov (United States)

    Bekhet, Hussain A.; Yusoff, Nora Yusma Mohamed

    2013-06-01

    The paper aims to explore the symmetric impact of oil price shock on economy, to understand its mechanism channel and how fiscal policy response towards it. The Generalized Impulse Response Function and Variance Decomposition under the VAR methodology were employed. The empirical findings suggest that symmetric oil price shock has a positive and direct impact on oil revenue and government expenditure. However, the real GDP is vulnerable in a short-term but not in the long term period. These results would confirm that fiscal policy is the main mechanism channel that mitigates the adverse effects oil price shocks to the economy.

  13. A noise level prediction method based on electro-mechanical frequency response function for capacitors.

    Science.gov (United States)

    Zhu, Lingyu; Ji, Shengchang; Shen, Qi; Liu, Yuan; Li, Jinyu; Liu, Hao

    2013-01-01

    The capacitors in high-voltage direct-current (HVDC) converter stations radiate a lot of audible noise which can reach higher than 100 dB. The existing noise level prediction methods are not satisfying enough. In this paper, a new noise level prediction method is proposed based on a frequency response function considering both electrical and mechanical characteristics of capacitors. The electro-mechanical frequency response function (EMFRF) is defined as the frequency domain quotient of the vibration response and the squared capacitor voltage, and it is obtained from impulse current experiment. Under given excitations, the vibration response of the capacitor tank is the product of EMFRF and the square of the given capacitor voltage in frequency domain, and the radiated audible noise is calculated by structure acoustic coupling formulas. The noise level under the same excitations is also measured in laboratory, and the results are compared with the prediction. The comparison proves that the noise prediction method is effective.

  14. Integrin αv in the mechanical response of osteoblast lineage cells

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Keiko [Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan); Ito, Masako [Medical Work-Life-Balance Center, Nagasaki University Hospital, Nagasaki 852-8501 (Japan); Naoe, Yoshinori [Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan); Lacy-Hulbert, Adam [Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114 (United States); Ikeda, Kyoji, E-mail: kikeda@ncgg.go.jp [Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan)

    2014-05-02

    Highlights: • Deletion of integrin αv in osteoblast lineage results in an impaired SOST response to loading in vivo. • c-Src–p130Cas–JNK–YAP/TAZ is activated via integrin αv on osteoblasts in response to FSS. • Deletion of integrin αv in osteoblasts results in impaired responses to mechanical stimulation. • Integrin αv is a key component of the mechanosensing machinery in bone. - Abstract: Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src–JNK–YAP/TAZ pathway in response to mechanical stimulation.

  15. Development of visible-light responsive and mechanically enhanced "smart" UCST interpenetrating network hydrogels.

    Science.gov (United States)

    Xu, Yifei; Ghag, Onkar; Reimann, Morgan; Sitterle, Philip; Chatterjee, Prithwish; Nofen, Elizabeth; Yu, Hongyu; Jiang, Hanqing; Dai, Lenore L

    2017-12-20

    An interpenetrating polymer network (IPN), chlorophyllin-incorporated environmentally responsive hydrogel was synthesized and exhibited the following features: enhanced mechanical properties, upper critical solution temperature (UCST) swelling behavior, and promising visible-light responsiveness. Poor mechanical properties are known challenges for hydrogel-based materials. By forming an interpenetrating network between polyacrylamide (PAAm) and poly(acrylic acid) (PAAc) polymer networks, the mechanical properties of the synthesized IPN hydrogels were significantly improved compared to hydrogels made of a single network of each polymer. The formation of the interpenetrating network was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), the analysis of glass transition temperature, and a unique UCST responsive swelling behavior, which is in contrast to the more prevalent lower critical solution temperature (LCST) behaviour of environmentally responsive hydrogels. The visible-light responsiveness of the synthesized hydrogel also demonstrated a positive swelling behavior, and the effect of incorporating chlorophyllin as the chromophore unit was observed to reduce the average pore size and further enhance the mechanical properties of the hydrogel. This interpenetrating network system shows potential to serve as a new route in developing "smart" hydrogels using visible-light as a simple, inexpensive, and remotely controllable stimulus.

  16. Integrin αv in the mechanical response of osteoblast lineage cells

    International Nuclear Information System (INIS)

    Kaneko, Keiko; Ito, Masako; Naoe, Yoshinori; Lacy-Hulbert, Adam; Ikeda, Kyoji

    2014-01-01

    Highlights: • Deletion of integrin αv in osteoblast lineage results in an impaired SOST response to loading in vivo. • c-Src–p130Cas–JNK–YAP/TAZ is activated via integrin αv on osteoblasts in response to FSS. • Deletion of integrin αv in osteoblasts results in impaired responses to mechanical stimulation. • Integrin αv is a key component of the mechanosensing machinery in bone. - Abstract: Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src–JNK–YAP/TAZ pathway in response to mechanical stimulation

  17. Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish.

    Science.gov (United States)

    Félix, Luís M; Serafim, Cindy; Valentim, Ana M; Antunes, Luís M; Matos, Manuela; Coimbra, Ana M

    2017-09-05

    Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages). Exposure at the 256-cell stage to ketamine induced an up-regulation of casp8 and pcna at 8 hpf while changes in pcna at the mRNA level were observed at 24 hpf. After the 50% epiboly stage exposure, the mRNA levels of casp9 were increased at 8 and 24 hpf while aifm1 was affected at 24 hpf. Both tp53 and pcna expressions were increased at 8 hpf. After exposure during the 1-4 somites stage, no meaningful changes on transcript levels were observed. The distribution of apoptotic cells and the caspase-like enzymatic activities of caspase-3 and -9 were not affected by ketamine exposure. It is proposed that ketamine exposure at the 256-cell stage induced a cooperative mechanism between proliferation and cellular death while following exposure at the 50% epiboly, a p53-dependent and -independent caspase activation may occur. Finally, at the 1-4 somites stage, the defence mechanisms are already fully in place to protect against ketamine-insult. Thus, ketamine teratogenicity seems to be dependent on the functional mechanisms present in each developmental stage. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Calmodulin Gene Expression in Response to Mechanical Wounding and Botrytis cinerea Infection in Tomato Fruit

    OpenAIRE

    Peng, Hui; Yang, Tianbao; Jurick, Wayne M.

    2014-01-01

    Calmodulin, a ubiquitous calcium sensor, plays an important role in decoding stress-triggered intracellular calcium changes and regulates the functions of numerous target proteins involved in various plant physiological responses. To determine the functions of calmodulin in fleshy fruit, expression studies were performed on a family of six calmodulin genes (SlCaMs) in mature-green stage tomato fruit in response to mechanical injury and Botrytis cinerea infection. Both wounding and pathogen in...

  19. Proteomic Insights into the Protective Mechanisms of an In Vitro Oxidative Stress Model of Early Stage Parkinson’s Disease

    OpenAIRE

    Bauereis, Brian; Haskins, William E.; LeBaron, Richard G.; Renthal, Robert

    2010-01-01

    Previous studies in Parkinson's disease (PD) models suggest that early events along the path to neurodegeneration involve activation of the ubiquitin-proteasome system (UPS), endoplasmic reticulum-associated degradation (ERAD), and the unfolded protein response (UPR) pathways, in both the sporadic and familial forms of the disease, and thus ER stress may be a common feature. Furthermore, impairments in protein degradation have been linked to oxidative stress as well as pathways associated wit...

  20. Natural variation in germination responses of Arabidopsis to seasonal cues and their associated physiological mechanisms

    Science.gov (United States)

    Barua, Deepak; Butler, Colleen; Tisdale, Tracy E.; Donohue, Kathleen

    2012-01-01

    Background and Aims Despite the intense interest in phenological adaptation to environmental change, the fundamental character of natural variation in germination is almost entirely unknown. Specifically, it is not known whether different genotypes within a species are germination specialists to particular conditions, nor is it known what physiological mechanisms of germination regulation vary in natural populations and how they are associated with responses to particular environmental factors. Methods We used a set of recombinant inbred genotypes of Arabidopsis thaliana, in which linkage disequilibrium has been disrupted over seven generations, to test for genetic variation and covariation in germination responses to distinct environmental factors. We then examined physiological mechanisms associated with those responses, including seed-coat permeability and sensitivity to the phytohormones gibberellic acid (GA) and abscisic acid (ABA). Key Results Genetic variation for germination was environment-dependent, but no evidence for specialization of germination to different conditions was found. Hormonal sensitivities also exhibited significant genetic variation, but seed-coat properties did not. GA sensitivity was associated with germination responses to multiple environmental factors, but seed-coat permeability and ABA sensitivity were associated with specific germination responses, suggesting that an evolutionary change in GA sensitivity could affect germination in multiple environments, but that of ABA sensitivity may affect germination under more restricted conditions. Conclusions The physiological mechanisms of germination responses to specific environmental factors therefore can influence the ability to adapt to diverse seasonal environments encountered during colonization of new habitats or with future predicted climate change. PMID:22012958

  1. Response of the human tympanic membrane to transient acoustic and mechanical stimuli: Preliminary results

    Science.gov (United States)

    Razavi, Payam; Ravicz, Michael E.; Dobrev, Ivo; Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.

    2016-01-01

    The response of the tympanic membrane (TM) to transient environmental sounds and the contributions of different parts of the TM to middle-ear sound transmission were investigated by measuring the TM response to global transients (acoustic clicks) and to local transients (mechanical impulses) applied to the umbo and various locations on the TM. A lightly-fixed human temporal bone was prepared by removing the ear canal, inner ear, and stapes, leaving the incus, malleus, and TM intact. Motion of nearly the entire TM was measured by a digital holography system with a high speed camera at a rate of 42 000 frames per second, giving a temporal resolution of <24 μs for the duration of the TM response. The entire TM responded nearly instantaneously to acoustic transient stimuli, though the peak displacement and decay time constant varied with location. With local mechanical transients, the TM responded first locally at the site of stimulation, and the response spread approximately symmetrically and circumferentially around the umbo and manubrium. Acoustic and mechanical transients provide distinct and complementary stimuli for the study of TM response. Spatial variations in decay and rate of spread of response imply local variations in TM stiffness, mass, and damping. PMID:26880098

  2. Mechanical response and buckling of a polymer simulation model of the cell nucleus

    Science.gov (United States)

    Banigan, Edward; Stephens, Andrew; Marko, John

    The cell nucleus must robustly resist extra- and intracellular forces to maintain genome architecture. Micromanipulation experiments measuring nuclear mechanical response reveal that the nucleus has two force response regimes: a linear short-extension response due to the chromatin interior and a stiffer long-extension response from lamin A, comprising the intermediate filament protein shell. To explain these results, we developed a quantitative simulation model with realistic parameters for chromatin and the lamina. Our model predicts that crosslinking between chromatin and the lamina is essential for responding to small strains and that changes to the interior topological organization can alter the mechanical response of the whole nucleus. Thus, chromatin polymer elasticity, not osmotic pressure, is the dominant regulator of this force response. Our model reveals a novel buckling transition for polymer shells: as force increases, the shell buckles transverse to the applied force. This transition, which arises from topological constrains in the lamina, can be mitigated by tuning the properties of the chromatin interior. Thus, we find that the genome is a resistive mechanical element that can be tuned by its organization and connectivity to the lamina.

  3. The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

    Science.gov (United States)

    Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

    2015-05-15

    The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Electro-chemo-mechanical response of a free-standing polypyrrole strip

    International Nuclear Information System (INIS)

    Vazquez, G; Otero, T F; Cascales, J J L

    2008-01-01

    Further development of mechanical devices based on conducting polymers; require a precise understanding of their mechanical response, i.e. their control, under a controlled external current. In this work, we show some results for the relation between the electrical current consumed in the electrochemical process and the mechanical work developed by a freestanding polypyrrole strip, when it is subjected to a stretching force (stress). Under these conditions, from the results obtained in this work, we observe how it results almost impossible to predict a straight relationship between mechanical work and current consumed in the electrochemical process. In addition, we will quantify the variation of the mechanical properties of the free standing polypyrrole strip associated with the oxidation state of the polymer by measuring its Young's modulus.

  5. Electro-chemo-mechanical response of a free-standing polypyrrole strip

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez, G; Otero, T F; Cascales, J J L [Centra de ElectroquImica y Materiales Inteligentes (CEMI), Universidad Politecnica de Cartagena, Cartagena 30203, Murcia (Spain)], E-mail: javier.lopez@upct.es

    2008-08-15

    Further development of mechanical devices based on conducting polymers; require a precise understanding of their mechanical response, i.e. their control, under a controlled external current. In this work, we show some results for the relation between the electrical current consumed in the electrochemical process and the mechanical work developed by a freestanding polypyrrole strip, when it is subjected to a stretching force (stress). Under these conditions, from the results obtained in this work, we observe how it results almost impossible to predict a straight relationship between mechanical work and current consumed in the electrochemical process. In addition, we will quantify the variation of the mechanical properties of the free standing polypyrrole strip associated with the oxidation state of the polymer by measuring its Young's modulus.

  6. Mechanical characterization of raw material quality and its implication for Early Upper Palaeolithic Moravia

    Czech Academy of Sciences Publication Activity Database

    Monik, M.; Hadraba, Hynek

    2016-01-01

    Roč. 425, DEC (2016), s. 425-436 ISSN 1040-6182 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081723 Keywords : Charpy impact test * Microhardness * Early Upper Palaeolithic * Moravia * Lithics Subject RIV: JH - Ceramics, Fire-Resistant Materials and Glass Impact factor: 2.199, year: 2016

  7. High fidelity computational characterization of the mechanical response of thermally aged polycarbonate

    Science.gov (United States)

    Zhang, Zesheng; Zhang, Lili; Jasa, John; Li, Wenlong; Gazonas, George; Negahban, Mehrdad

    2017-07-01

    A representative all-atom molecular dynamics (MD) system of polycarbonate (PC) is built and conditioned to capture and predict the behaviours of PC in response to a broad range of thermo-mechanical loadings for various thermal aging. The PC system is constructed to have a distribution of molecular weights comparable to a widely used commercial PC (LEXAN 9034), and thermally conditioned to produce models for aged and unaged PC. The MD responses of these models are evaluated through comparisons to existing experimental results carried out at much lower loading rates, but done over a broad range of temperatures and loading modes. These experiments include monotonic extension/compression/shear, unilaterally and bilaterally confined compression, and load-reversal during shear. It is shown that the MD simulations show both qualitative and quantitative similarity with the experimental response. The quantitative similarity is evaluated by comparing the dilatational response under bilaterally confined compression, the shear flow viscosity and the equivalent yield stress. The consistency of the in silico response to real laboratory experiments strongly suggests that the current PC models are physically and mechanically relevant and potentially can be used to investigate thermo-mechanical response to loading conditions that would not easily be possible. These MD models may provide valuable insight into the molecular sources of certain observations, and could possibly offer new perspectives on how to develop constitutive models that are based on better understanding the response of PC under complex loadings. To this latter end, the models are used to predict the response of PC to complex loading modes that would normally be difficult to do or that include characteristics that would be difficult to measure. These include the responses of unaged and aged PC to unilaterally confined extension/compression, cyclic uniaxial/shear loadings, and saw-tooth extension/compression/shear.

  8. Early and late nasal symptom response to allergen challenge. The effect of pretreatment with a glucocorticosteroid spray

    DEFF Research Database (Denmark)

    Grønborg, H; Bisgaard, H; Rømeling, Frans

    1993-01-01

    We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment with the glucocor......We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment....... These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72......% reduction; P effect on discharge (37% reduction; P effect on blockage (17% reduction of nasal inspiratory peak flow rate; P effect on the initial early response. The effect on the late...

  9. Correlation of transcriptomic responses and metal bioaccumulation in Mytilus edulis L. reveals early indicators of stress

    Energy Technology Data Exchange (ETDEWEB)

    Poynton, Helen C., E-mail: helen.poynton@umb.edu; Robinson, William E.; Blalock, Bonnie J.; Hannigan, Robyn E.

    2014-10-15

    , three transcripts directly involved in the unfolded protein response (UPR) were induced in the metal treatments at 2 weeks and were further up-regulated at 4 weeks. Overall, correlation of tissue concentrations and gene expression responses indicates that as mussels accumulate higher concentrations of metals, initial stress responses are mobilized to protect tissues. However, given the role of UPR in apoptosis, it serves as an early indicator of stress, which once overwhelmed will result in adverse physiological effects.

  10. How Streptomyces anulatus Primes Grapevine Defenses to Cope with Gray Mold: A Study of the Early Responses of Cell Suspensions

    Directory of Open Access Journals (Sweden)

    Parul Vatsa-Portugal

    2017-06-01

    Full Text Available Gray mold, caused by Botrytis cinerea, is one of the most destructive diseases of grapevine and is controlled with an intense application of fungicides. As alternatives to chemicals, beneficial microbes may promote plant health by stimulating the plant’s immune system. An actinomycete, Streptomyces anulatus S37, has been screened from the rhizosphere microbiome of healthy Vitis vinifera on the basis of its ability to promote grapevine growth and to induce resistance against various phytopathogens, including B. cinerea. However, molecular mechanisms involved locally after direct perception of these bacteria by plant cells still remain unknown. This study focuses on local defense events induced in grapevine cells during interactions with S. anulatus S37 before and after pathogen challenge. We demonstrated that S. anulatus S37 induced early responses including oxidative burst, extracellular alkalinization, activation of protein kinases, induction of defense gene expression and phytoalexin accumulation, but not the programmed cell death. Interestingly, upon challenge with the B. cinerea, the S. anulatus S37 primed grapevine cells for enhanced defense reactions with a decline in cell death. In the presence of the EGTA, a calcium channel inhibitor, the induced oxidative burst, and the protein kinase activity were inhibited, but not the extracellular alkalinization, suggesting that Ca2+ may also contribute upstream to the induced defenses. Moreover, desensitization assays using extracellular pH showed that once increased by S. anulatus S37, cells became refractory to further stimulation by B. cinerea, suggesting that grapevine cells perceive distinctly beneficial and pathogenic microbes.

  11. Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1.

    Directory of Open Access Journals (Sweden)

    Karine Z Oben

    Full Text Available An understanding of how each individual 5q chromosome critical deleted region (CDR gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs. Early Growth Response 1 (EGR1 is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell quiescence as well as the master regulator of apoptosis-p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies.

  12. Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

    Science.gov (United States)

    Byrne, N. G.; Muir, T. C.

    1985-01-01

    The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is

  13. Understory vegetation response to mechanical mastication and other fuels treatments in a ponderosa pine forest

    Science.gov (United States)

    Jeffrey M. Kane; J. Morgan Varner; Eric E. Knapp

    2010-01-01

    Questions: What influence does mechanical mastication and other fuel treatments have on: (1) canopy and forest floor response variables that influence understory plant development; (2) initial understory vegetation cover, diversity, and composition; and (3) shrub and non-native species density in a secondgrowth ponderosa pine forest....

  14. Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid

    OpenAIRE

    Drewes, Asbjorn Mohr; Reddy, Hariprasad; Staahl, Camilla; Pedersen, Jan; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans

    2005-01-01

    AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.

  15. Reactive Molecular Dynamics Simulations to Understand Mechanical Response of Thaumasite under Temperature and Strain Rate Effects.

    Science.gov (United States)

    Hajilar, Shahin; Shafei, Behrouz; Cheng, Tao; Jaramillo-Botero, Andres

    2017-06-22

    Understanding the structural, thermal, and mechanical properties of thaumasite is of great interest to the cement industry, mainly because it is the phase responsible for the aging and deterioration of civil infrastructures made of cementitious materials attacked by external sources of sulfate. Despite the importance, effects of temperature and strain rate on the mechanical response of thaumasite had remained unexplored prior to the current study, in which the mechanical properties of thaumasite are fully characterized using the reactive molecular dynamics (RMD) method. With employing a first-principles based reactive force field, the RMD simulations enable the description of bond dissociation and formation under realistic conditions. From the stress-strain curves of thaumasite generated in the x, y, and z directions, the tensile strength, Young's modulus, and fracture strain are determined for the three orthogonal directions. During the course of each simulation, the chemical bonds undergoing tensile deformations are monitored to reveal the bonds responsible for the mechanical strength of thaumasite. The temperature increase is found to accelerate the bond breaking rate and consequently the degradation of mechanical properties of thaumasite, while the strain rate only leads to a slight enhancement of them for the ranges considered in this study.

  16. Computational methods for describing the laser-induced mechanical response of tissue

    Energy Technology Data Exchange (ETDEWEB)

    Trucano, T.; McGlaun, J.M.; Farnsworth, A.

    1994-02-01

    Detailed computational modeling of laser surgery requires treatment of the photoablation of human tissue by high intensity pulses of laser light and the subsequent thermomechanical response of the tissue. Three distinct physical regimes must be considered to accomplish this: (1) the immediate absorption of the laser pulse by the tissue and following tissue ablation, which is dependent upon tissue light absorption characteristics; (2) the near field thermal and mechanical response of the tissue to this laser pulse, and (3) the potential far field (and longer time) mechanical response of witness tissue. Both (2) and (3) are dependent upon accurate constitutive descriptions of the tissue. We will briefly review tissue absorptivity and mechanical behavior, with an emphasis on dynamic loads characteristic of the photoablation process. In this paper our focus will center on the requirements of numerical modeling and the uncertainties of mechanical tissue behavior under photoablation. We will also discuss potential contributions that computational simulations can make in the design of surgical protocols which utilize lasers, for example, in assessing the potential for collateral mechanical damage by laser pulses.

  17. Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat

    International Nuclear Information System (INIS)

    Takahashi, Akihisa; Ohnishi, Takeo

    2009-01-01

    Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat. (author)

  18. Response of primiparous and multiparous buffaloes to yeast culture supplementation during early and mid-lactation

    Directory of Open Access Journals (Sweden)

    Hanne H. Hansen

    2017-12-01

    Full Text Available Strains of live Saccharomyces cerevisiae yeast have exhibited probiotic effects in ruminants. This study investigated the effects of the dietary yeast supplement, S. cerevisiae (Yea-Sacc1026, on primiparous (PP and multiparous (MP Egyptian buffaloes in early to mid-lactation. Lactating buffaloes were fed either a basal total mixed ration (TMR, control; 4 PP and 8 MP or the basal TMR plus 10 g Yea-Sacc1026 per buffalo cow per day (yeast; 4 PP and 8 MP. The feeds were given from 15 days prepartum to 180 days postpartum. Feed intake, body weight, and milk yields (MY were recorded, and milk and blood samples were collected for analyses. Feces were collected from days 45 to 47 during early lactation and from days 90 to 92 during mid-lactation to determine apparent digestibility of dry matter (DM, organic matter (OM, crude protein (CP and crude fiber (CF. Energy corrected milk yield (ECM, feed conversion, and energy and nitrogen conversion efficiency were calculated. Yeast treated MP buffaloes consumed more DM (P ≤ 0.041 and CP than the untreated control group. Apparent digestibility of DM and OM were significantly greater at mid-lactation for treated versus control group (P = 0.001. Crude fiber digestibility was greater in MP than in PP buffaloes (P = 0.049, and yeast supplemented MP cows had a greater CF digestibility than control MP buffaloes at mid-lactation (P = 0.010. Total blood lipids decreased after yeast supplementation (P = 0.029. Milk yields, ECM, fat and protein yields increased for yeast treated MP buffaloes (P ≤ 0.039. The study concluded that the response to yeast supplementation in buffalo cows is parity dependent. Multiparous buffaloes respond to yeast supplementation with an increased DM intake and CF digestibility without significant weight gains, allowing a greater ECM yield with less fat mobilization. Supplementing buffaloes with yeast culture may increase milk production in early lactation and results in a

  19. Nonlinear mechanical response of the extracellular matrix: learning from articular cartilage

    Science.gov (United States)

    Kearns, Sarah; Das, Moumita

    2015-03-01

    We study the mechanical structure-function relations in the extracellular matrix (ECM) with focus on nonlinear shear and compression response. As a model system, our study focuses on the ECM in articular cartilage tissue which has two major mechanobiological components: a network of the biopolymer collagen that acts as a stiff, reinforcing matrix, and a flexible aggrecan network that facilitates deformability. We model this system as a double network hydrogel made of interpenetrating networks of stiff and flexible biopolymers respectively. We study the linear and nonlinear mechanical response of the model ECM to shear and compression forces using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings.

  20. Transcriptomic responses to darkness stress point to common coral bleaching mechanisms

    Science.gov (United States)

    Desalvo, M. K.; Estrada, A.; Sunagawa, S.; Medina, Mónica

    2012-03-01

    Coral bleaching occurs in response to numerous abiotic stressors, the ecologically most relevant of which is hyperthermic stress due to increasing seawater temperatures. Bleaching events can span large geographic areas and are currently a salient threat to coral reefs worldwide. Much effort has been focused on understanding the molecular and cellular events underlying bleaching, and these studies have mainly utilized heat and light stress regimes. In an effort to determine whether different stressors share common bleaching mechanisms, we used complementary DNA (cDNA) microarrays for the corals Acropora palmata and Montastraea faveolata (containing >10,000 features) to measure differential gene expression during darkness stress. Our results reveal a striking transcriptomic response to darkness in A. palmata involving chaperone and antioxidant up-regulation, growth arrest, and metabolic modifications. As these responses were previously measured during thermal stress, our results suggest that different stressors may share common bleaching mechanisms. Furthermore, our results point to hypoxia and endoplasmic reticulum stress as critical cellular events involved in molecular bleaching mechanisms. On the other hand, we identified a meager transcriptomic response to darkness in M. faveolata where gene expression differences between host colonies and sampling locations were greater than differences between control and stressed fragments. This and previous coral microarray studies reveal the immense range of transcriptomic responses that are possible when studying two coral species that differ greatly in their ecophysiology, thus pointing to the importance of comparative approaches in forecasting how corals will respond to future environmental change.

  1. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    Directory of Open Access Journals (Sweden)

    Xu Yu-Dong

    2010-08-01

    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

  2. Comparative transcriptome analysis of two rice varieties in response to rice stripe virus and small brown planthoppers during early interaction.

    Directory of Open Access Journals (Sweden)

    Wenjing Zheng

    Full Text Available Rice stripe, a virus disease, transmitted by a small brown planthopper (SBPH, has greatly reduced production of japonica rice in East Asia, especially in China. Although we have made great progress in mapping resistance genes, little is known about the mechanism of resistance. By de novo transcriptome assembling, we gained sufficient transcript data to analyze changes in gene expression of early interaction in response to SBPH and RSV infection in rice. Respectively 648 and 937 DEGs were detected from the disease-resistant (Liaonong 979 and the susceptible (Fengjin varieties, most of which were up-regulated. We found 37 genes related to insect resistance, which mainly included genes for jasmonate-induced protein, TIFY protein, lipoxygenase, as well as trypsin inhibitor genes and transcription factor genes. In the interaction process between RSV and rice, 87 genes were thought to be related to RSV resistance; these primarily included 12 peroxidase biosynthesis genes, 12 LRR receptor-like protein kinase genes, 6 genes coding pathogenesis-related proteins, 4 glycine-rich cell wall structural protein genes, 2 xyloglucan hydrolase genes and a cellulose synthase. The results indicate that the rice-pathogen interaction happened both in disease-resistant and susceptible varieties, and some genes related to JA biosynthesis played key roles in the interaction between SBPHs and rice. When rice was infected by RSV a hypersensitive reaction (HR in the disease-resistant variety was suppressed, which resulted from an increase in peroxidase expression and down-regulation of LRR receptor-like protein kinase and pathogenesis-related proteins, while, the changes of peroxidase biosynthesis, glycine-rich cell wall structural protein, cellulose synthase and xyloglucan endotransglucosylase/hydrolase could lead to the strengthening of physical barriers of rice, which may be an important resistance mechanism to RSV in rice.

  3. Comparative transcriptome analysis of two rice varieties in response to rice stripe virus and small brown planthoppers during early interaction.

    Science.gov (United States)

    Zheng, Wenjing; Ma, Li; Zhao, Jiaming; Li, Zhiqiang; Sun, Fuyu; Lu, Xiaochun

    2013-01-01

    Rice stripe, a virus disease, transmitted by a small brown planthopper (SBPH), has greatly reduced production of japonica rice in East Asia, especially in China. Although we have made great progress in mapping resistance genes, little is known about the mechanism of resistance. By de novo transcriptome assembling, we gained sufficient transcript data to analyze changes in gene expression of early interaction in response to SBPH and RSV infection in rice. Respectively 648 and 937 DEGs were detected from the disease-resistant (Liaonong 979) and the susceptible (Fengjin) varieties, most of which were up-regulated. We found 37 genes related to insect resistance, which mainly included genes for jasmonate-induced protein, TIFY protein, lipoxygenase, as well as trypsin inhibitor genes and transcription factor genes. In the interaction process between RSV and rice, 87 genes were thought to be related to RSV resistance; these primarily included 12 peroxidase biosynthesis genes, 12 LRR receptor-like protein kinase genes, 6 genes coding pathogenesis-related proteins, 4 glycine-rich cell wall structural protein genes, 2 xyloglucan hydrolase genes and a cellulose synthase. The results indicate that the rice-pathogen interaction happened both in disease-resistant and susceptible varieties, and some genes related to JA biosynthesis played key roles in the interaction between SBPHs and rice. When rice was infected by RSV a hypersensitive reaction (HR) in the disease-resistant variety was suppressed, which resulted from an increase in peroxidase expression and down-regulation of LRR receptor-like protein kinase and pathogenesis-related proteins, while, the changes of peroxidase biosynthesis, glycine-rich cell wall structural protein, cellulose synthase and xyloglucan endotransglucosylase/hydrolase could lead to the strengthening of physical barriers of rice, which may be an important resistance mechanism to RSV in rice.

  4. CT Perfusion for Early Response Evaluation of Radiofrequency Ablation of Focal Liver Lesions: First Experience

    Energy Technology Data Exchange (ETDEWEB)

    Marquez, Herman P., E-mail: hermanpaulo.marquezmasquiaran@usz.ch; Puippe, Gilbert; Mathew, Rishi Philip; Alkadhi, Hatem; Pfammatter, Thomas; Fischer, Michael A. [University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Institute of Diagnostic and Interventional Radiology (Switzerland)

    2017-01-15

    PurposeTo investigate the value of perfusion CT (P-CT) for early assessment of treatment response in patients undergoing radiofrequency ablation (RFA) of focal liver lesions.Methods and Materials20 consecutive patients (14 men; mean age 64 ± 14) undergoing P-CT within 24 h after RFA of liver metastases (n = 10) or HCC (n = 10) were retrospectively included. Two readers determined arterial liver perfusion (ALP, mL/min/100 mL), portal liver perfusion (PLP, mL/min/100 mL), and hepatic perfusion index (HPI, %) in all post-RFA lesions by placing a volume of interest in the necrotic central (CZ), the transition (TZ), and the surrounding parenchymal (PZ) zone. Patients were classified into complete responders (no residual tumor) and incomplete responders (residual/progressive tumor) using imaging follow-up with contrast-enhanced CT or MRI after a mean of 57 ± 30 days. Prediction of treatment response was evaluated using the area under the curve (AUC) from receiver operating characteristic analysis.ResultsMean ALP/PLP/HPI of both readers were 4.8/15.4/61.2 for the CZ, 9.9/16.8/66.3 for the TZ and 20.7/29.0/61.8 for the PZ. Interreader agreement of HPI was fair for the CZ (intraclass coefficient 0.713), good for the TZ (0.813), and excellent for the PZ (0.920). For both readers, there were significant differences in HPI of the CZ and TZ between responders and nonresponders (both, P < 0.05). HPI of the TZ showed the highest AUC (0.911) for prediction of residual tumor, suggesting a cut-off value of 76 %.ConclusionIncreased HPI of the transition zone assessed with P-CT after RFA might serve as an early quantitative biomarker for residual tumor in patients with focal liver lesions.

  5. New Insight in Understanding the mechanical responses of polymer glasses using molecular dynamic simulation

    Science.gov (United States)

    Zheng, Yexin; Wang, Shi-Qing; Tsige, Mesfin

    The Kremer-Grest bead-spring model has been the standard model in molecular dynamics simulation of polymer glasses. However, due to current computational limitations in accessing relevant time scales in polymer glasses in a reasonable amount of CPU time, simulation of mechanical response of polymer glasses in molecular dynamic simulations requires a much higher quenching rate and deformation rate than used in experiments. Despite several orders of magnitude difference in time scale between simulation and experiment, previous studies have shown that simulations can produce meaningful results that can be directly compared with experimental results. In this work we show that by tuning the quenching rate and deformation rate relative to the segmental relaxation times, a reasonable mechanical response shows up in the glassy state. Specifically, we show a younger glass prepared with a faster quenching rate shows glassy responses only when the imposed deformation rate is proportionally higher. the National Science Foundation (DMR-1444859 and DMR-1609977).

  6. Nonlinear dynamic response of electro-thermo-mechanically loaded piezoelectric cylindrical shell reinforced with BNNTs

    International Nuclear Information System (INIS)

    Yang, J H; Yang, J; Kitipornchai, S

    2012-01-01

    This paper presents an investigation on the nonlinear dynamic response of piezoelectric cylindrical shells reinforced with boron nitride nanotubes (BNNTs) under a combined axisymmetric electro-thermo-mechanical loading. By employing the classical Donnell shell theory, the von Kármán–Donnell kinematic relationship, and a piezo-elastic constitutive law including thermal effects, the nonlinear governing equations of motion of the shell are derived through the Reissner variational principle. The finite difference method and a time-integration scheme are used to obtain the nonlinear dynamic response of the BNNT-reinforced piezoelectric shell. A parametric study is conducted, showing the effects of geometrically nonlinear deformation, applied voltage, temperature change, mechanical load, BNNT volume fraction and boundary conditions on the nonlinear dynamic response. (paper)

  7. Perspectives on deciphering mechanisms underlying plant heat stress response and thermotolerance

    Directory of Open Access Journals (Sweden)

    Kamila Lucia Bokszczanin

    2013-08-01

    Full Text Available Global warming is a major threat for agriculture and food safety and in many cases the negative effects are already apparent. The current challenge of basic and applied plant science is to decipher the molecular mechanisms of heat stress response and thermotolerance in detail and use this information to identify genotypes that will withstand unfavorable environmental conditions. Nowadays X-omics approaches complement the findings of previous targeted studies and highlight the complexity of heat stress response mechanisms giving information for so far unrecognized genes, proteins and metabolites as potential key players of thermotolerance. Even more, roles of epigenetic mechanisms and the involvement of small RNAs in thermotolerance are currently emerging and thus open new directions of yet unexplored areas of plant heat stress response. In parallel it is emerging that although the whole plant is vulnerable to heat, specific organs are particularly sensitive to elevated temperatures. This has redirected research from the vegetative to generative tissues. The sexual reproduction phase is considered as the most sensitive to heat and specifically pollen exhibits the highest sensitivity and frequently an elevation of the temperature just a few degrees above the optimum during pollen development can have detrimental effects for crop production. Compared to our knowledge on heat stress response of vegetative tissues, the information on pollen is still scarce. Nowadays, several techniques for high-throughput X-omics approaches provide major tools to explore the principles of pollen heat stress response and thermotolerance mechanisms in specific genotypes. The collection of such information will provide an excellent support for improvement of breeding programs to facilitate the development of tolerant cultivars. The review aims at describing the current knowledge of thermotolerance mechanisms and the technical advances which will foster new insights into

  8. Functional weight-bearing mobilization after Achilles tendon rupture enhances early healing response: a single-blinded randomized controlled trial.

    Science.gov (United States)

    Valkering, Kars P; Aufwerber, Susanna; Ranuccio, Francesco; Lunini, Enricomaria; Edman, Gunnar; Ackermann, Paul W

    2017-06-01

    Functional weight-bearing mobilization may improve repair of Achilles tendon rupture (ATR), but the underlying mechanisms and outcome were unknown. We hypothesized that functional weight-bearing mobilization by means of increased metabolism could improve both early and long-term healing. In this prospective randomized controlled trial, patients with acute ATR were randomized to either direct post-operative functional weight-bearing mobilization (n = 27) in an orthosis or to non-weight-bearing (n = 29) plaster cast immobilization. During the first two post-operative weeks, 15°-30° of plantar flexion was allowed and encouraged in the functional weight-bearing mobilization group. At 2 weeks, patients in the non-weight-bearing cast immobilization group received a stiff orthosis, while the functional weight-bearing mobilization group continued with increased range of motion. At 6 weeks, all patients discontinued immobilization. At 2 weeks, healing metabolites and markers of procollagen type I (PINP) and III (PIIINP) were examined using microdialysis. At 6 and 12 months, functional outcome using heel-rise test was assessed. Healing tendons of both groups exhibited increased levels of metabolites glutamate, lactate, pyruvate, and of PIIINP (all p bearing mobilization group demonstrated significantly higher concentrations of glutamate compared to the non-weight-bearing cast immobilization group (p = 0.045).The upregulated glutamate levels were significantly correlated with the concentrations of PINP (r = 0.5, p = 0.002) as well as with improved functional outcome at 6 months (r = 0.4; p = 0.014). Heel-rise tests at 6 and 12 months did not display any differences between the two groups. Functional weight-bearing mobilization enhanced the early healing response of ATR. In addition, early ankle range of motion was improved without the risk of Achilles tendon elongation and without altering long-term functional outcome. The relationship between

  9. Self-focused and other-focused resiliency: Plausible mechanisms linking early family adversity to health problems in college women.

    Science.gov (United States)

    Coleman, Sulamunn R M; Zawadzki, Matthew J; Heron, Kristin E; Vartanian, Lenny R; Smyth, Joshua M

    2016-01-01

    This study examined whether self-focused and other-focused resiliency help explain how early family adversity relates to perceived stress, subjective health, and health behaviors in college women. Female students (N = 795) participated between October 2009 and May 2010. Participants completed self-report measures of early family adversity, self-focused (self-esteem, personal growth initiative) and other-focused (perceived social support, gratitude) resiliency, stress, subjective health, and health behaviors. Using structural equation modeling, self-focused resiliency associated with less stress, better subjective health, more sleep, less smoking, and less weekend alcohol consumption. Other-focused resiliency associated with more exercise, greater stress, and more weekend alcohol consumption. Early family adversity was indirectly related to all health outcomes, except smoking, via self-focused and other-focused resiliency. Self-focused and other-focused resiliency represent plausible mechanisms through which early family adversity relates to stress and health in college women. This highlights areas for future research in disease prevention and management.

  10. Maternal buffering beyond glucocorticoids: impact of early life stress on corticolimbic circuits that control infant responses to novelty

    Science.gov (United States)

    Howell, Brittany R.; McMurray, Matthew S.; Guzman, Dora B.; Nair, Govind; Shi, Yundi; McCormack, Kai M.; Hu, Xiaoping; Styner, Martin A.; Sanchez, Mar M.

    2017-01-01

    Maternal presence has a potent buffering effect on infant fear and stress responses in primates. We previously reported that maternal presence is not effective in buffering the endocrine stress response in infant rhesus monkeys reared by maltreating mothers. We have also reported that maltreating mothers show low maternal responsiveness and permissiveness/secure-base behavior. Although still not understood, it is possible that this maternal buffering effect is mediated, at least partially, through deactivation of amygdala response circuits when mothers are present. Here we studied rhesus monkey infants that differed in the quality of early maternal care to investigate how this early experience modulated maternal buffering effects on behavioral responses to novelty during the weaning period. We also examined the relationship between these behavioral responses and structural connectivity in one of the underlying regulatory neural circuits: amygdala-prefrontal pathways. Our findings suggest that infant exploration in a novel situation is predicted by maternal responsiveness and structural integrity of amygdala-prefrontal white matter depending on maternal presence (positive relationships when mother is absent). These results provide evidence that maternal buffering of infant behavioral inhibition is dependent on the quality of maternal care and structural connectivity of neural pathways that are sensitive to early life stress. PMID:27295326

  11. Responses of Nucleus Tractus Solitarius (NTS) early and late neurons to blood pressure changes in anesthetized F344 rats.

    Science.gov (United States)

    Kolpakova, Jenya; Li, Liang; Hatcher, Jeffrey T; Gu, He; Zhang, Xueguo; Chen, Jin; Cheng, Zixi Jack

    2017-01-01

    Previously, many different types of NTS barosensitive neurons were identified. However, the time course of NTS barosensitive neuronal activity (NA) in response to arterial pressure (AP) changes, and the relationship of NA-AP changes, have not yet been fully quantified. In this study, we made extracellular recordings of single NTS neurons firing in response to AP elevation induced by occlusion of the descending aorta in anesthetized rats. Our findings were that: 1) Thirty-five neurons (from 46 neurons) increased firing, whereas others neurons either decreased firing upon AP elevation, or were biphasic: first decreased firing upon AP elevation and then increased firing during AP decrease. 2) Fourteen neurons with excitatory responses were activated and rapidly increased their firing during the early phase of AP increase (early neurons); whereas 21 neurons did not increase firing until the mean arterial pressure changes (ΔMAP) reached near/after the peak (late neurons). 3) The early neurons had a significantly higher firing rate than late neurons during AP elevation at a similar rate. 4) Early neuron NA-ΔMAP relationship could be well fitted and characterized by the sigmoid logistic function with the maximal gain of 29.3. 5) The increase of early NA correlated linearly with the initial heart rate (HR) reduction. 6) The late neurons did not contribute to the initial HR reduction. However, the late NA could be well correlated with HR reduction during the late phase. Altogether, our study demonstrated that the NTS excitatory neurons could be grouped into early and late neurons based on their firing patterns. The early neurons could be characterized by the sigmoid logistic function, and different neurons may differently contribute to HR regulation. Importantly, the grouping and quantitative methods used in this study may provide a useful tool for future assessment of functional changes of early and late neurons in disease models.

  12. Early stages of the mechanical alloying of TiC–TiN powder mixtures

    International Nuclear Information System (INIS)

    Mura, Giovanna; Musu, Elodia; Delogu, Francesco

    2013-01-01

    The present work focuses on the alloying behavior of TiC–TiN powder mixtures submitted to mechanical processing by ball milling. Accurate X-ray diffraction analyses indicate a progressive modification of the unit cell parameters of the TiC and TiN phases, suggesting the formation of TiC- and TiN-rich solid solutions with an increasingly larger content of solutes. Once the discrete character of the mechanical treatment is taken into due account, the smooth change of the unit cell parameters can be explained by a sequence of mutual dissolution stages related to individual collisions. At each collision, the average chemical composition of small amounts of TiC- and TiN-rich phases changes discontinuously. The discontinuous changes can be tentatively ascribed to local mass transport processes activated by the mechanical deformation of powders at collisions. -- Highlights: ► Mechanically processed TiC–TiN powder mixtures form two solid solutions. ► An analytical model was developed to describe the mechanical alloying kinetics. ► The amount of powder alloyed at collision was indirectly estimated. ► A few nanomoles of material participate in the alloying process at each collision. ► The chemical composition of the solid solutions was shown to change discontinuously.

  13. Early stages of the mechanical alloying of TiC-TiN powder mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Mura, Giovanna [Dipartimento di Ingegneria Elettrica ed Elettronica, Universita degli Studi di Cagliari, via Marengo 2, 09123 Cagliari (Italy); Musu, Elodia [Industrial Telemicroscopy Laboratory, Sardegna Ricerche, Polaris, Technology Park of Sardinia, Edificio 3, Loc. Piscinamanna, 09010 Pula (Italy); Delogu, Francesco, E-mail: francesco.delogu@dimcm.unica.it [Dipartimento di Ingegneria Meccanica, Chimica, e dei Materiali, Universita degli Studi di Cagliari, via Marengo 2, I-09123 Cagliari (Italy)

    2013-01-15

    The present work focuses on the alloying behavior of TiC-TiN powder mixtures submitted to mechanical processing by ball milling. Accurate X-ray diffraction analyses indicate a progressive modification of the unit cell parameters of the TiC and TiN phases, suggesting the formation of TiC- and TiN-rich solid solutions with an increasingly larger content of solutes. Once the discrete character of the mechanical treatment is taken into due account, the smooth change of the unit cell parameters can be explained by a sequence of mutual dissolution stages related to individual collisions. At each collision, the average chemical composition of small amounts of TiC- and TiN-rich phases changes discontinuously. The discontinuous changes can be tentatively ascribed to local mass transport processes activated by the mechanical deformation of powders at collisions. -- Highlights: Black-Right-Pointing-Pointer Mechanically processed TiC-TiN powder mixtures form two solid solutions. Black-Right-Pointing-Pointer An analytical model was developed to describe the mechanical alloying kinetics. Black-Right-Pointing-Pointer The amount of powder alloyed at collision was indirectly estimated. Black-Right-Pointing-Pointer A few nanomoles of material participate in the alloying process at each collision. Black-Right-Pointing-Pointer The chemical composition of the solid solutions was shown to change discontinuously.

  14. Evidence for an early innate immune response in the motor cortex of ALS.

    Science.gov (United States)

    Jara, Javier H; Genç, Barış; Stanford, Macdonell J; Pytel, Peter; Roos, Raymond P; Weintraub, Sandra; Mesulam, M Marsel; Bigio, Eileen H; Miller, Richard J; Özdinler, P Hande

    2017-06-26

    Recent evidence indicates the importance of innate immunity and neuroinflammation with microgliosis in amyotrophic lateral sclerosis (ALS) pathology. The MCP1 (monocyte chemoattractant protein-1) and CCR2 (CC chemokine receptor 2) signaling system has been strongly associated with the innate immune responses observed in ALS patients, but the motor cortex has not been studied in detail. After revealing the presence of MCP1 and CCR2 in the motor cortex of ALS patients, to elucidate, visualize, and define the timing, location and the extent of immune response in relation to upper motor neuron vulnerability and progressive degeneration in ALS, we developed MCP1-CCR2-hSOD1 G93A mice, an ALS reporter line, in which cells expressing MCP1 and CCR2 are genetically labeled by monomeric red fluorescent protein-1 and enhanced green fluorescent protein, respectively. In the motor cortex of MCP1-CCR2-hSOD1 G93A mice, unlike in the spinal cord, there was an early increase in the numbers of MCP1+ cells, which displayed microglial morphology and selectively expressed microglia markers. Even though fewer CCR2+ cells were present throughout the motor cortex, they were mainly infiltrating monocytes. Interestingly, MCP1+ cells were found in close proximity to the apical dendrites and cell bodies of corticospinal motor neurons (CSMN), further implicating the importance of their cellular interaction to neuronal pathology. Similar findings were observed in the motor cortex of ALS patients, where MCP1+ microglia were especially in close proximity to the degenerating apical dendrites of Betz cells. Our findings reveal that the intricate cellular interplay between immune cells and upper motor neurons observed in the motor cortex of ALS mice is indeed recapitulated in ALS patients. We generated and characterized a novel model system, to study the cellular and molecular basis of this close cellular interaction and how that relates to motor neuron vulnerability and progressive degeneration in

  15. Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury

    Science.gov (United States)

    Coburn, Luke; Lopez, Hender; Schouwenaar, Irin-Maya; Yap, Alpha S.; Lobaskin, Vladimir; Gomez, Guillermo A.

    2018-03-01

    Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.

  16. Preliminary experience on early mechanical recanalization of middle cerebral artery for acute ischemic stroke and literature review

    International Nuclear Information System (INIS)

    Bai Weixing; Li Tianxiao; Zhu Liangfu; Xue Jiangyu; Wang Ziliang

    2012-01-01

    Objective: To evaluate the feasibility,efficacy and complication of early middle cerebral artery (MCA) mechanical recanalization (MER) for treatment of acute ischemic stroke. Methods: Seven cases undergone MER of MCA for the treatment of acute cerebral infarct were retrospectively reviewed and analyzed, including the etiology, mechanism, Qureshi grading scale, location and size of infarcts, NIHSS score of pre and post procedure, endovascular technique and complications. Referring to the literature, the indications of MCA recanalization were further identified. Results: A total of 7 cases with mean age of 48 yrs were reviewed, which included 3 cases of atherosclerotic thrombosis and 4 embolic cases with pre NIHSS score ranging from 3 to 22. Mechanical recanalization succeeded in 6 cases, but 2 cases of cardiogenic embolism died of intracranial hemorrhage postoperatively. Favorable clinical outcomes were achieved in 4 cases whereas 1 deteriorated. Overall complications seemed to be consistent with literatures reviewed. Conclusions: Early MER of MCA may benefit to a certain subset of acute ischemia stroke patients, however, embolic cases, elder patients and those with severe neurologic deficits are often accompanied by higher complications and unfavorable outcome. (authors)

  17. Comparison of airway pressure release ventilation to conventional mechanical ventilation in the early management of smoke inhalation injury in swine.

    Science.gov (United States)

    Batchinsky, Andriy I; Burkett, Samuel E; Zanders, Thomas B; Chung, Kevin K; Regn, Dara D; Jordan, Bryan S; Necsoiu, Corina; Nguyen, Ruth; Hanson, Margaret A; Morris, Michael J; Cancio, Leopoldo C

    2011-10-01

    The role of airway pressure release ventilation in the management of early smoke inhalation injury has not been studied. We compared the effects of airway pressure release ventilation and conventional mechanical ventilation on oxygenation in a porcine model of acute respiratory distress syndrome induced by wood smoke inhalation. Prospective animal study. Government laboratory animal intensive care unit. Thirty-three Yorkshire pigs. Smoke inhalation injury. Anesthetized female Yorkshire pigs (n = 33) inhaled room-temperature pine-bark smoke. Before injury, the pigs were randomized to receive conventional mechanical ventilation (n = 15) or airway pressure release ventilation (n = 12) for 48 hrs after smoke inhalation. As acute respiratory distress syndrome developed (PaO2/Fio2 ratio conventional mechanical ventilation for 48 hrs and served as time controls. Changes in PaO2/Fio2 ratio, tidal volume, respiratory rate, mean airway pressure, plateau pressure, and hemodynamic variables were recorded. Survival was assessed using Kaplan-Meier analysis. PaO2/Fio2 ratio was lower in airway pressure release ventilation vs. conventional mechanical ventilation pigs at 12, 18, and 24 hrs (p conventional mechanical ventilation animals between 30 and 48 hrs post injury (p animals between 6 and 48 hrs (p conventional mechanical ventilation and airway pressure release ventilation pigs. In this model of acute respiratory distress syndrome caused by severe smoke inhalation in swine, airway pressure release ventilation-treated animals developed acute respiratory distress syndrome faster than conventional mechanical ventilation-treated animals, showing a lower PaO2/Fio2 ratio at 12, 18, and 24 hrs after injury. At other time points, PaO2/Fio2 ratio was not different between conventional mechanical ventilation and airway pressure release ventilation.

  18. Temperature Dependences of Mechanisms Responsible for the Water-Vapor Continuum Absorption

    Science.gov (United States)

    Ma, Qiancheng

    2014-01-01

    The water-vapor continuum absorption plays an important role in the radiative balance in the Earth's atmosphere. It has been experimentally shown that for ambient atmospheric conditions, the continuum absorption scales quadratically with the H2O number density and has a strong, negative temperature dependence (T dependence). Over the years, there have been three different theoretical mechanisms postulated: far-wings of allowed transition lines, water dimers, and collision-induced absorption. The first mechanism proposed was the accumulation of absorptions from the far-wings of the strong allowed transition lines. Later, absorption by water dimers was proposed, and this mechanism provides a qualitative explanation for the continuum characters mentioned above. Despite the improvements in experimental data, at present there is no consensus on which mechanism is primarily responsible for the continuum absorption.

  19. Early prediction of the response of breast tumors to neoadjuvant chemotherapy using quantitative MRI and machine learning.

    Science.gov (United States)

    Mani, Subramani; Chen, Yukun; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Bhave, Sandeep R; Welch, E Brian; Levy, Mia A; Yankeelov, Thomas E

    2011-01-01

    The ability to predict early in the course of treatment the response of breast tumors to neoadjuvant chemotherapy can stratify patients based on response for patient-specific treatment strategies. Currently response to neoadjuvant chemotherapy is evaluated based on physical exam or breast imaging (mammogram, ultrasound or conventional breast MRI). There is a poor correlation among these measurements and with the actual tumor size when measured by the pathologist during definitive surgery. We tested the feasibility of using quantitative MRI as a tool for early prediction of tumor response. Between 2007 and 2010 twenty consecutive patients diagnosed with Stage II/III breast cancer and receiving neoadjuvant chemotherapy were enrolled on a prospective imaging study. Our study showed that quantitative MRI parameters along with routine clinical measures can predict responders from non-responders to neoadjuvant chemotherapy. The best predictive model had an accuracy of 0.9, a positive predictive value of 0.91 and an AUC of 0.96.

  20. Analysis of early mesothelial cell responses to Staphylococcus epidermidis isolated from patients with peritoneal dialysis-associated peritonitis.

    Science.gov (United States)

    McGuire, Amanda L; Mulroney, Kieran T; Carson, Christine F; Ram, Ramesh; Morahan, Grant; Chakera, Aron

    2017-01-01

    The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised. We systematically investigated the early mesothelial cell response to clinical and reference isolates of S. epidermidis using primary mesothelial cells and the mesothelial cell line Met-5A. Using an unbiased whole genome microarray, followed by a targeted panel of genes known to be involved in the human antibacterial response, we identified 38 differentially regulated genes (adj. p-value peritonitis. This study provides new insights into early mesothelial cell responses to infection with S. epidermidis, and confirms the importance of validating findings in primary mesothelial cells.

  1. Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

    International Nuclear Information System (INIS)

    Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Muskhelishvili, Levan; Rodriguez-Juarez, Rocio; Kovalchuk, Olga; Han Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.

    2007-01-01

    Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G 1 to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen

  2. Prior Puma Lentivirus Infection Modifies Early Immune Responses and Attenuates Feline Immunodeficiency Virus Infection in Cats

    Directory of Open Access Journals (Sweden)

    Wendy S. Sprague

    2018-04-01

    Full Text Available We previously showed that cats that were infected with non-pathogenic Puma lentivirus (PLV and then infected with pathogenic feline immunodeficiency virus (FIV (co-infection with the host adapted/pathogenic virus had delayed FIV proviral and RNA viral loads in blood, with viral set-points that were lower than cats infected solely with FIV. This difference was associated with global CD4+ T cell preservation, greater interferon gamma (IFN-γ mRNA expression, and no cytotoxic T lymphocyte responses in co-infected cats relative to cats with a single FIV infection. In this study, we reinforced previous observations that prior exposure to an apathogenic lentivirus infection can diminish the effects of acute infection with a second, more virulent, viral exposure. In addition, we investigated whether the viral load differences that were observed between PLV/FIV and FIV infected cats were associated with different immunocyte phenotypes and cytokines. We found that the immune landscape at the time of FIV infection influences the infection outcome. The novel findings in this study advance our knowledge about early immune correlates and documents an immune state that is associated with PLV/FIV co-infection that has positive outcomes for lentiviral diseases.

  3. HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

    Science.gov (United States)

    Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

    2017-08-01

    Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

  4. EXPERIMENTAL INFECTION WITH Toxocara cati IN PIGS: MIGRATORY PATTERN AND PATHOLOGICAL RESPONSE IN EARLY PHASE

    Directory of Open Access Journals (Sweden)

    Irma Estela Sommerfelt

    2014-07-01

    Full Text Available Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi. Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

  5. The predictive value of early maladaptive schemas in paranoid responses to social stress.

    Science.gov (United States)

    Sundag, Johanna; Ascone, Leonie; Lincoln, Tania M

    2018-01-01

    Social stress and negatively valenced cognitive representations of the self (self-schemas) play an important role in the formation of delusions. However, it has not been investigated whether and which self-schemas explain paranoid responses to social stress. Building on the framework of schema theory, the aim of this study was thus to investigate whether more pronounced early maladaptive schemas (EMSs) were associated with increased paranoid ideation after a social stress induction in patients with persecutory delusions (PD). Patients with PD (n = 20) and healthy controls (n = 40) were assessed for EMSs with the Young Schema Questionnaire. They were then exposed to a social stress situation in which they were socially excluded in a Cyberball paradigm. Prior to and after the social stress induction, paranoid symptoms were assessed. Patients with PD responded with a stronger increase in paranoia and revealed a significantly higher EMS total score compared to the healthy controls. As expected, higher increases in paranoia following the social stress were accounted for by higher EMS total scores. Exploratory analyses showed that particularly the specific EMSs Defectiveness/Shame and Enmeshment/Undeveloped Self were associated with the increase in paranoia. EMSs are associated with stress-related symptom increases in patients with PD. It thus seems worthwhile to further investigate the relevance of specific schemas for paranoia. The findings also suggest that addressing EMSs in psychological treatment of patients with PD holds potential. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Genetic evidence for the association between the early growth response 3 (EGR3 gene and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    Full Text Available Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3 gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3 showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016 and allele frequency distribution (P = 0.009. Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012; a significant difference was found for the common haplotype AG (P = 0.0005. Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001. In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis.

  7. Children's parasympathetic reactivity to specific emotions moderates response to intervention for early-onset aggression.

    Science.gov (United States)

    Gatzke-Kopp, Lisa M; Greenberg, Mark; Bierman, Karen

    2015-01-01

    Following theories that individual differences in respiratory sinus arrhythmia (RSA) denote differential sensitivity to environmental influences, this study examines whether differences in RSA reactivity to specific emotional challenges predict differential response to intervention. We present data from a randomized clinical trial of a targeted intervention for early onset aggression. In collaboration with a high-risk urban school district, 207 kindergarten children (73% African American, 66% male), identified by their teachers as having high levels of aggressive and disruptive behavior, were recruited. All children received a universal social-emotional curriculum. One hundred children were randomly assigned to an additional intervention consisting of weekly peer-based social skills training. Complete RSA data were available for 139 of the children. Teacher-reported externalizing symptoms and emotion regulation in 1st grade (post intervention) were examined controlling for baseline levels. First-grade peer nominations of aggressive behavior, controlling for baseline nominations, were also examined as outcomes. No effect of resting RSA was found. However, greater reactivity to anger was associated with higher externalizing symptoms and lower emotion regulation skills in 1st grade relative to low reactive children. Lower reactivity to fear was associated with greater improvement over time, an effect that was enhanced in the targeted intervention condition. Results suggest that measures of affective reactivity may provide insight into children's capacity to benefit from different types of interventions.

  8. Important Factors for Early Market Microgrids: Demand Response and Plug-in Electric Vehicle Charging

    Science.gov (United States)

    White, David Masaki

    Microgrids are evolving concepts that are growing in interest due to their potential reliability, economic and environmental benefits. As with any new concept, there are many unresolved issues with regards to planning and operation. In particular, demand response (DR) and plug-in electric vehicle (PEV) charging are viewed as two key components of the future grid and both will likely be active technologies in the microgrid market. However, a better understanding of the economics associated with DR, the impact DR can have on the sizing of distributed energy resource (DER) systems and how to accommodate and price PEV charging is necessary to advance microgrid technologies. This work characterizes building based DR for a model microgrid, calculates the DER systems for a model microgrid under DR through a minimization of total cost, and determines pricing methods for a PEV charging station integrated with an individual building on the model microgrid. It is shown that DR systems which consist only of HVAC fan reductions provide potential economic benefits to the microgrid through participation in utility DR programs. Additionally, peak shaving DR reduces the size of power generators, however increasing DR capacity does not necessarily lead to further reductions in size. As it currently stands for a microgrid that is an early adopter of PEV charging, current installation costs of PEV charging equipment lead to a system that is not competitive with established commercial charging networks or to gasoline prices for plug-in hybrid electric vehicles (PHEV).

  9. The effects of early experience on subsequent feeding responses in the Tegu, Tupinambis teguixin (Squamata : Teiidae).

    Science.gov (United States)

    Punzo, F

    2003-01-01

    The purpose of this study was to assess the effects of early feeding experiences on subsequent responses to prey in the tegu, Tupinambis teguixin. Five-day old lizards were exposed to the odors of various prey and control substances on cotton-tipped applicators with the tongue-flick attack score (TFAS) chosen as the dependent variable. Each lizard was exposed to four stimuli: two controls (deionised water and cologne), and extracts from a mouse Mus musculus, and a lizard Ameiva ameiva, in a repeated measures, randomized block design, receiving one stimulus training session / day over a 40-day period. Tongue-flicks directed toward the applicator were counted over a 1 min period as well as the amount of time that elapsed from the first tongue flick to any bite that may have occurred. Live neonatal mice (but not A. ameiva), offered on a weekly basis, were used as a food source for tegus over a 10-month period. After 10 months, tegus were exposed to applicators containing control odors as well as those containing extracts from mice and lizards (A. ameiva). Mouse extracts elicited significantly higher TFAS as compared to those elicited by A. ameiva or control odors, suggesting that prey odors encountered in the environment shortly after hatching can influence prey preferences by these lizards later in life. These results also indicate that tegu lizards can learn to use specific odor cues associated with naturally occurring prey as releasers for subsequent hunting behaviors.

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

    Science.gov (United States)

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

    2013-08-01

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

  11. Monitoring early tumor response to drug therapy with diffuse optical tomography

    Science.gov (United States)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  12. Proteinase-activated receptors - mediators of early and delayed normal tissue radiation responses

    International Nuclear Information System (INIS)

    Hauer-Jensen, M.

    2003-01-01

    Proteinase-activated receptors (PARs) are G-protein coupled receptors that are activated by proteolytic exposure of a receptor-tethered ligand. The discovery of this receptor family represents one of the most intriguing recent developments in signal transduction. PARs are involved in the regulation of many normal and pathophysiological processes, notably inflammatory and fibroproliferative responses to injury. Preclinical studies performed in our laboratory suggest that proteinase-activated receptor-1 (PAR-1) plays a critical role in the mechanism of chronicity of radiation fibrosis, while proteinase-activated receptor-2 (PAR-2) may mediate important fibroproliferative responses in irradiated intestine. Specifically, activation of PAR-1 by thrombin, and PAR-2 by pancreatic trypsin and mast cell proteinases, appears to be involved in acute radiation-induced inflammation, as well as in subsequent extracellular matrix deposition, leading to the development of intestinal wall fibrosis and clinical complications. Pharmacological modulators of PAR-1 or PAR-2 expression or activation would be potentially useful as preventive or therapeutic agents in patients who receive radiation therapy, especially if blockade could be targeted to specific tissues or cellular compartments

  13. Quantum mechanics its early development and the road to entanglement and beyond

    CERN Document Server

    Steward, Edward G

    2012-01-01

    This book provides the reader with an explanation of the origin and establishment of quantum mechanics together with a descriptive survey of developments up to the present day. The mathematics is presented in a digestible form yet following the original approach. This second edition presents two new chapters to supplement and extend the first edition material. "Interpretations of Quantum Mechanics" surveys a wide range of current topics, including the multiverse, 't Hooft's ideas for a deterministic local field theory, a summary of the de Broglie-Bohm pilot-wave theory and Anthony Valentini's development of it, and speculative concluding comments on the way ahead.

  14. InteractInteraction mechanism of emergency response in geological hazard perception and risk management: a case study in Zhouqu county

    Science.gov (United States)

    Qi, Yuan; Zhao, Hongtao

    2017-04-01

    China is one of few several natural disaster prone countries, which has complex geological and geographical environment and abnormal climate. On August 8, 2010, a large debris flow disaster happened in Zhouqu Country, Gansu province, resulting in more than 1700 casualties and more than 200 buildings damaged. In order to percept landslide and debris flow, an early warning system was established in the county. Spatial information technologies, such as remote sensing, GIS, and GPS, play core role in the early warning system, due to their functions in observing, analyzing, and locating geological disasters. However, all of these spatial information technologies could play an important role only guided by the emergency response mechanism. This article takes the establishment of Zhouqu Country's Disaster Emergency Response Interaction Mechanism (DERIM) as an example to discuss the risk management of country-level administrative units. The country-level risk management aims to information sharing, resources integration, integrated prevention and unified command. Then, nine subsystems support DERIM, which included disaster prevention and emergency data collection and sharing system, joint duty system, disaster verification and evaluation system, disaster consultation system, emergency warning and information release system, emergency response system, disaster reporting system, plan management system, mass prediction and prevention management system. At last, an emergency command platform in Zhouqu Country built up to realize DERIM. The core mission of the platform consists of daily management of disaster, monitoring and warning, comprehensive analysis, information release, consultation and decision-making, emergency response, etc. Five functional modules, including module of disaster information management, comprehensive monitoring module (geological monitoring, meteorological monitoring, water conservancy and hydrological monitoring), alarm management module, emergency

  15. Mechanisms of Egg Yolk Formation and Implications on Early Life History of White Perch (Morone americana.

    Directory of Open Access Journals (Sweden)

    Justin Schilling

    Full Text Available The three white perch (Morone americana vitellogenins (VtgAa, VtgAb, VtgC were quantified accurately and precisely in the liver, plasma, and ovary during pre-, early-, mid-, and post-vitellogenic oocyte growth using protein cleavage-isotope dilution mass spectrometry (PC-IDMS. Western blotting generally mirrored the PC-IDMS results. By PC-IDMS, VtgC was quantifiable in pre-vitellogenic ovary tissues and VtgAb was quantifiable in pre-vitellogenic liver tissues however, neither protein was detected by western blotting in these respective tissues at this time point. Immunohistochemistry indicated that VtgC was present within pre-vitellogenic oocytes and localized to lipid droplets within vitellogenic oocytes. Affinity purification coupled to tandem mass spectrometry using highly purified VtgC as a bait protein revealed a single specific interacting protein (Y-box binding protein 2a-like [Ybx2a-like] that eluted with suramin buffer and confirmed that VtgC does not bind the ovary vitellogenin receptors (LR8 and Lrp13. Western blotting for LR8 and Lrp13 showed that both receptors were expressed during vitellogenesis with LR8 and Lrp13 expression highest in early- and mid-vitellogenesis, respectively. The VtgAa within the ovary peaked during post-vitellogenesis, while VtgAb peaked during early-vitellogenesis in both white perch and the closely related striped bass (M. saxatilis. The VtgC was steadily accumulated by oocytes beginning during pre-vitellogenesis and continued until post-vitellogenesis and its composition varies widely between striped bass and white perch. In striped bass, the VtgC accounted for 26% of the vitellogenin-derived egg yolk, however in the white perch it comprised only 4%. Striped bass larvae have an extended developmental window and these larvae have yolk stores that may enable them to survive in the absence of food for twice as long as white perch after hatch. Thus, the VtgC may play an integral role in providing nutrients to

  16. Multi-scale mechanical response of freeze-dried collagen scaffolds for tissue engineering applications.

    Science.gov (United States)

    Offeddu, Giovanni S; Ashworth, Jennifer C; Cameron, Ruth E; Oyen, Michelle L

    2015-02-01

    Tissue engineering has grown in the past two decades as a promising solution to unresolved clinical problems such as osteoarthritis. The mechanical response of tissue engineering scaffolds is one of the factors determining their use in applications such as cartilage and bone repair. The relationship between the structural and intrinsic mechanical properties of the scaffolds was the object of this study, with the ultimate aim of understanding the stiffness of the substrate that adhered cells experience, and its link to the bulk mechanical properties. Freeze-dried type I collagen porous scaffolds made with varying slurry concentrations and pore sizes were tested in a viscoelastic framework by macroindentation. Membranes made up of stacks of pore walls were indented using colloidal probe atomic force microscopy. It was found that the bulk scaffold mechanical response varied with collagen concentration in the slurry consistent with previous studies on these materials. Hydration of the scaffolds resulted in a more compliant response, yet lesser viscoelastic relaxation. Indentation of the membranes suggested that the material making up the pore walls remains unchanged between conditions, so that the stiffness of the scaffolds at the scale of seeded cells is unchanged; rather, it is suggested that thicker pore walls or more of these result in the increased moduli for the greater slurry concentration conditions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Responses of Phospholipase D and Antioxidant System to Mechanical Wounding in Postharvest Banana Fruits

    Directory of Open Access Journals (Sweden)

    Li Li

    2017-01-01

    Full Text Available Banana fruits are susceptible to mechanical damage. The present study was to investigate the responses of phospholipase D (PLD and antioxidant system to mechanical wounding in postharvest banana fruits. During 16 d storage at 25°C and 90% relative humidity, PLD activity in wounded fruits was significantly higher than that in control (without artificial wounding fruits. The higher value of PLD mRNA was found in wounded fruits than in control. PLD mRNA expression reached the highest peak on day 4 in both groups, but it was 2.67 times in wounded fruits compared to control at that time, indicating that PLD gene expression was activated in response to wounding stress. In response to wounding stress, the higher lipoxygenase (LOX activity was observed and malondialdehyde (MDA production was accelerated. The activities of antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT, peroxidase (POD, and ascorbate peroxidase (APX in wounded fruits were significantly higher than those in control. The concentrations of reactive oxygen species (ROS such as superoxide anion (O2•- and hydrogen peroxide (H2O2 in fruits increased under mechanical wounding. The above results provided a basis for further investigating the mechanism of postharvest banana fruits adapting to environmental stress.

  18. Early immune response patterns to pathogenic bacteria are associated to increased risk of lower respiratory infections in children

    DEFF Research Database (Denmark)

    Vissing, N. H.; Larsen, Jeppe Madura; Rasmussen, Mette Annelie

    2014-01-01

    Neonatal colonisation of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood (1). Therefore, we hypothesized that children developing LRI have an abnormal immune response to pathogenic bacteria in infancy. We aimed...... to characterise the systemic immune response to pathogenic bacteria at the age of 6 months and study the association with incidence of LRI during the first 3 years of life....

  19. RNA-seq analysis of early hepatic response to handling and confinement stress in rainbow trout.

    Directory of Open Access Journals (Sweden)

    Sixin Liu

    Full Text Available Fish under intensive rearing conditions experience various stressors which have negative impacts on survival, growth, reproduction and fillet quality. Identifying and characterizing the molecular mechanisms underlying stress responses will facilitate the development of strategies that aim to improve animal welfare and aquaculture production efficiency. In this study, we used RNA-seq to identify transcripts which are differentially expressed in the rainbow trout liver in response to handling and confinement stress. These stressors were selected due to their relevance in aquaculture production. Total RNA was extracted from the livers of individual fish in five tanks having eight fish each, including three tanks of fish subjected to a 3 hour handling and confinement stress and two control tanks. Equal amount of total RNA of six individual fish was pooled by tank to create five RNA-seq libraries which were sequenced in one lane of Illumina HiSeq 2000. Three sequencing runs were conducted to obtain a total of 491,570,566 reads which were mapped onto the previously generated stress reference transcriptome to identify 316 differentially expressed transcripts (DETs. Twenty one DETs were selected for qPCR to validate the RNA-seq approach. The fold changes in gene expression identified by RNA-seq and qPCR were highly correlated (R(2 = 0.88. Several gene ontology terms including transcription factor activity and biological process such as glucose metabolic process were enriched among these DETs. Pathways involved in response to handling and confinement stress were implicated by mapping the DETs to reference pathways in the KEGG database.Raw RNA-seq reads have been submitted to the NCBI Short Read Archive under accession number SRP022881.All customized scripts described in this paper are available from Dr. Guangtu Gao or the corresponding author.

  20. IgD, cyclooxygenase-2 and ribosomal protein S6-PS240 immune response in a case of early psoriasis

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2018-02-01

    Full Text Available Psoriasis is an inflammatory skin disease. Five classic types of psoriasis have been defined: plaque, inverse, pustular, guttate, and erythrodermic. The early psoriasis immunologic skin immune response is not well understood. Here we aim to show an immune and cell signaling response in a case of early psoriasis. A 56 year old female presented with a desquamative lesion on her right leg. A skin biopsy for hematoxylin and eosin (H&E and immunohistochemistry (IHC staining was taken. The diagnosis indicated early psoriasis, and IHC showed positive IgD staining in the epidermal corneal layer, as well as positive staining with ribosomal protein S6-pS240 (RIBO in the hyperproliferative epidermis. Cyclooxygenase-2 (COX-2 was also very positive in the granular layer in spots, at the basement membrane zone of the skin and in the inflammatory infiltrate in the dermis subjacent to hyperproliferative psoriatic areas. In an early case of psoriasis, we confirmed the presence of IgD, RIBO and COX-2. Each molecule seems to be playing a role in inflammation and intracellular signaling pathways in early psoriasis. The role of IgD is unknown, and this case brings to light the complexity of the pathologic changes occurring in early psoriatic lesions.

  1. Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus.

    Science.gov (United States)

    Stephens, Andrew D; Banigan, Edward J; Adam, Stephen A; Goldman, Robert D; Marko, John F

    2017-07-07

    The cell nucleus must continually resist and respond to intercellular and intracellular mechanical forces to transduce mechanical signals and maintain proper genome organization and expression. Altered nuclear mechanics is associated with many human diseases, including heart disease, progeria, and cancer. Chromatin and nuclear envelope A-type lamin proteins are known to be key nuclear mechanical components perturbed in these diseases, but their distinct mechanical contributions are not known. Here we directly establish the separate roles of chromatin and lamin A/C and show that they determine two distinct mechanical regimes via micromanipulation of single isolated nuclei. Chromatin governs response to small extensions (<3 μm), and euchromatin/heterochromatin levels modulate the stiffness. In contrast, lamin A/C levels control nuclear strain stiffening at large extensions. These results can be understood through simulations of a polymeric shell and cross-linked polymer interior. Our results provide a framework for understanding the differential effects of chromatin and lamin A/C in cell nuclear mechanics and their alterations in disease. © 2017 Stephens et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  2. Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.

    Directory of Open Access Journals (Sweden)

    Kai Weng

    Full Text Available Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1 as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.

  3. Modeling for mechanical response of CICC by hierarchical approach and ABAQUS simulation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.X.; Wang, X.; Gao, Y.W., E-mail: ywgao@lzu.edu.cn; Zhou, Y.H.

    2013-11-15

    Highlights: • We develop an analytical model based on the hierarchical approach of classical wire rope theory. • The numerical model is set up through ABAQUS to verify and enhance the theoretical model. • We calculate two concerned mechanical response: global displacement–load curve and local axial strain distribution. • Elastic–plasticity is the main character in loading curve, and the friction between adjacent strands plays a significant role in the distribution map. -- Abstract: An unexpected degradation frequently occurs in superconducting cable (CICC) due to the mechanical response (deformation) when suffering from electromagnetic load and thermal load during operation. Because of the cable's hierarchical twisted configuration, it is difficult to quantitatively model the mechanical response. In addition, the local mechanical characteristics such as strain distribution could be hardly monitored via experimental method. To address this issue, we develop an analytical model based on the hierarchical approach of classical wire rope theory. This approach follows the algorithm advancing successively from n + 1 stage (e.g. 3 × 3 × 5 subcable) to n stage (e.g. 3 × 3 subcable). There are no complicated numerical procedures required in this model. Meanwhile, the numerical model is set up through ABAQUS to verify and enhance the theoretical model. Subsequently, we calculate two concerned mechanical responses: global displacement–load curve and local axial strain distribution. We find that in the global displacement–load curve, the elastic–plasticity is the main character, and the higher-level cable shows enhanced nonlinear characteristics. As for the local distribution, the friction among adjacent strands plays a significant role in this map. The magnitude of friction strongly influences the regularity of the distribution at different twisted stages. More detailed results are presented in this paper.

  4. Modeling for mechanical response of CICC by hierarchical approach and ABAQUS simulation

    International Nuclear Information System (INIS)

    Li, Y.X.; Wang, X.; Gao, Y.W.; Zhou, Y.H.

    2013-01-01

    Highlights: • We develop an analytical model based on the hierarchical approach of classical wire rope theory. • The numerical model is set up through ABAQUS to verify and enhance the theoretical model. • We calculate two concerned mechanical response: global displacement–load curve and local axial strain distribution. • Elastic–plasticity is the main character in loading curve, and the friction between adjacent strands plays a significant role in the distribution map. -- Abstract: An unexpected degradation frequently occurs in superconducting cable (CICC) due to the mechanical response (deformation) when suffering from electromagnetic load and thermal load during operation. Because of the cable's hierarchical twisted configuration, it is difficult to quantitatively model the mechanical response. In addition, the local mechanical characteristics such as strain distribution could be hardly monitored via experimental method. To address this issue, we develop an analytical model based on the hierarchical approach of classical wire rope theory. This approach follows the algorithm advancing successively from n + 1 stage (e.g. 3 × 3 × 5 subcable) to n stage (e.g. 3 × 3 subcable). There are no complicated numerical procedures required in this model. Meanwhile, the numerical model is set up through ABAQUS to verify and enhance the theoretical model. Subsequently, we calculate two concerned mechanical responses: global displacement–load curve and local axial strain distribution. We find that in the global displacement–load curve, the elastic–plasticity is the main character, and the higher-level cable shows enhanced nonlinear characteristics. As for the local distribution, the friction among adjacent strands plays a significant role in this map. The magnitude of friction strongly influences the regularity of the distribution at different twisted stages. More detailed results are presented in this paper

  5. Exercise improves cognitive responses to psychological stress through enhancement of epigenetic mechanisms and gene expression in the dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Andrew Collins

    Full Text Available We have shown previously that exercise benefits stress resistance and stress coping capabilities. Furthermore, we reported recently that epigenetic changes related to gene transcription are involved in memory formation of stressful events. In view of the enhanced coping capabilities in exercised subjects we investigated epigenetic, gene expression and behavioral changes in 4-weeks voluntarily exercised rats.Exercised and control rats coped differently when exposed to a novel environment. Whereas the control rats explored the new cage for the complete 30-min period, exercised animals only did so during the first 15 min after which they returned to sleeping or resting behavior. Both groups of animals showed similar behavioral responses in the initial forced swim session. When re-tested 24 h later however the exercised rats showed significantly more immobility behavior and less struggling and swimming. If rats were killed at 2 h after novelty or the initial swim test, i.e. at the peak of histone H3 phospho-acetylation and c-Fos induction, then the exercised rats showed a significantly higher number of dentate granule neurons expressing the histone modifications and immediate-early gene induction.Thus, irrespective of the behavioral response in the novel cage or initial forced swim session, the impact of the event at the dentate gyrus level was greater in exercised rats than in control animals. Furthermore, in view of our concept that the neuronal response in the dentate gyrus after forced swimming is involved in memory formation of the stressful event, the observations in exercised rats of enhanced neuronal responses as well as higher immobility responses in the re-test are consistent with the reportedly improved cognitive performance in these animals. Thus, improved stress coping in exercised subjects seems to involve enhanced cognitive capabilities possibly resulting from distinct epigenetic mechanisms in dentate gyrus neurons.

  6. Early stiffening and softening of collagen : interplay of deformation mechanisms in biopolymer networks

    NARCIS (Netherlands)

    Kurniawan, N.A.; Wong, Long Hui; Rajagopalan, Raj

    2012-01-01

    Collagen networks, the main structural/mechanical elements in biological tissues, increasingly serve as biomimetic scaffolds for cell behavioral studies, assays, and tissue engineering, and yet their full spectrum of nonlinear behavior remains unclear. Here, with self-assembled type-I collagen as

  7. Early life exposure to famine and colorectal cancer risk: A role for epigenetic mechanisms

    NARCIS (Netherlands)

    Hughes, L.A.E.; Brandt, P.A. van den; Bruïne, A.P. de; Wouters, K.A.D.; Hulsmans, S.; Spiertz, A.; Goldbohm, R.A.; Goeij, A.F.P.M. de; Herman, J.G.; Weijenberg, M.P.; Engeland, M. van

    2009-01-01

    Background: Exposure to energy restriction during childhood and adolescence is associated with a lower risk of developing colorectal cancer (CRC). Epigenetic dysregulation during this critical period of growth and development may be a mechanism to explain such observations. Within the Netherlands

  8. Children Do Show Negative Priming: Further Evidence for Early Development of an Intact Selective Control Mechanism

    Science.gov (United States)

    Frings, Christian; Feix, Silke; Rothig, Ulrike; Bruser, Charlotte; Junge, Miriam

    2007-01-01

    Reactions to stimuli that were shortly before presented as distractors are usually slowed down; this phenomenon is known as negative priming. Negative priming is an accepted index for tapping into selective control